{ "$schema": "https://peptides101.com/api/compounds", "meta": { "name": "Peptides101 regulatory and evidence tracker", "description": "Legal status and evidence quality for peptides. The two axes are INDEPENDENT: a legal status is not a safety rating, and an evidence tier is not a legal status.", "recordCount": 44, "lastVerified": "2026-08-02", "license": "https://creativecommons.org/licenses/by/4.0/", "attribution": "https://peptides101.com — cite as Peptides101", "funding": "peptides101.com carries no advertising, accepts no sponsorship, sells no products, and earns no commission on anything we write about.", "containsDosingInformation": false, "notes": [ "Legal status describes where a substance sits in FDA's 503A evaluation process. It is not a safety finding and not a statement about whether sale is lawful.", "Evidence tier is assigned by what was ADMINISTERED to humans, never by counting publications. Endogenous-biomarker studies do not count as administration.", "verifiedAt is the date a human last checked the claim against its source. It is deliberately distinct from the source document's own date.", "An evidence tier of 'verification-pending' means we have not finished checking. It is not an assessment and should not be read as one." ] }, "compounds": [ { "slug": "aod-9604", "name": "AOD-9604", "aliases": [ "AOD9604", "Anti-Obesity Drug 9604", "hGH fragment 176-191", "hGH 176-191", "Tyr-hGH(177-191)" ], "url": "https://peptides101.com/compounds/aod-9604", "moleculeNote": "Sold almost universally as 'hGH fragment 176-191', which is not what it is. AOD-9604 is a hexadecapeptide: the C-terminal fragment of human growth hormone spanning residues 177-191 plus an ADDITIONAL TYROSINE residue at the N-terminus that is not present in human GH. It is a synthetic analogue, not a native fragment. This has one consequence worth stating plainly: the endogenous-biomarker trap that inflates the apparent human evidence base for MOTS-c and TB-500 cannot operate here, because AOD-9604 does not occur in the body and cannot be measured as an endogenous analyte. Every human measurement of it is a measurement of an administered drug.", "quickAnswer": "AOD-9604 is not an FDA-approved drug — FDA's approvals database returns no matches for it — and it is not on FDA's 503A bulk drug substances list, appearing instead in FDA's table of substances 'nominated but withdrawn', which records a withdrawal by the nominator rather than any clearance by FDA. Real human data does exist, unusually for a peptide sold this way: six double-blind, placebo-controlled trials run by sponsor Metabolic Pharmaceuticals between 2001 and 2006 dosed roughly 900 adult subjects, of which only the two long-term trials are described by the sponsor's own methods as randomised. But the programme was terminated in 2007 after its 24-week trial failed to induce significant weight loss, no primary report of the long-term efficacy results was ever published in the peer-reviewed literature, and FDA states it has identified serious adverse events that may be associated with AOD-9604, though causality is not clear.", "fdaStatus": { "value": "not-approved", "note": "Not an FDA-approved drug for any indication, and not in active development toward approval. That says nothing about whether it is sold — it is.", "source": { "url": "https://www.fda.gov/drugs/human-drug-compounding/certain-bulk-drug-substances-use-compounding-may-present-significant-safety-risks", "title": "Certain Bulk Drug Substances for Use in Compounding that May Present Significant Safety Risks", "publisher": "FDA", "date": "2026-05-14", "quote": "Bulk drug substances nominated but withdrawn" }, "verifiedAt": "2026-07-16" }, "compoundingStatus": { "value": "withdrawn-from-nomination", "note": "Absent from Categories 1, 2 and 3 in the list updated 2026-05-14 — verified by fetching and text-extracting the document directly. Category 2 contains exactly six substances (Cesium Chloride, Domperidone, Germanium Sesquioxide, Ibutamoren Mesylate, Kisspeptin-10, Quinacrine HCl for intrauterine administration) and AOD-9604 is not among them. The absence is documented, not inferred: FDA's companion safety-risks page lists AOD-9604 under the table heading 'Bulk drug substances nominated but withdrawn', which is what rules out `never-nominated`. The nomination was withdrawn by the nominator. That is not a legalisation event — AOD-9604 did not enter Category 1, is not on the 503A bulks list, and remains non-compoundable. Status moved sideways, not forward. Separately: AOD-9604 is NOT one of the seven substances before the Pharmacy Compounding Advisory Committee on 23-24 July 2026 (those are BPC-157, emideltide/DSIP, epitalon, KPV, MOTS-c, semax and TB-500). No PCAC review of AOD-9604 is scheduled, so readers waiting on a July 2026 decision for this compound are waiting for a meeting that is not about it.", "source": { "url": "https://www.fda.gov/drugs/human-drug-compounding/certain-bulk-drug-substances-use-compounding-may-present-significant-safety-risks", "title": "Certain Bulk Drug Substances for Use in Compounding that May Present Significant Safety Risks", "publisher": "FDA", "date": "2026-05-14", "quote": "Bulk drug substances nominated but withdrawn" }, "verifiedAt": "2026-07-16" }, "evidence": { "tier": "promising-but-unproven", "humanAdministrationChecked": true, "note": "Administration check run and PASSED — the drug was genuinely given to humans. Six double-blind, placebo-controlled trials conducted 2001-2006 by sponsor Metabolic Pharmaceuticals dosed roughly 900 adult subjects: three Phase I/IIa single-dose studies and one Phase IIa multiple-dose study, plus two long-term Phase IIb studies of 12 and 24 weeks. Intravenous route in the two earliest studies, oral thereafter. This is administration of an exogenous synthetic analogue, not endogenous biomarker measurement. ON RANDOMISATION, because it is the key quality marker and the source is internally inconsistent about it: Stier's ABSTRACT says 'Six randomized, double-blind, placebo-controlled trials were performed with AOD9604', but Stier's own METHODS label only the two Phase IIb studies — METAOD005 and METAOD006 — as randomized. METAOD001 and METAOD004 are described as '(double-blind, placebo-controlled, dose escalation)' and METAOD002 and METAOD003 as '(double-blind, placebo-controlled 4 × 4 Latin Square design)', with no randomisation stated for any of the four. We therefore describe all six as double-blind and placebo-controlled, which the methods support, and only the two Phase IIb trials as randomised. Repeating the sponsor's strongest framing in our own voice would be the same deference this record criticises elsewhere. ON REGISTRATION: ClinicalTrials.gov returns ZERO registrations for AOD-9604/AOD9604 (API queried 2026-07-16), but that bare negative reads as concealment and the fuller fact is in our own load-bearing source — Stier states 'The two largest studies (METAOD005 and METAOD006) were registered at the Therapeutic Goods Administration's Clinical Trial Notification (CTN) Scheme in Australia.' The two pivotal trials WERE registered, on the Australian regulator's scheme rather than a US registry. This is the jurisdiction artefact stated positively: the usual 'no registrations therefore no human data' inference is simply wrong for this compound, and so is any vendor claim resting on registry counts in either direction. The tier is 'promising-but-unproven' strictly in this schema's sense — human data exists, efficacy is NOT established — and the word 'promising' should not be read as encouraging. The vocabulary is explicit that this tier includes programmes that were tested and failed, which is what happened here. There is no Phase 3, and AOD-9604 is not an FDA-approved drug (Drugs@FDA, fdaFindings below). We make no claim about approval in other jurisdictions: we hold no source for one, and the obviously relevant regulator for an Australian sponsor — the TGA — was not successfully checked on 2026-07-16. A blank is honest. The honest gap, now narrower than this record previously stated it: Stier 2013 reports SAFETY AND TOLERABILITY ONLY and does not report the efficacy results of the Phase IIb studies. No PRIMARY peer-reviewed trial report of those outcomes appears ever to have been published. The outcomes are nonetheless known — from the sponsor's ASX announcement of 21 February 2007 (not peer-reviewed; its URL is dead and the company is gone) and from peer-reviewed secondary reviews that report it, principally Valentino et al. 2010. The 12-week figures are not reproduced here because they carry dosing. What is verified: a real controlled programme in ~900 humans ran, its 24-week trial failed to induce significant weight loss, and it did not produce an approved drug.", "source": { "url": "https://doi.org/10.4021/jem157w", "title": "Safety and Tolerability of the Hexadecapeptide AOD9604 in Humans", "publisher": "Journal of Endocrinology and Metabolism 3(1-2):7-15", "date": "2013-04-01", "quote": "All studies were performed as double-blind placebo-controlled trials … Approximately 900 adult subjects participated in these 6 clinical trials." }, "verifiedAt": "2026-07-16" }, "fdaApproval": null, "fdaFindings": [ { "finding": "FDA identifies AOD-9604 as posing significant immunogenicity risk for certain routes of administration, with complexities regarding peptide-related impurities and API characterization.", "note": "Note the scope: this finding is about COMPOUNDED DRUGS containing AOD-9604 as a bulk substance — impurity profiles and characterization of the API as supplied — not about the sponsor's pharmaceutical-grade material used in the 2001-2006 trials. A safety record generated under GMP in a controlled trial does not transfer to a compounded or gray-market preparation of the same sequence. Of the substances FDA lists here, AOD-9604 is one of the few given 'significant' rather than plain 'risk' for immunogenicity — FDA's wording for BPC-157, CJC-1295 and epitalon omits that adjective.", "source": { "url": "https://www.fda.gov/drugs/human-drug-compounding/certain-bulk-drug-substances-use-compounding-may-present-significant-safety-risks", "title": "Certain Bulk Drug Substances for Use in Compounding that May Present Significant Safety Risks", "publisher": "FDA", "date": "2026-04-22", "quote": "Compounded drugs containing AOD-9604 may pose significant risk for immunogenicity for certain routes of administration and may have complexities with regard to peptide-related impurities and API characterization." }, "verifiedAt": "2026-07-16" }, { "finding": "FDA states it lacks sufficient information to know whether AOD-9604 would cause harm when administered to humans.", "note": "This sits in genuine, unresolved tension with the evidence record above, and we are recording the tension rather than smoothing it. FDA says it has 'no, or only limited' safety information; a sponsor-funded pooled analysis reports six placebo-controlled trials in ~900 subjects. Both statements are documented. READ THE SCOPING CLAUSE CAREFULLY, because it is not what it is for BPC-157. FDA's BPC-157 entry on this same page says it has identified no, or only limited, safety-related information 'for the proposed routes of administration'. The AOD-9604 sentence contains no such qualifier — FDA states flatly that it has identified no, or only limited, safety-related information. Re-verified against the page text on 2026-07-16. An earlier version of this note offered route-scoping as one candidate explanation for the tension; the document does not support that reading, and it is withdrawn. Only the immunogenicity sentence above is route-scoped. We still do NOT know which of the remaining explanations is correct — the nomination may never have put the trial data before the agency; unpublished sponsor data is not data FDA holds; the trials were never registered on a US registry and were published, in part, in a journal not indexed in PubMed; or FDA may weigh a sponsor's own unpublished-efficacy programme differently than the sponsor does. Anyone asserting a single explanation is guessing. What must not be done with this quote is either available distortion: it is not FDA conceding AOD-9604 is untested, and it is not FDA calling it dangerous.", "source": { "url": "https://www.fda.gov/drugs/human-drug-compounding/certain-bulk-drug-substances-use-compounding-may-present-significant-safety-risks", "title": "Certain Bulk Drug Substances for Use in Compounding that May Present Significant Safety Risks", "publisher": "FDA", "date": "2026-04-22", "quote": "FDA has identified no, or only limited, safety-related information. Therefore, the agency lacks sufficient information to know whether the drug would cause harm when administered to humans." }, "verifiedAt": "2026-07-16" }, { "finding": "FDA states that the bulk drug substances it lists as 'nominated but withdrawn' — the table AOD-9604 appears in — were previously in category 2 and were withdrawn by the nominators, not by FDA.", "note": "The sentence the market gets backwards, quoted as printed (including FDA's own subject-verb disagreement). It establishes three things at once, and the third is the one that matters. First, AOD-9604 was nominated — this is the documentary basis for `withdrawn-from-nomination` rather than `never-nominated`. Second, it was in category 2, the significant-safety-risk category, before it left. Third, the actor was the NOMINATOR. FDA did not clear AOD-9604, did not reverse its safety assessment, and did not move it anywhere; a private party stopped asking. FDA's retention of the substance on this safety-risks page, with its risk text intact, after the withdrawal is the point: the assessment survived the nomination. Withdrawal removed the request, not the finding.", "source": { "url": "https://www.fda.gov/drugs/human-drug-compounding/certain-bulk-drug-substances-use-compounding-may-present-significant-safety-risks", "title": "Certain Bulk Drug Substances for Use in Compounding that May Present Significant Safety Risks", "publisher": "FDA", "date": "2026-04-22", "quote": "This list of bulk drug substances previously in category 2 of the interim policies were withdrawn by the nominators." }, "verifiedAt": "2026-07-16" }, { "finding": "Drugs@FDA, FDA's database of approved drug products, returns no matches for AOD-9604. There is no approved application for AOD-9604 for any indication or route.", "note": "The quote is the API's verbatim response body, not prose about it — the only honest way to cite an absence. Queried on generic name, active-ingredient name and brand name; all three return the same. The claim is deliberately narrow: it establishes that no approval EXISTS, not that FDA reviewed and refused one. Those are different facts and only the first is in evidence — we found no record that AOD-9604 was ever the subject of an NDA. This finding is load-bearing on THIS record in a way it is not on the others here. Everywhere else in this set, 'no approval' is unsurprising because there is no clinical programme. AOD-9604 has one — six controlled trials, ~900 subjects — which makes the inference 'a real trial programme, therefore it must be approved somewhere' available and wrong. A programme that ran and stopped leaves exactly this trace: trials in the literature, nothing in the approvals database.", "source": { "url": "https://api.fda.gov/drug/drugsfda.json?search=openfda.generic_name:\"aod-9604\"+OR+products.active_ingredients.name:\"AOD-9604\"+OR+openfda.generic_name:\"aod9604\"&limit=5", "title": "Drugs@FDA — approved drug products database, queried for AOD-9604 (openFDA)", "publisher": "FDA", "date": "2026-07-16", "quote": "No matches found!" }, "verifiedAt": "2026-07-16" } ], "safetySignals": [ { "signal": "FDA has identified serious adverse events that may be associated with AOD-9604, with causality not established.", "note": "The most important sentence on this record and the least usable, in both directions. FDA does not say what the events were, how many, by what route, or from what source. We attempted corroboration and failed: the openFDA FAERS API returns NO matching records for medicinalproduct 'AOD-9604' or 'AOD9604' (queried 2026-07-16), so unlike BPC-157 — where the PCAC briefing document itemises two FAERS reports — we cannot characterise these events at all. The 'serious adverse events' language does imply some human exposure occurred, which the trial programme independently establishes; it does NOT follow that the events came from those trials. 'Causality is not clear' is FDA's own qualifier and must travel with the claim. Treated correctly, this is an unresolved signal: not evidence of harm, and not evidence of safety.", "source": { "url": "https://www.fda.gov/drugs/human-drug-compounding/certain-bulk-drug-substances-use-compounding-may-present-significant-safety-risks", "title": "Certain Bulk Drug Substances for Use in Compounding that May Present Significant Safety Risks", "publisher": "FDA", "date": "2026-04-22", "quote": "FDA has also identified serious adverse events that may be associated with AOD-9604, though causality is not clear." }, "verifiedAt": "2026-07-16" }, { "signal": "The sponsor's pooled analysis of all six trials reports no treatment-related serious adverse events, directly contradicting FDA's serious-adverse-event statement.", "note": "Recorded as a CONTRADICTION, not as reassurance. Read the byline: Vos and Kenley were employed by Metabolic Pharmaceuticals, which funded all six trials, and the paper thanks the sponsor for that funding. A manufacturer-authored pooled safety analysis of its own unregistered trials, published in a journal not indexed in PubMed, is the weakest possible evidence against a regulator's adverse-event finding — and it is routinely the single citation vendor pages use to call AOD-9604 'clinically proven safe'. Note also what the sentence actually says: no serious events RELATED TO INTAKE, a causality judgement made by the sponsor. It does not say no serious events occurred. The two findings are not reconcilable from public documents, and we are not reconciling them.", "source": { "url": "https://doi.org/10.4021/jem157w", "title": "Safety and Tolerability of the Hexadecapeptide AOD9604 in Humans", "publisher": "Journal of Endocrinology and Metabolism 3(1-2):7-15", "date": "2013-04-01", "quote": "In none of the studies did a withdrawal or serious adverse event occur related to intake of AOD9604." }, "verifiedAt": "2026-07-16" } ], "faqs": [ { "question": "Is AOD-9604 legal in 2026?", "answer": "AOD-9604 is not on FDA's 503A bulk drug substances list — the list of substances that may lawfully be used in pharmacy compounding — as of the list updated 14 May 2026, and it appears in none of that list's three categories. It is not an FDA-approved drug and is not a component of one. Absence from the list is not a permission: it means AOD-9604 has not been found appropriate for compounding, not that it has been cleared for it.", "source": { "url": "https://www.fda.gov/media/94155/download", "title": "Bulk Drug Substances Nominated for Use in Compounding Under Section 503A of the Federal Food, Drug, and Cosmetic Act", "publisher": "FDA", "date": "2026-05-14" }, "verifiedAt": "2026-07-16" }, { "question": "Did AOD-9604 become legal when FDA removed it from Category 2?", "answer": "No. FDA did not remove AOD-9604 from Category 2 — the nominator withdrew the nomination. FDA's own page states of the substances in that table: 'This list of bulk drug substances previously in category 2 of the interim policies were withdrawn by the nominators.' A withdrawal moves a substance sideways rather than toward legality: AOD-9604 did not enter Category 1, did not join FDA's 503A bulk drug substances list, and remains outside the set of substances that may lawfully be used in compounding. FDA's safety assessment of AOD-9604 also survived the withdrawal — the agency still publishes it, and still states that compounded drugs containing AOD-9604 may pose significant risk for immunogenicity for certain routes of administration.", "source": { "url": "https://www.fda.gov/drugs/human-drug-compounding/certain-bulk-drug-substances-use-compounding-may-present-significant-safety-risks", "title": "Certain Bulk Drug Substances for Use in Compounding that May Present Significant Safety Risks", "publisher": "FDA", "date": "2026-04-22", "quote": "This list of bulk drug substances previously in category 2 of the interim policies were withdrawn by the nominators." }, "verifiedAt": "2026-07-16" }, { "question": "Did FDA approve AOD-9604?", "answer": "No. Drugs@FDA, FDA's database of approved drug products, returns 'No matches found!' for AOD-9604 when queried by generic name, active-ingredient name and brand name (checked 16 July 2026). There is no approved application for AOD-9604 for any indication or by any route. Drugs@FDA is a United States database, so this establishes non-approval in the US and nothing about other jurisdictions — we hold no source on those and are not going to guess. This is worth stating plainly because AOD-9604 does have a genuine clinical history — six controlled trials in roughly 900 adults, conducted 2001-2006 — which makes it tempting to assume an approval followed. None did in the US; the development programme was terminated in 2007 after its 24-week trial failed to induce significant weight loss.", "source": { "url": "https://api.fda.gov/drug/drugsfda.json?search=openfda.generic_name:\"aod-9604\"+OR+products.active_ingredients.name:\"AOD-9604\"+OR+openfda.generic_name:\"aod9604\"&limit=5", "title": "Drugs@FDA — approved drug products database, queried for AOD-9604 (openFDA)", "publisher": "FDA", "date": "2026-07-16", "quote": "No matches found!" }, "verifiedAt": "2026-07-16" }, { "question": "Is there any human evidence that AOD-9604 works?", "answer": "Human data exists, but it does not establish that AOD-9604 works. Six double-blind, placebo-controlled trials were conducted between 2001 and 2006 by the Australian sponsor Metabolic Pharmaceuticals, and a pooled analysis authored in part by that sponsor's own employees reports that 'All studies were performed as double-blind placebo-controlled trials' and that 'Approximately 900 adult subjects participated in these 6 clinical trials.' That same paper's methods describe only the two long-term Phase IIb studies as randomised, so the sponsor abstract's 'six randomized' framing overstates its own methods section. The paper reports safety and tolerability only. No primary report of the efficacy results of the two long-term trials, of 12 and 24 weeks, appears ever to have been published in the peer-reviewed literature — those outcomes are known only from the sponsor's 2007 announcement to the Australian Securities Exchange and from peer-reviewed reviews citing it. No trial in the programme was registered on ClinicalTrials.gov, though the same paper states the two largest studies were registered on the Australian Therapeutic Goods Administration's Clinical Trial Notification scheme — the absence is from the US registry, not from all registries. No Phase 3 trial was ever conducted. What is established is that a real controlled programme in roughly 900 humans ran and did not produce an approved drug.", "source": { "url": "https://doi.org/10.4021/jem157w", "title": "Safety and Tolerability of the Hexadecapeptide AOD9604 in Humans", "publisher": "Journal of Endocrinology and Metabolism 3(1-2):7-15", "date": "2013-04-01", "quote": "Approximately 900 adult subjects participated in these 6 clinical trials." }, "verifiedAt": "2026-07-16" }, { "question": "Why was AOD-9604 discontinued?", "answer": "Because it did not work well enough in its largest trial. A 2010 peer-reviewed review in Clinical Pharmacology & Therapeutics reports that 'Development of this drug was terminated in 2007 because the drug failed to induce significant weight loss in a 24-week trial of 536 subjects.' That review is not itself a trial report: it attributes the termination to the sponsor Metabolic Pharmaceuticals' own announcement to the Australian Securities Exchange of 21 February 2007, which stated that the Phase 2B results did not support the drug's commercial viability as a treatment for obesity and that development for that condition was terminated. The sponsor's pooled safety paper describes that 24-week trial as enrolling 502 rather than 536 subjects; we cannot reconcile the two figures and assert neither as our own. The direction of the result is not in dispute. This is the fact most often missing from pages selling AOD-9604: it is not an untested compound awaiting its trial, it is a compound that had its trial.", "source": { "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC3136748/", "title": "Central and Peripheral Molecular Targets for Anti-Obesity Pharmacotherapy", "publisher": "Clinical Pharmacology & Therapeutics 87(6):652-662", "date": "2010-05-05", "quote": "Development of this drug was terminated in 2007 because the drug failed to induce significant weight loss in a 24-week trial of 536 subjects." }, "verifiedAt": "2026-07-16" }, { "question": "Is AOD-9604 safe?", "answer": "Unknown, and the two available documents disagree. FDA states that it 'has also identified serious adverse events that may be associated with AOD-9604, though causality is not clear', that it lacks sufficient information to know whether the drug would cause harm when administered to humans, and that compounded drugs containing AOD-9604 may pose significant risk for immunogenicity for certain routes of administration. FDA does not say what those adverse events were, and openFDA's adverse event database returns no matching reports for AOD-9604, so they cannot be characterised further from public records. Against this, a pooled analysis of the 2001-2006 trials — authored in part by employees of the company that funded them — reports that no serious adverse event related to intake occurred in any of the six studies. Neither document resolves the other, and a safety record generated with pharmaceutical-grade material under a sponsor's control does not transfer to a compounded or grey-market preparation of the same sequence.", "source": { "url": "https://www.fda.gov/drugs/human-drug-compounding/certain-bulk-drug-substances-use-compounding-may-present-significant-safety-risks", "title": "Certain Bulk Drug Substances for Use in Compounding that May Present Significant Safety Risks", "publisher": "FDA", "date": "2026-04-22", "quote": "FDA has also identified serious adverse events that may be associated with AOD-9604, though causality is not clear." }, "verifiedAt": "2026-07-16" }, { "question": "Is AOD-9604 banned in sport?", "answer": "Yes. AOD-9604 is named in the World Anti-Doping Agency's 2026 Prohibited List, which came into effect on 1 January 2026, at section S2.2.3: 'Growth hormone (GH), its analogues and fragments including, but not limited to: … growth hormone fragments, e.g. AOD-9604 and hGH 176-191.' Section S2 substances are prohibited at all times, both in- and out-of-competition, and the list states that all prohibited substances in that class are non-Specified Substances. Being prohibited in sport is a sport-eligibility fact only: it is not a finding that AOD-9604 is effective, and WADA prohibits substances regardless of whether their claimed effects have been demonstrated.", "source": { "url": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "title": "World Anti-Doping Code International Standard — Prohibited List 2026", "publisher": "World Anti-Doping Agency", "date": "2026-01-01", "quote": "Growth hormone (GH), its analogues and fragments including, but not limited to: … growth hormone fragments, e.g. AOD-9604 and hGH 176-191" }, "verifiedAt": "2026-07-16" } ] }, { "slug": "ara-290", "name": "ARA-290", "aliases": [ "Cibinetide", "ARA 290", "ARA290", "ARA290 Acetate", "pHSBP", "pHBSP", "pyroglutamate helix B surface peptide" ], "url": "https://peptides101.com/compounds/ara-290", "moleculeNote": "An 11-amino-acid peptide derived from the B-helix of erythropoietin. The NCT06626971 registration gives the full chemical name as 'L-Pyroglutamyl-L-glutamyl-L-glutaminyl-L-leucyl-L-glutamyl-L-arginyl-L-alanyl-L-leucyl-L-asparaginyl-L-seryl-L-serine' — eleven residues, beginning with pyroglutamate. The NCT02039687 registration lists 'pHSBP, Cibinetide' as other names for it; the literature more often writes pHBSP, for pyroglutamate helix B surface peptide, and both spellings are aliased above so a reader searching either lands here. SALT FORM IS A LIVE DISAMBIGUATION, as it is for BPC-157. FDA's National Drug Code directory carries this substance under two different generic names — 'ARA290' and 'ARA290 Acetate' — with the same active-ingredient name, CIBINETIDE. A vial labelled 'ARA-290' does not by itself say which was in it.", "quickAnswer": "ARA-290 (cibinetide) is not an FDA-approved drug for any indication — it has no record in Drugs@FDA — and it may not lawfully be used in pharmacy compounding under section 503A, because FDA places 'Cibinetide (ARA-290)' in Category 3 of its bulk drug substances list, the category for substances nominated without adequate support, rather than on the 503A bulks list itself. Unlike most peptides sold in this market, ARA-290 has genuinely been administered to humans: a randomised, quadruple-masked, placebo-controlled phase 2b trial of 64 subjects with sarcoidosis-associated small nerve fiber loss, sponsored by Araim Pharmaceuticals (NCT02039687), completed in February 2015 and posted results. That trial's primary endpoint was a surrogate — corneal nerve fiber area — and the placebo-corrected change reached statistical significance in only one of its three ARA 290 arms, with the confidence intervals for the other two crossing zero. No phase 3 trial of ARA-290 has been registered, ClinicalTrials.gov lists no active or recruiting study of it, and the most recently registered trial — a nine-patient phase 2 study in diabetic macular oedema — is recorded as terminated for the stated reason 'Expiry of study drug - no replacement available.'", "fdaStatus": { "value": "not-approved", "note": "Not an FDA-approved drug for any indication, in any country this record could identify, and not in active development toward approval. THE QUERY WAS RUN THE WAY THIS PROJECT LEARNED TO RUN IT. Drugs@FDA was searched five ways — products.active_ingredients.name:\"CIBINETIDE\", openfda.generic_name:\"cibinetide\", openfda.substance_name:\"CIBINETIDE\", and bare free-text for both 'cibinetide' and 'ARA-290'. All five returned NOT_FOUND. Because an empty openfda block can manufacture a false negative, a positive control was run in the same request shape on the same field: products.active_ingredients.name:\"SEMAGLUTIDE\" returns six applications. The field works. The substance is absent. WHY NOT 'investigational', WHICH IS WHAT THE PUBLICATION RECORD SUPERFICIALLY SUGGESTS. The bar in this vocabulary is active development by an identifiable sponsor with registered trials, and the registry does not meet it. ClinicalTrials.gov returns three interventional studies of this molecule and nothing else. None is recruiting or active. The only one sponsored by Araim Pharmaceuticals (NCT02039687) has an actual completion date of February 2015. A Karolinska-led study in prediabetes and type 2 diabetes (NCT01933529) sits at status UNKNOWN with its last update posted in September 2015. And the most recently registered one (NCT06626971) was posted in October 2024 for a trial that had already run in 2016-2017, and is recorded as TERMINATED with the stated reason 'Expiry of study drug - no replacement available.' Read that last point carefully, because a pipeline sorting by 'last updated' will read 2024 as recent activity. It is not new work. It is a retrospective registration of an old trial whose drug supply ran out.", "source": { "url": "https://api.fda.gov/drug/drugsfda.json?search=products.active_ingredients.name:%22CIBINETIDE%22&limit=5", "title": "Drugs@FDA — query for CIBINETIDE as a product active ingredient (openFDA drug/drugsfda)", "publisher": "FDA", "date": "2026-07-31", "quote": "{ \"error\": { \"code\": \"NOT_FOUND\", \"message\": \"No matches found!\" } }" }, "verifiedAt": "2026-08-02" }, "compoundingStatus": { "value": "category-3", "note": "Verified by downloading fda.gov/media/94155/download with a browser user-agent and text-extracting it locally on 2026-08-02. The document is headed 'Updated May 14, 2026'. 'Cibinetide (ARA-290)' occurs exactly once in it, on its own bullet under the Category 3 heading, alphabetically between 'Chromium glycinate' and 'Coenzyme Q50'. It is not in Category 1 and not in Category 2 — Category 2 holds exactly six substances, and this is not one of them. WHAT CATEGORY 3 DOES AND DOES NOT MEAN. FDA's own heading defines it: nominated without adequate support. It is a finding about the NOMINATION, not about the molecule — it does not say ARA-290 is dangerous and it does not say ARA-290 is ineffective. What it does mean, operationally, is unchanged by the category: ARA-290 is not on the 503A bulks list, so a bulk drug substance that is neither the subject of a USP monograph nor a component of an approved drug may not be used in 503A compounding. Category 3 is inside the document; the bulks list is the document's subject. Being listed in a category is not being on the list.", "source": { "url": "https://www.fda.gov/media/94155/download", "title": "Bulk Drug Substances Nominated for Use in Compounding Under Section 503A of the Federal Food, Drug, and Cosmetic Act", "publisher": "FDA", "date": "2026-05-14", "quote": "503A Category 3: Bulk Drug Substances Nominated Without Adequate Support … • Cibinetide (ARA-290)" }, "verifiedAt": "2026-08-02" }, "evidence": { "tier": "promising-but-unproven", "humanAdministrationChecked": true, "note": "ADMINISTRATION CHECK RUN, NOT ASSUMED — and it passes, which on this site is the less common outcome. The full NCT02039687 record was opened on 2026-08-02 and read down to the results section. Intervention type DRUG, name 'ARA 290', other names 'pHSBP, Cibinetide'; three experimental arms administered subcutaneously versus a placebo comparator described as 'Formulation buffer'; allocation RANDOMIZED, quadruple masking (participant, care provider, investigator, outcomes assessor); enrolment 64 ACTUAL; lead sponsor Araim Pharmaceuticals, Inc.; status COMPLETED with actual primary completion 2015-01 and actual completion 2015-02; results first posted 2017-01-18; hasResults true, with a participant flow table, a baseline table, outcome measures and an adverse-event table all populated. ARA-290 was GIVEN to these people. It was not measured as an endogenous biomarker, which is the trap that reduces MOTS-c and TB-500 from an apparent five human RCTs to an actual zero. FOUR MORE HUMAN ADMINISTRATION STUDIES were checked at abstract level on 2026-08-02 and each states administration explicitly. PMIDs are given so each is independently locatable: Heij et al. 2012, PMID 23168581 (22 sarcoidosis patients with small fiber neuropathy symptoms, randomised double-blind, intravenous, ARA 290 n=12 vs placebo n=10); Dahan et al. 2013, PMID 24136731 (blinded placebo-controlled, 28 days of subcutaneous administration in patients with documented small nerve fiber loss and damage); Brines et al. 2015, PMID 25387363 (phase 2 in type 2 diabetes with painful neuropathy, self-administered subcutaneously over 28 days versus placebo); Lois et al. 2020, PMID 32674280 (phase 2 in diabetic macular oedema, nine patients recruited, self-administered subcutaneously over 12 weeks). A healthy-volunteer study also administered it: Cerit et al. 2015, PMID 26431906, N=36, double-blind randomised parallel-group versus placebo. State the limit honestly — for these five the abstract was read, not the full text; only NCT02039687 was read at record level. WHY THE TIER IS NOT HIGHER. 'Promising-but-unproven' is the tier this vocabulary reserves for a real human signal that is not established, explicitly including programmes that were tested and stopped. Three things keep it here. (1) The phase 2b primary endpoint was a SURROGATE — corneal nerve fiber area, which the authors themselves frame as a surrogate endpoint for disease modification, not as a clinical outcome. (2) It separated from placebo in only one of the three active arms: per Culver et al. 2017 the placebo-corrected 95% confidence intervals for the other two both cross zero. (3) There is no phase 3. No registered phase 3 trial of this molecule exists, and the pain endpoint the indication would actually turn on did not reach significance against placebo in that trial's own reporting (P = 0.157 in the arm the authors highlight). SCOPE. This tier attaches to sarcoidosis-associated small fiber neuropathy and the adjacent neuropathy endpoints that were actually studied. It does not travel to tissue repair, injury recovery, longevity or any other use ARA-290 is marketed for; the literature since 2018 on those questions is overwhelmingly rodent and in-vitro.", "source": { "url": "https://clinicaltrials.gov/study/NCT02039687", "title": "A Double Blind, Placebo Controlled Phase 2 Dose Ranging Study of the Effects of ARA 290 on Corneal Nerve Fiber Density and Neuropathic Symptoms of Subjects With Sarcoidosis (NCT02039687)", "publisher": "ClinicalTrials.gov", "date": "2017-04-18" }, "verifiedAt": "2026-08-02" }, "fdaApproval": null, "fdaFindings": [ { "finding": "FDA lists 'Cibinetide (ARA-290)' in Category 3 of the 503A bulk drug substances list — bulk drug substances nominated without adequate support — in the version updated 14 May 2026. It is not in Category 1 and not in Category 2, and it is not on the 503A bulks list itself.", "note": "The single most surprising fact on this record, and it inverts the site's usual assumption for a peptide of this profile. ARA-290 is normally described in the consumer market as having no regulatory footprint at all. It has one: somebody nominated it for pharmacy compounding, and FDA's disposition was to place it among the nominations made without adequate supporting information. Note what that does NOT license in either direction — Category 3 is not a safety finding against the molecule, and it is not a step toward availability. The substance is not on the bulks list, which is the only list that permits 503A compounding.", "source": { "url": "https://www.fda.gov/media/94155/download", "title": "Bulk Drug Substances Nominated for Use in Compounding Under Section 503A of the Federal Food, Drug, and Cosmetic Act", "publisher": "FDA", "date": "2026-05-14", "quote": "503A Category 3: Bulk Drug Substances Nominated Without Adequate Support … • Cibinetide (ARA-290)" }, "verifiedAt": "2026-08-02" }, { "finding": "Cibinetide does not appear in Drugs@FDA. Queries against the product active-ingredient name, the openFDA generic name, the openFDA substance name, and bare free text for both 'cibinetide' and 'ARA-290' all return no matches.", "note": "A negative result is only worth as much as the query behind it, so the query is stated in full and a positive control was run alongside it: the identical request shape with SEMAGLUTIDE in place of CIBINETIDE returns six applications. openFDA's `meta.last_updated` for drug/drugsfda was 2026-07-31 at the time of checking. This is the check that a previous pass on a different compound in this library got wrong by querying only the openfda block, which is frequently empty.", "source": { "url": "https://api.fda.gov/drug/drugsfda.json?search=products.active_ingredients.name:%22CIBINETIDE%22&limit=5", "title": "Drugs@FDA — query for CIBINETIDE as a product active ingredient (openFDA drug/drugsfda)", "publisher": "FDA", "date": "2026-07-31", "quote": "{ \"error\": { \"code\": \"NOT_FOUND\", \"message\": \"No matches found!\" } }" }, "verifiedAt": "2026-08-02" }, { "finding": "Cibinetide DOES appear in FDA's National Drug Code directory — as three BULK INGREDIENT listings from active-ingredient suppliers, none of them a finished drug product. The labelers are Qingdao Biopeptek Co., Ltd (marketing start 2022-01-03), DARMERICA, LLC (2026-01-13) and Nanjing Chengong Pharmaceutical Co., Ltd. (2026-02-25). Two of the three list the substance as 'ARA290 Acetate' and one as 'ARA290'; all three name the active ingredient CIBINETIDE.", "note": "Recorded because 'it has an FDA NDC number' is the argument this market reaches for next, and it does not mean what it is used to mean. Every one of these records carries marketing_category BULK INGREDIENT, product_type BULK INGREDIENT, and finished: false. Listing a bulk substance in the NDC directory is a registration and listing obligation for the establishment; FDA does not review a bulk-ingredient listing for safety or effectiveness and no approval attaches to it. The number identifies a barrel of powder, not a medicine. The DATES are the interesting part. Two of the three listings began in the first two months of 2026 — the API supply chain organising itself around this molecule at exactly the point the consumer peptide market discovered it, and years after the clinical programme stopped.", "source": { "url": "https://api.fda.gov/drug/ndc.json?search=cibinetide&limit=5", "title": "National Drug Code Directory — listings whose active ingredient is CIBINETIDE (openFDA drug/ndc)", "publisher": "FDA", "date": "2026-07-31" }, "verifiedAt": "2026-08-02" }, { "finding": "Cibinetide and ARA-290 do not appear anywhere on FDA's page documenting bulk drug substances that may present significant safety risks, including its table of substances 'nominated but withdrawn'.", "note": "Fetched and text-extracted 2026-08-02: zero occurrences of 'cibinetide', 'ARA-290' or 'ARA 290'. Recorded to close two misreadings at once. It means FDA has published no specific safety risk for this substance under the compounding programme — which is not the same as a finding of safety, and on the evidence of this record is better read as the silence that follows a nomination FDA judged inadequately supported. It also means ARA-290's history is NOT the BPC-157 history: it was not in Category 2 and its nomination was not withdrawn. It is in Category 3 on its own terms.", "source": { "url": "https://www.fda.gov/drugs/human-drug-compounding/certain-bulk-drug-substances-use-compounding-may-present-significant-safety-risks", "title": "Certain Bulk Drug Substances for Use in Compounding that May Present Significant Safety Risks", "publisher": "FDA", "date": "2026-05-14", "quote": "Bulk drug substances nominated but withdrawn" }, "verifiedAt": "2026-08-02" } ], "safetySignals": [ { "signal": "In the posted results of the 64-subject phase 2b sarcoidosis trial, 3 of the 46 subjects at risk across the three ARA 290 arms had a serious adverse event, against 0 of 16 on placebo. The serious events recorded were syncope, headache, chest tightness, shortness of breath, small bowel enteritis and suicidal ideation. Non-serious treatment-emergent events were reported at a similar rate in both, 37 of 46 on ARA 290 and 12 of 16 on placebo, and were predominantly gastrointestinal.", "note": "Counts taken from the registration's own adverse-event table on 2026-08-02, with a frequency threshold of 0 and a stated time frame of the treatment period plus follow-up. Aggregated deliberately across the three active arms: the table breaks the events out by arm, and reproducing that breakdown would publish a dose-to-outcome mapping, which this site does not do. READ THE NUMBERS FOR WHAT THEY ARE. Six serious events in three subjects, in a trial of 64 people with an inflammatory multisystem disease, is not a safety signal established against placebo — the trial is far too small to separate anything at that rate, and the registration posts no statistical comparison of adverse events. It is recorded here because 'ARA-290 has no reported adverse events' is a claim that circulates, and it is false against the sponsor's own filing. Note also the participant flow: 3 of 46 subjects in the active arms did not complete, against 0 of 16 on placebo.", "source": { "url": "https://clinicaltrials.gov/study/NCT02039687", "title": "A Double Blind, Placebo Controlled Phase 2 Dose Ranging Study of the Effects of ARA 290 on Corneal Nerve Fiber Density and Neuropathic Symptoms of Subjects With Sarcoidosis (NCT02039687)", "publisher": "ClinicalTrials.gov", "date": "2017-04-18" }, "verifiedAt": "2026-08-02" }, { "signal": "In the phase 2 diabetic macular oedema trial, the authors reported that no serious adverse events or reactions and no anti-cibinetide antibodies were observed, and concluded that the 12-week course was safe.", "note": "Included as the counterweight, with its limits stated rather than implied. Nine patients were recruited and eight completed; there was no control arm; and the corresponding registration (NCT06626971) records the study as TERMINATED. A safety conclusion drawn from eight completers in an uncontrolled, terminated study establishes almost nothing about a population — its real value is narrower and genuinely useful: this is the only study on this record that looked for antibodies to the peptide and reported the result. Immunogenicity is the risk FDA repeatedly raises for injected peptides of this size, and here somebody actually measured it, in eight people.", "source": { "url": "https://pubmed.ncbi.nlm.nih.gov/32674280/", "title": "A Phase 2 Clinical Trial on the Use of Cibinetide for the Treatment of Diabetic Macular Edema (J Clin Med 2020;9:2225)", "publisher": "PubMed", "date": "2020-07-14", "quote": "No serious adverse events/reactions or anti-cibinetide antibodies were seen. … The cibinetide 12-week course was safe." }, "verifiedAt": "2026-08-02" } ], "faqs": [ { "question": "Is ARA-290 FDA-approved?", "answer": "No. ARA-290, whose international nonproprietary name is cibinetide, has no record in Drugs@FDA — searches of FDA's application database for CIBINETIDE as a product active ingredient, as an openFDA generic name, as an openFDA substance name, and as bare free text for both 'cibinetide' and 'ARA-290' all return no matches, while the identical query run as a control on an approved peptide returns its applications. There is no approved indication, no prescribing information and no brand name, because there is no approved product. One thing that is easy to misread: cibinetide DOES appear in FDA's National Drug Code directory, but only as bulk-ingredient listings from active-ingredient suppliers, each flagged in FDA's own data as an unfinished BULK INGREDIENT. An NDC number for a bulk substance is a listing obligation, not an approval.", "source": { "url": "https://api.fda.gov/drug/drugsfda.json?search=products.active_ingredients.name:%22CIBINETIDE%22&limit=5", "title": "Drugs@FDA — query for CIBINETIDE as a product active ingredient (openFDA drug/drugsfda)", "publisher": "FDA", "date": "2026-07-31", "quote": "{ \"error\": { \"code\": \"NOT_FOUND\", \"message\": \"No matches found!\" } }" }, "verifiedAt": "2026-08-02" }, { "question": "Can a compounding pharmacy legally make ARA-290?", "answer": "Not under section 503A. ARA-290 is not on FDA's 503A bulk drug substances list, and a bulk drug substance that is neither the subject of a USP monograph nor a component of an FDA-approved drug must be on that list to be used in 503A compounding. What makes ARA-290 unusual among the peptides sold in this market is that it is not simply absent from FDA's document: it is named in it. The list updated 14 May 2026 carries the entry 'Cibinetide (ARA-290)' under the heading '503A Category 3: Bulk Drug Substances Nominated Without Adequate Support'. Read that precisely. Category 3 is a finding about the nomination — that it did not come with enough information for FDA to evaluate the substance — not a finding that the substance is unsafe, and not a step toward availability. Being in a category on this document is not the same as being on the bulks list, and only the bulks list permits compounding.", "source": { "url": "https://www.fda.gov/media/94155/download", "title": "Bulk Drug Substances Nominated for Use in Compounding Under Section 503A of the Federal Food, Drug, and Cosmetic Act", "publisher": "FDA", "date": "2026-05-14", "quote": "503A Category 3: Bulk Drug Substances Nominated Without Adequate Support … • Cibinetide (ARA-290)" }, "verifiedAt": "2026-08-02" }, { "question": "Is there human evidence that ARA-290 works for small fiber neuropathy?", "answer": "There is real human data and it is not conclusive. The largest study is a phase 2b, 28-day randomised trial of 64 subjects with sarcoidosis-associated small nerve fiber loss and neuropathic pain, reported by Culver et al. in 2017. Its primary endpoint was a surrogate — corneal nerve fiber area — and the reported result was arm-dependent: 'The placebo-corrected mean change from baseline CNFA (μm2) at day 28 was 109 (95% confidence interval [CI], -429, 647), 697 (159, 1236; P = 0.012), and 431 (-130, 992) in the [lowest], [intermediate] and [highest] arms, respectively.' Two of those three confidence intervals cross zero. On pain, the endpoint a treatment would have to move, the authors reported that pain improved significantly in all groups including placebo, and that the placebo-corrected decrease in subjects with moderate-to-severe pain carried P = 0.157 in the arm they highlight — not a statistically significant separation. The authors' own conclusion was that 'Cibinetide significantly increased small nerve fiber abundance in the cornea and skin, consistent with a disease modifying effect', and their stated purpose was in part to support corneal nerve fiber area as a surrogate endpoint for future trials. No phase 3 trial followed. The arm strengths are replaced with bracketed descriptors above under this site's no-dosing policy; nothing in the finding depends on the figures.", "source": { "url": "https://pubmed.ncbi.nlm.nih.gov/28475703/", "title": "Cibinetide Improves Corneal Nerve Fiber Abundance in Patients With Sarcoidosis-Associated Small Nerve Fiber Loss and Neuropathic Pain (Invest Ophthalmol Vis Sci 2017;58:BIO52-BIO60)", "publisher": "PubMed", "date": "2017-05-01" }, "verifiedAt": "2026-08-02" }, { "question": "Is ARA-290 still in clinical development in 2026?", "answer": "No active development is visible in the trial registry. ClinicalTrials.gov holds three interventional studies of ARA-290 and none is recruiting or active. The only one sponsored by Araim Pharmaceuticals, the phase 2b sarcoidosis trial NCT02039687, has an actual completion date of February 2015. A Karolinska-led study in prediabetes and type 2 diabetes, NCT01933529, sits at status UNKNOWN with its last update posted in September 2015. The third and most recently registered, NCT06626971, is a phase 2 trial of ARA290 in diabetic macular oedema run by the Belfast Health and Social Care Trust with Araim as a collaborator; it is recorded as TERMINATED, and the registration states the reason in its own words: 'Expiry of study drug - no replacement available.' That registration was first posted in October 2024, which can look like recent activity — but the trial itself started in April 2016 and completed in August 2017, so the 2024 date is a retrospective registration, not new work. No phase 3 trial of ARA-290 is registered.", "source": { "url": "https://clinicaltrials.gov/study/NCT06626971", "title": "A Phase II Clinical Trial on the Use of ARA 290 for the Treatment of Diabetic Macular Oedema (NCT06626971)", "publisher": "ClinicalTrials.gov", "date": "2024-10-04", "quote": "Expiry of study drug - no replacement available." }, "verifiedAt": "2026-08-02" }, { "question": "Was ARA-290 ever tested in people with diabetes?", "answer": "Yes, in two small studies, neither of which established anything. Brines et al. reported a phase 2 study in 2015 in which subjects with type 2 diabetes and painful neuropathy self-administered ARA 290 or placebo subcutaneously over 28 days and were followed for a further month; the authors reported improvement in HbA1c and lipid profiles and a significant improvement in neuropathic symptoms on the PainDetect questionnaire, and framed their own conclusion as a hypothesis rather than a result — ARA 290 'may benefit both metabolic control and neuropathy in subjects with type 2 diabetes and deserves continued clinical evaluation.' Separately, a phase 2 trial in diabetic macular oedema recruited nine patients, of whom eight completed, and reported no improvement in the primary or main secondary measures — best corrected visual acuity, central retinal thickness, central retinal sensitivity or tear production. A registered study in prediabetes and type 2 diabetes at the Karolinska Institutet, NCT01933529, has never reported results and its registration status is UNKNOWN.", "source": { "url": "https://pubmed.ncbi.nlm.nih.gov/25387363/", "title": "ARA 290, a nonerythropoietic peptide engineered from erythropoietin, improves metabolic control and neuropathic symptoms in patients with type 2 diabetes (Mol Med 2015;20:658-66)", "publisher": "PubMed", "date": "2015-03-13", "quote": "These observations suggest that ARA 290 may benefit both metabolic control and neuropathy in subjects with type 2 diabetes and deserves continued clinical evaluation." }, "verifiedAt": "2026-08-02" }, { "question": "Is ARA-290 banned in sport?", "answer": "The 2026 WADA Prohibited List does not name ARA-290 or cibinetide. Downloaded and text-extracted on 2 August 2026, the document returns zero hits for 'ARA', '290' and 'cibinetide'. What it does contain is an open-ended class that an athlete would need to consider: section S2.1, 'ERYTHROPOIETINS (EPO) AND AGENTS AFFECTING ERYTHROPOIESIS', is prefaced 'Including, but not limited to:', and subsection S2.1.5 reads in full 'Innate repair receptor agonists, e.g. asialo EPO; carbamylated EPO (CEPO).' The relevance is that ARA-290's own sponsor-filed trial registration describes the drug as 'A small peptide that activates the innate repair receptor'. Whether a substance that is not named falls inside an open-ended class is a determination for anti-doping authorities and not one this record makes — an athlete subject to a WADA-compliant programme should put the question to their anti-doping organisation rather than infer an answer from the absence of a name.", "source": { "url": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "title": "World Anti-Doping Code International Standard: Prohibited List 2026", "publisher": "World Anti-Doping Agency", "date": "2026-01-01", "quote": "S2.1.5 Innate repair receptor agonists, e.g. asialo EPO; carbamylated EPO (CEPO)." }, "verifiedAt": "2026-08-02" }, { "question": "Has ARA-290 been shown to help with injury recovery or tissue repair?", "answer": "Not in humans. Every trial in which ARA-290 has been administered to people studied neuropathy or an eye condition: sarcoidosis-associated small fiber neuropathy in a randomised pilot reported by Heij et al. in 2012 and again by Dahan et al. in 2013, the 64-subject phase 2b reported by Culver et al. in 2017, type 2 diabetic neuropathy in Brines et al. 2015, diabetic macular oedema in Lois et al. 2020, and emotional processing in 36 healthy volunteers in Cerit et al. 2015. None of them studied wound healing, tendon or ligament injury, muscle recovery or athletic performance. The tissue-repair framing comes from the mechanism — the earliest of those trials describes ARA 290 as 'a peptide designed to activate the innate repair receptor that arrests injury and initiates cytoprotection, antiinflammation and healing' — and from a large animal and in-vitro literature. A described mechanism is a reason to run a trial, not a result from one.", "source": { "url": "https://pubmed.ncbi.nlm.nih.gov/23168581/", "title": "Safety and efficacy of ARA 290 in sarcoidosis patients with symptoms of small fiber neuropathy: a randomized, double-blind pilot study (Mol Med 2012;18:1430-6)", "publisher": "PubMed", "date": "2012-11-15", "quote": "ARA 290 (a peptide designed to activate the innate repair receptor that arrests injury and initiates cytoprotection, antiinflammation and healing) reduces allodynia in preclinical neuropathy models." }, "verifiedAt": "2026-08-02" } ] }, { "slug": "bpc-157", "name": "BPC-157", "aliases": [ "Body Protection Compound 157", "PL 14736", "Bepecin", "BPC-157 acetate" ], "url": "https://peptides101.com/compounds/bpc-157", "moleculeNote": "A synthetic pentadecapeptide derived from a partial sequence of human gastric juice protein BPC. FDA evaluates two related substances: BPC-157 (free base) and BPC-157 acetate.", "quickAnswer": "BPC-157 is not approved as a drug in any country, is not on FDA's 503A bulks list, and may not lawfully be used in 503A pharmacy compounding; FDA staff proposed not adding BPC-157 (free base) or BPC-157 acetate to that list ahead of the Pharmacy Compounding Advisory Committee meeting of 23-24 July 2026. In that evaluation FDA reported a lack of evidence of effectiveness for ulcerative colitis — the only use it agreed to evaluate — identified no study administering BPC-157 to humans by the oral, subcutaneous, nasal or transdermal routes it is sold for, and considers the substance not well-characterized.", "fdaStatus": { "value": "not-approved", "note": "Not an FDA-approved drug for any indication, and not in active development toward approval. That says nothing about whether it is sold — it is.", "source": { "url": "https://www.fda.gov/media/193343/download", "title": "BPC-157-Related Bulk Drug Substances — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, July 23-24, 2026", "publisher": "FDA", "date": "2026-07-23" }, "verifiedAt": "2026-07-16" }, "compoundingStatus": { "value": "withdrawn-from-nomination", "note": "Absent from Categories 1, 2 and 3 in the list updated 2026-05-14 — verified by fetching and text-extracting the document directly. It left Category 2 because the nominators withdrew the nominations, not because it moved toward legality. It did not enter Category 1, it is not on the 503A bulks list, and it remains non-compoundable. Widely reported as 'removed from Category 2, access is coming' — that framing is backwards.", "source": { "url": "https://www.fda.gov/media/193343/download", "title": "BPC-157-Related Bulk Drug Substances — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, July 23-24, 2026", "publisher": "FDA", "date": "2026-07-23" }, "verifiedAt": "2026-07-16" }, "evidence": { "tier": "promising-but-unproven", "humanAdministrationChecked": true, "note": "The tier label reads more generously than this record supports, so read the note, not the badge. 'Promising-but-unproven' is assigned only because human data EXISTS — the tier vocabulary reserves it for programmes with a human signal that were tested and were not established, explicitly including ones that failed. This is one that failed. FDA identified five clinical studies that administered BPC-157 to humans, and among them a single randomised controlled trial: Ruenzi et al. 2005, reported only as a meeting abstract, which did not show a benefit. The decisive gap is ROUTE, not count. FDA found no study administering BPC-157 by any route it is actually sold for — oral, subcutaneous, nasal or transdermal. The five studies FDA counted used rectal enema (24 healthy subjects, and approximately 26 subjects with UC), intra-articular injection (17 subjects with knee pain), intravesical injection (12 subjects with interstitial cystitis) and IV infusion (2 healthy subjects). None of those is how anyone buys it. On ClinicalTrials.gov FDA retrieved a single phase 1 study in healthy subjects in Mexico (NCT02637284). State only what FDA states about it: subjects 'were to receive' oral BPC-157, 'The estimated enrollment was 42 subjects. There are no results posted, and we were unable to find an associated published study.' Planned is not conducted, and an estimated enrolment is not an enrolment.", "source": { "url": "https://www.fda.gov/media/193343/download", "title": "BPC-157-Related Bulk Drug Substances — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, July 23-24, 2026", "publisher": "FDA", "date": "2026-07-23", "quote": "Our search of the public medical literature in PubMed and Embase yielded five clinical studies that utilized BPC-157." }, "verifiedAt": "2026-07-16" }, "fdaApproval": null, "fdaFindings": [ { "finding": "FDA staff propose not adding BPC-157 to the 503A Bulks List, ahead of the Pharmacy Compounding Advisory Committee meeting on 23-24 July 2026.", "note": "A staff proposal is not a final determination. The briefing document states: 'The FDA will not issue a final determination on the issues at hand until input from the advisory committee process has been considered and all reviews have been finalized.'", "source": { "url": "https://www.fda.gov/media/193343/download", "title": "BPC-157-Related Bulk Drug Substances — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, July 23-24, 2026", "publisher": "FDA", "date": "2026-07-23", "quote": "Accordingly, we propose not adding BPC-157 (free base) or BPC-157 acetate to the 503A Bulks List." }, "verifiedAt": "2026-07-16" }, { "finding": "BPC-157 was nominated for ulcerative colitis, Crohn's disease, celiac disease and tendonitis. FDA evaluated only ulcerative colitis, declining the other three because the nomination did not include sufficient information and FDA identified no clinical studies in those populations.", "note": "This is an EVIDENTIARY VACUUM, NOT A REGULATORY LOOPHOLE — the distinction is the opposite of how the market reads it. FDA did not decline to evaluate tendonitis because tendon use is somehow outside its remit; it declined because nobody submitted evidence and no clinical studies exist. That cuts against the recovery-market claims, not for them. Separately, and regardless of which uses were evaluated: BPC-157 is not on the 503A bulks list, so it may not lawfully be used in 503A compounding for ANY use. That follows from its absence from the list itself, not from the scope of FDA's evaluation.", "source": { "url": "https://www.fda.gov/media/193343/download", "title": "BPC-157-Related Bulk Drug Substances — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, July 23-24, 2026", "publisher": "FDA", "date": "2026-07-23", "quote": "BPC-157 was nominated for use in UC, Crohn's disease, Celiac disease, and tendonitis. However, FDA did not evaluate the proposed uses of Crohn's disease, Celiac disease, and tendonitis because the nomination did not include sufficient information for the Agency to evaluate whether the substance is appropriate for these uses in compounded drug products. In addition, FDA did not identify clinical studies using BPC-157 in these populations." }, "verifiedAt": "2026-07-16" }, { "finding": "FDA found a lack of evidence of effectiveness for BPC-157 in ulcerative colitis — the single use it agreed to evaluate — resting on one small trial reported only as a meeting abstract.", "note": "The trial is Ruenzi et al. 2005: 53 subjects with mild-to-moderate UC randomised 1:1 to a BPC-157 enema or placebo. Per FDA's summary of the abstract, the between-group difference in Disease Activity Index was 1.6 points with a 95% CI of -4.84 to 1.62 — an interval that crosses zero. This is the ONLY randomised controlled trial of BPC-157 in humans that FDA identified, it was never published in full, and it does not show a benefit.", "source": { "url": "https://www.fda.gov/media/193343/download", "title": "BPC-157-Related Bulk Drug Substances — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, July 23-24, 2026", "publisher": "FDA", "date": "2026-07-23", "quote": "There is a lack of evidence to support the effectiveness of BPC-157 (free base) and BPC-157 acetate as a treatment for UC. There has been a single, small trial evaluating BPC-157 in the treatment of UC, however, interpretation of the results is limited by the lack of details provided in the meeting abstract and the exploratory nature of the study." }, "verifiedAt": "2026-07-16" }, { "finding": "FDA identified no studies administering BPC-157 to humans by any of the routes it is actually sold for — oral, subcutaneous, nasal or transdermal.", "note": "This is the finding that matters most against the consumer market, and it is easy to miss. Human administration of BPC-157 is not zero — FDA counted five clinical studies, and the two it discusses in detail used a RECTAL ENEMA. Injection, capsules and nasal sprays are how BPC-157 is overwhelmingly sold. FDA found no human study using any of them. So the honest statement is not 'no human data' — it is that the human data that exists was generated by a route almost nobody buys, and cannot be carried across to the routes they do.", "source": { "url": "https://www.fda.gov/media/193343/download", "title": "BPC-157-Related Bulk Drug Substances — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, July 23-24, 2026", "publisher": "FDA", "date": "2026-07-23", "quote": "There is insufficient clinical safety information to characterize the safety profile of BPC-157 (free base) and BPC-157 acetate. We found no studies that administered BPC-157 to humans via the proposed oral, SC, nasal, or transdermal ROA." }, "verifiedAt": "2026-07-16" }, { "finding": "FDA considers both BPC-157 (free base) and BPC-157 acetate not well-characterized, and cannot rule out immunogenicity from impurities and peptide aggregates.", "note": "A characterization failure, not an evidence failure — a separate and independent ground for the proposal. FDA notes it has 'encountered multiple salts, and derivatives, including different active moieties, sold commercially under the same common name', and that neither nomination's certificate of analysis matched the substance nominated. Both nominators nominated by a code matching the free base and attached a CoA for the acetate. FDA's concern is explicit: patients 'may be dosed with a different bulk drug substance than the physician ordered'. Note this cuts against the common assumption that a CoA settles the question of what is in the vial.", "source": { "url": "https://www.fda.gov/media/193343/download", "title": "BPC-157-Related Bulk Drug Substances — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, July 23-24, 2026", "publisher": "FDA", "date": "2026-07-23", "quote": "Because there is lack of information regarding potential impurities that can be present in BPC-157 (free base) and the lack of information on the potential of peptide aggregation, we cannot rule out the potential for immunogenicity associated with these impurities and peptide-related aggregates." }, "verifiedAt": "2026-07-16" }, { "finding": "No approved drug product containing BPC-157 exists in any country, and there is no USP, European, Japanese or International Pharmacopeia monograph for it.", "note": "Not merely 'not FDA-approved'. FDA searched globalEDGE and found BPC-157 is not a component of an approved product ANYWHERE. There is no jurisdiction to point at, which forecloses the usual 'approved in Europe / available abroad' framing. FDA also records that New Zealand's Medicines Classification Committee proposed in May 2023 that BPC-157 be classified as a prescription medicine — a restriction, not an approval.", "source": { "url": "https://www.fda.gov/media/193343/download", "title": "BPC-157-Related Bulk Drug Substances — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, July 23-24, 2026", "publisher": "FDA", "date": "2026-07-23", "quote": "There is no approved product containing BPC-157-related BDSs in any country at this time, nor is BPC-157 (free base) or BPC-157 acetate found in the European, Japanese, or the International Pharmacopeias." }, "verifiedAt": "2026-07-16" }, { "finding": "FDA's outsourcing facility product reporting data from January 2017 to June 2025 records no compounded drug products containing BPC-157 (free base) or BPC-157 acetate.", "note": "Read this precisely. It is a report of ZERO from registered 503B outsourcing facilities over eight and a half years — it is not evidence that nobody is compounding BPC-157. FDA's own search found compounding-pharmacy and med-spa websites marketing it, and FAERS reports naming the compounding pharmacies by name. What the zero establishes is that BPC-157 has no documented history of legitimate compounding for FDA to weigh, which is one of the criteria the evaluation turns on. FDA's conclusion: available data 'is too limited for FDA to understand the historical use'.", "source": { "url": "https://www.fda.gov/media/193343/download", "title": "BPC-157-Related Bulk Drug Substances — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, July 23-24, 2026", "publisher": "FDA", "date": "2026-07-23", "quote": "According to the FDA's outsourcing facility product reporting data from January 2017 to June 2025, there were no reported compounded drug products containing BPC-157 (free base) or BPC-157 acetate." }, "verifiedAt": "2026-07-16" }, { "finding": "FDA's briefing document records that BPC-157 is on the World Anti-Doping Agency's prohibited list, in the S0 non-approved substances section.", "note": "S0 is the category for substances with no current approval by any governmental regulatory health authority for human therapeutic use. Prohibited at all times, in and out of competition. Directly relevant because the recovery and athletic market is where BPC-157 is chiefly sold.", "source": { "url": "https://www.fda.gov/media/193343/download", "title": "BPC-157-Related Bulk Drug Substances — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, July 23-24, 2026", "publisher": "FDA", "date": "2026-07-23", "quote": "BPC-157 is listed on the World Anti-Doping Agency's prohibited list under the non-approved substances (S0) section." }, "verifiedAt": "2026-07-16" } ], "safetySignals": [ { "signal": "Three FAERS reports, all associated with injectable BPC-157: injection-site redness and swelling, an emergency-department visit for shortness of breath, and reproducible hyperpigmentation on rechallenge.", "note": "Three, not two — count them against the document. FDA ID 194222121: a 55-year-old woman using BPC-157 injection compounded by Promise Pharmacy reported 9 days of injection-site redness and swelling. FDA ID 23130696: a 28-year-old man using BPC-157 acetate compounded by Revive Rx Pharmacy developed shortness of breath resulting in an emergency room visit. FDA ID 26053573: a 40-year-old woman using a BPC-157/TB500 product from Cellular Peptide LLC labelled 'research purposes only' developed diffuse hyperpigmentation and gingival darkening, with identical reproducible reactions on rechallenge. FDA's limitation on each report is DIFFERENT, and flattening them into one is how this gets misread: concomitant thymosin in the first; in the second, 'No further information was provided (i.e. duration of use, concomitant medications, or temporal relationship to product)' — information absent, not another drug present; and in the third FDA went the other way, writing that the AEs 'were likely due to the drug product considering that the AEs occurred upon rechallenge', limited only because the product contained two peptides. FDA did examine the recovery market under safety — the 'wolverine compound' marketing appears in the briefing document. The claim that FDA simply never looked at athletic use is wrong.", "source": { "url": "https://www.fda.gov/media/193343/download", "title": "BPC-157-Related Bulk Drug Substances — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, July 23-24, 2026", "publisher": "FDA", "date": "2026-07-23", "quote": "The Office of Surveillance and Epidemiology conducted a search of the FAERS database for reports of adverse events (AEs) for BPC-157 through December 4, 2025. The search retrieved three reports. All reports were associated with injectable BPC-157." }, "verifiedAt": "2026-07-16" }, { "signal": "In 28-day repeat-dose toxicity studies in rats and dogs, FDA characterised the reported findings as clinically relevant safety signals: altered clotting properties (aPTT shortening in rats, aPTT prolongation in dogs) and liver-associated signals.", "note": "Worth stating plainly because BPC-157 is marketed as having a clean animal safety record. It is FDA, not a critic, calling these signals clinically relevant, and they are in the SAME paper (Xu et al. 2020) the market cites for the finding that BPC-157 is not a mutagen. The intramuscular route used here is not one of the nominated routes, and FDA notes that because bioavailability by the nominated routes is unknown, these animal exposures cannot be used to estimate safety margins for them. FDA also identified no carcinogenicity studies at all, and no studies covering a complete reproductive cycle.", "source": { "url": "https://www.fda.gov/media/193343/download", "title": "BPC-157-Related Bulk Drug Substances — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, July 23-24, 2026", "publisher": "FDA", "date": "2026-07-23", "quote": "Findings from repeat-dose toxicity studies suggested that 28-day treatment of rats and dogs with BPC-157 (free base) via the IM ROA appeared to be associated with clinically relevant safety signals, including: (i) aPTT shortening and aPTT prolongation (suggestive of altered clotting properties) in rats and dogs, respectively, and (ii) liver-associated signals (increased serum ALT, glucose, and TG levels)." }, "verifiedAt": "2026-07-16" }, { "signal": "FDA identified no study that formally investigated the immunogenicity of any BPC-157 product, and states BPC-157 may pose a significant immunogenicity risk when injected or given nasally.", "note": "The burden runs the other way from how the market reads it. FDA's closing line on this is 'The nomination did not include, and FDA is not aware of, information about BPC-157 to suggest that this substance does not present these risks.' Absence of reported harm is not the same as evidence of safety, and here there is no immunogenicity study to be absent from.", "source": { "url": "https://www.fda.gov/media/193343/download", "title": "BPC-157-Related Bulk Drug Substances — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, July 23-24, 2026", "publisher": "FDA", "date": "2026-07-23", "quote": "The nominators did not provide, and we did not identify any studies that formally investigated the immunogenicity of BPC-157 products. As a peptide with 15 amino acids that is administered through a parenteral or nasal ROA, BPC-157 may pose a significant risk for immunogenicity, potentially amplified by aggregation as well as potential peptide-related impurities …" }, "verifiedAt": "2026-07-16" } ], "faqs": [ { "question": "Is BPC-157 legal in 2026?", "answer": "No — BPC-157 may not lawfully be used in pharmacy compounding under section 503A of the Federal Food, Drug, and Cosmetic Act, because it is absent from FDA's 503A bulk drug substances list, which was last updated on 14 May 2026. BPC-157 is also not an approved drug product in any country. Being absent from the list is not a neutral status: a bulk drug substance that is neither the subject of a USP monograph nor a component of an approved drug must appear on that list to be used in 503A compounding, and BPC-157 does not appear on it in any category.", "source": { "url": "https://www.fda.gov/media/94155/download", "title": "Bulk Drug Substances Nominated for Use in Compounding Under Section 503A of the Federal Food, Drug, and Cosmetic Act", "publisher": "FDA", "date": "2026-05-14" }, "verifiedAt": "2026-07-16" }, { "question": "Did BPC-157 become legal again when FDA removed it from Category 2?", "answer": "No. BPC-157 left FDA's Category 2 because the two nominators — Wells Pharmacy Network and LDT Health Solutions — withdrew their nominations, not because FDA resolved anything in BPC-157's favour. FDA's own briefing document states: 'The nominations were withdrawn and FDA is evaluating the substances at its discretion.' The status moved sideways, not toward legality: BPC-157 did not enter Category 1, it is not on the 503A bulks list, and it remains unusable in 503A compounding. FDA continued the evaluation on its own initiative and its staff have since proposed not adding BPC-157 to the list at all.", "source": { "url": "https://www.fda.gov/media/193343/download", "title": "BPC-157-Related Bulk Drug Substances — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, July 23-24, 2026", "publisher": "FDA", "date": "2026-07-23", "quote": "The nominations were withdrawn and FDA is evaluating the substances at its discretion." }, "verifiedAt": "2026-07-16" }, { "question": "Is there any human evidence that BPC-157 works?", "answer": "No — FDA identified one randomised controlled trial of BPC-157 in humans, reported only as a 2005 meeting abstract, and it did not demonstrate a benefit. In that trial 53 subjects with mild-to-moderate ulcerative colitis were randomised 1:1 to a BPC-157 enema or placebo; per FDA's summary, the between-group difference in Disease Activity Index was 1.6 points with a 95% confidence interval of -4.84 to 1.62, an interval that crosses zero. FDA's conclusion was that 'There is a lack of evidence to support the effectiveness of BPC-157 (free base) and BPC-157 acetate as a treatment for UC.' The claims BPC-157 is chiefly sold on — tendon, ligament and gut healing — rest on rodent studies; FDA identified no clinical studies of BPC-157 in tendonitis, Crohn's disease or celiac disease at all.", "source": { "url": "https://www.fda.gov/media/193343/download", "title": "BPC-157-Related Bulk Drug Substances — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, July 23-24, 2026", "publisher": "FDA", "date": "2026-07-23", "quote": "There is a lack of evidence to support the effectiveness of BPC-157 (free base) and BPC-157 acetate as a treatment for UC." }, "verifiedAt": "2026-07-16" }, { "question": "Can I get BPC-157 from a compounding pharmacy?", "answer": "Not lawfully. BPC-157 is absent from FDA's 503A bulk drug substances list, which is what a pharmacy would need to compound it under section 503A, and FDA's outsourcing facility product reporting data from January 2017 to June 2025 records no compounded drug products containing BPC-157 (free base) or BPC-157 acetate from any registered 503B outsourcing facility. That said, FDA reports that 'A Google search for BPC-157 generally identified websites of compounding pharmacies as well as several med spas and clinics in the United States that mentioned BPC-157 for a variety of uses', and all three BPC-157 adverse event reports in FDA's FAERS database name a compounding pharmacy or a seller. Being obtainable and being lawful are not the same question.", "source": { "url": "https://www.fda.gov/media/193343/download", "title": "BPC-157-Related Bulk Drug Substances — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, July 23-24, 2026", "publisher": "FDA", "date": "2026-07-23", "quote": "According to the FDA's outsourcing facility product reporting data from January 2017 to June 2025, there were no reported compounded drug products containing BPC-157 (free base) or BPC-157 acetate. […] A Google search for BPC-157 generally identified websites of compounding pharmacies as well as several med spas and clinics in the United States that mentioned BPC-157 for a variety of uses …" }, "verifiedAt": "2026-07-16" }, { "question": "Is BPC-157 safe?", "answer": "Unknown — FDA states that 'There is insufficient clinical safety information to characterize the safety profile of BPC-157 (free base) and BPC-157 acetate.' FDA found no study that administered BPC-157 to humans by the oral, subcutaneous, nasal or transdermal routes it is sold for, no study that formally investigated its immunogenicity, and no carcinogenicity studies. Three adverse event reports appear in FDA's FAERS database: an injection-site reaction, shortness of breath resulting in an emergency room visit, and diffuse hyperpigmentation with gingival darkening that recurred identically on rechallenge. FDA's interpretation of each report is limited, but for a different reason each time — by concomitant thymosin in the first, by missing information in the second, and in the third, where FDA judged the reactions 'likely due to the drug product considering that the AEs occurred upon rechallenge', by the product containing two peptides. FDA states it 'cannot make definitive conclusions regarding the safety of BPC-157 based on FAERS data alone'. An unstudied compound is not a compound shown to be safe.", "source": { "url": "https://www.fda.gov/media/193343/download", "title": "BPC-157-Related Bulk Drug Substances — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, July 23-24, 2026", "publisher": "FDA", "date": "2026-07-23", "quote": "There is insufficient clinical safety information to characterize the safety profile of BPC-157 (free base) and BPC-157 acetate." }, "verifiedAt": "2026-07-16" }, { "question": "What did FDA propose at the July 2026 PCAC meeting about BPC-157?", "answer": "FDA staff proposed not adding BPC-157 to the 503A bulks list, in the briefing document for the Pharmacy Compounding Advisory Committee meeting of 23-24 July 2026: 'Accordingly, we propose not adding BPC-157 (free base) or BPC-157 acetate to the 503A Bulks List.' FDA gave four grounds: the substances are not well characterized physicochemically; there is a lack of information on their safety profile and immunogenicity risks; there is insufficient evidence to conclude they are effective for ulcerative colitis; and FDA-approved drug products already exist for ulcerative colitis. This is a staff proposal, not a final determination — the document states FDA 'will not issue a final determination on the issues at hand until input from the advisory committee process has been considered and all reviews have been finalized.' It does not change BPC-157's current status, which is that it is not on the list.", "source": { "url": "https://www.fda.gov/media/193343/download", "title": "BPC-157-Related Bulk Drug Substances — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, July 23-24, 2026", "publisher": "FDA", "date": "2026-07-23", "quote": "Accordingly, we propose not adding BPC-157 (free base) or BPC-157 acetate to the 503A Bulks List." }, "verifiedAt": "2026-07-16" } ] }, { "slug": "cagrilintide", "name": "Cagrilintide", "aliases": [ "CagriSema", "cagrilintide-semaglutide" ], "url": "https://peptides101.com/compounds/cagrilintide", "moleculeNote": "A long-acting amylin analogue — a different receptor system from the GLP-1 agonists it is sold alongside. The disambiguation that matters on this record is PRODUCT, not sequence. 'CagriSema' and 'cagrilintide-semaglutide' are listed above as aliases because that is what people search, NOT because they name the same substance: CagriSema is a fixed-dose combination of cagrilintide and semaglutide, so every CagriSema result is a result for two molecules given together, one of which is the most heavily evidenced peptide on this site. A number attributed to CagriSema is not a number attributed to cagrilintide. The trials cited below are read with that split kept intact.", "quickAnswer": "Cagrilintide is not an FDA-approved drug. FDA has stated that 'Retatrutide and cagrilintide cannot be used in compounding under federal law' and that these 'are not components of FDA-approved drugs and have not been found safe and effective for any condition.' Cagrilintide is a long-acting amylin analogue in active Phase 3 development by Novo Nordisk, which submitted a New Drug Application to FDA on 18 December 2025 for CagriSema — a fixed-dose combination of cagrilintide and semaglutide, not cagrilintide on its own — and which states that 'CagriSema is not approved in the US or EU.' The published trial results belong to that combination: in REDEFINE 1 (N Engl J Med 2025), 302 of 3417 randomised participants were assigned to receive cagrilintide alone, but the trial's coprimary endpoints compared cagrilintide-semaglutide with placebo. The Phase 3 trial designed to test cagrilintide by itself, NCT07220642, has a primary completion date of 11 May 2027 and no posted results.", "fdaStatus": { "value": "investigational", "note": "In active clinical development with an identifiable sponsor and registered trials. Not approved. Being in trials is not evidence that it works, and being in someone else's combination trial is not evidence about the single molecule. WHAT WAS CHECKED, because the negative half is the harder half. Drugs@FDA was queried through the openFDA API on 2026-08-02 on THREE fields, not one — openfda.generic_name, products.active_ingredients.name and openfda.brand_name (CAGRISEMA). All three returned NOT_FOUND. Querying a single field is how a false 'not in Drugs@FDA' claim gets made in this library, so the check is recorded rather than asserted. FDA states independently, in its own words, that cagrilintide is not a component of an FDA-approved drug — recorded verbatim under FDA findings. SCOPE OF THE PENDING APPLICATION: the NDA Novo Nordisk submitted on 2025-12-18 is for CagriSema, the fixed-dose combination, not for cagrilintide as a single-agent product. Cagrilintide on its own is the subject of a separate Phase 3 trial that has not read out (NCT07220642, primary completion 2027-05-11). So even a CagriSema approval would not make cagrilintide an approved single-agent medicine. 'Investigational' is assigned on the active-development test the vocabulary sets: an identifiable sponsor (Novo Nordisk A/S) with registered, currently active Phase 3 trials — NCT07220642 and NCT05567796 both ACTIVE_NOT_RECRUITING, NCT07253285 and NCT07564414 both RECRUITING when ClinicalTrials.gov was queried on 2026-08-02. This is not a terminated programme being sold as a live one.", "source": { "url": "https://www.novonordisk.com/content/nncorp/global/en/news-and-media/news-and-ir-materials/news-details.html?id=916470", "title": "Novo Nordisk files for FDA approval of CagriSema, the first once-weekly combination of GLP-1 and amylin analogues for weight management", "publisher": "Novo Nordisk", "date": "2025-12-18", "quote": "Today, Novo Nordisk announced the submission of a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for once-weekly CagriSema … CagriSema is a fixed-dose combination of a long-acting amylin analogue, cagrilintide …, and the GLP-1 receptor agonist, semaglutide …. CagriSema is not approved in the US or EU." }, "verifiedAt": "2026-08-02" }, "compoundingStatus": null, "evidence": { "tier": "promising-but-unproven", "humanAdministrationChecked": true, "note": "ADMINISTRATION CHECK RUN, NOT ASSUMED. The REDEFINE 1 report (N Engl J Med 2025;393:635-647, PMID 40544433) and the registration (NCT05567796) were both opened on 2026-08-02. Cagrilintide was ADMINISTERED: intervention type DRUG, given subcutaneously, with a dedicated monotherapy arm of 302 randomised participants. It was not measured as an endogenous biomarker, which is the trap that reduces MOTS-c and TB-500 from an apparent five human trials to an actual zero. Registration hygiene also checked — lead sponsor Novo Nordisk A/S, Phase 3, and the trial is reported in a peer-reviewed journal, so this is not a cloned or shell registration. WHY NOT A HIGHER TIER. The tier vocabulary reserves 'proven-in-humans' for efficacy established by adequate, well-controlled trials, and for cagrilintide AS A PRODUCT that does not exist yet. Read what REDEFINE 1 was designed to answer: its coprimary endpoints compare cagrilintide-semaglutide with placebo. The cagrilintide-alone arm is a reference arm, not the tested hypothesis, and the published abstract does not report a weight result for it — a genuine blank in the source cited here, recorded rather than filled. REDEFINE 2 (PMID 40544432) enrolled no cagrilintide-alone arm at all: 1206 patients randomised, cagrilintide-semaglutide versus placebo only. The single trial designed to test cagrilintide by itself, NCT07220642, has a primary completion date of 2027-05-11 and no posted results. SCOPE. Whatever this tier is worth, it attaches to the molecule Novo Nordisk administered under an IND in these trials. It does not travel to a vial sold under the same name, and FDA states cagrilintide is not a component of any FDA-approved drug, so no such vial comes from an approved supply.", "source": { "url": "https://pubmed.ncbi.nlm.nih.gov/40544433/", "title": "Coadministered Cagrilintide and Semaglutide in Adults with Overweight or Obesity (Garvey WT et al., REDEFINE 1 Study Group)", "publisher": "PubMed", "date": "2025-08-14", "quote": "The coprimary end points were the relative change in body weight and a reduction of 5% or more in body weight from baseline to week 68 with cagrilintide-semaglutide as compared with placebo. … A total of 3417 participants underwent randomization, with 2108 assigned to receive cagrilintide-semaglutide, 302 to receive semaglutide, 302 to receive cagrilintide, and 705 to receive placebo." }, "verifiedAt": "2026-08-02" }, "fdaApproval": null, "fdaFindings": [ { "finding": "FDA has stated that retatrutide and cagrilintide cannot be used in compounding under federal law, that they are not components of FDA-approved drugs, and that they have not been found safe and effective for any condition.", "note": "The only FDA-authored sentence on this record that names cagrilintide, and it does three separate jobs: it forecloses compounding, it establishes that cagrilintide is in no approved product, and it states that FDA has made no finding of safety or effectiveness for it in any condition. That third clause is the one to hold onto while reading the Phase 3 results below — a completed trial with a published result is not an agency finding, and FDA's position is unchanged by REDEFINE 1. READ THE SCOPE PRECISELY, because this page invites an overreach. Immediately beneath this sentence FDA lists parties it has warned — telehealth companies, API distributors, outsourcing facilities — and every one of those bullets names RETATRUTIDE, not cagrilintide. Do not carry the enforcement examples across to cagrilintide; the shared heading does not make them shared actions. What is shared is the legal conclusion in the quoted sentence.", "source": { "url": "https://www.fda.gov/drugs/drug-alerts-and-statements/fdas-concerns-unapproved-glp-1-drugs-used-weight-loss", "title": "FDA's Concerns with Unapproved GLP-1 Drugs Used for Weight Loss", "publisher": "FDA", "date": "2026-06-15", "quote": "Retatrutide and cagrilintide cannot be used in compounding under federal law. Additionally, these are not components of FDA-approved drugs and have not been found safe and effective for any condition." }, "verifiedAt": "2026-08-02" }, { "finding": "Cagrilintide appears in none of Categories 1, 2 or 3 of FDA's 503A bulk drug substances list updated 2026-05-14, and does not appear on FDA's companion page listing bulk drug substances nominated but withdrawn.", "note": "Verified by downloading the PDF with a browser user-agent and text-extracting it locally on 2026-08-02: 'cagrilintide' returns zero hits across all seven pages. The companion safety-risks page, which carries the table headed 'Bulk drug substances nominated but withdrawn', likewise returns zero hits. Recorded to close a misreading, not to assert a status — which is why this record carries no 503A badge at all. Cagrilintide's absence means something different from BPC-157's. BPC-157 was nominated and left Category 2 when its nominators withdrew; cagrilintide was never in the nomination system, so there is no category, no withdrawal and no proceeding to describe. Categorical silence is neither permission nor a safety finding, and it is not what makes cagrilintide non-compoundable — FDA's own statement above is.", "source": { "url": "https://www.fda.gov/media/94155/download", "title": "Bulk Drug Substances Nominated for Use in Compounding Under Section 503A of the Federal Food, Drug, and Cosmetic Act", "publisher": "FDA", "date": "2026-05-14" }, "verifiedAt": "2026-08-02" } ], "safetySignals": [ { "signal": "In the REDEFINE 1 Phase 3 trial, gastrointestinal adverse events were reported in 79.6% of the cagrilintide-semaglutide group and 39.9% of the placebo group; the investigators reported them as mainly transient and mild-to-moderate in severity.", "note": "Read the group label. This rate is for the COMBINATION arm, not for cagrilintide alone. REDEFINE 1 randomised a cagrilintide-alone arm of 302 participants, and the published abstract cited here does not report an adverse-event rate for it — so this record does not state one. That is a blank in the source, and filling it by assuming the combination figure describes the single agent would be exactly the attribution error this record exists to prevent, run in the direction of harm instead of benefit.", "source": { "url": "https://pubmed.ncbi.nlm.nih.gov/40544433/", "title": "Coadministered Cagrilintide and Semaglutide in Adults with Overweight or Obesity (Garvey WT et al., REDEFINE 1 Study Group)", "publisher": "PubMed", "date": "2025-08-14", "quote": "Gastrointestinal adverse events (affecting 79.6% in the cagrilintide-semaglutide group and 39.9% in the placebo group), including nausea, vomiting, diarrhea, constipation, or abdominal pain, were mainly transient and mild-to-moderate in severity." }, "verifiedAt": "2026-08-02" }, { "signal": "In the REDEFINE 2 Phase 3 trial in adults with type 2 diabetes, gastrointestinal adverse events were reported by 72.5% of patients in the cagrilintide-semaglutide group and 34.4% in the placebo group; the investigators reported most as transient and mild or moderate in severity.", "note": "A second, independent trial reporting the same shape of signal, in a different population (1206 patients with type 2 diabetes and obesity or overweight). REDEFINE 2 had no cagrilintide-alone arm — it randomised the combination against placebo only — so it says nothing at all about cagrilintide as a single agent, and is recorded here for the combination in which cagrilintide's human exposure has overwhelmingly occurred.", "source": { "url": "https://pubmed.ncbi.nlm.nih.gov/40544432/", "title": "Cagrilintide-Semaglutide in Adults with Overweight or Obesity and Type 2 Diabetes (Davies MJ et al., REDEFINE 2 Study Group)", "publisher": "PubMed", "date": "2025-08-14", "quote": "Gastrointestinal adverse events were reported by 72.5% of the patients in the cagrilintide-semaglutide group and 34.4% in the placebo group, most of which were transient and mild or moderate in severity." }, "verifiedAt": "2026-08-02" }, { "signal": "Novo Nordisk reported discontinuation rates due to adverse events of 5.9% for CagriSema versus 3.5% for placebo in REDEFINE 1, and 8.4% versus 3% in REDEFINE 2.", "note": "The figures are the sponsor's; so is the word 'low', which is a characterisation and not a finding, and it is left inside the quotation marks rather than repeated as this site's own assessment. What the numbers themselves show is a discontinuation rate roughly one and a half to nearly three times the placebo rate across the two trials. Again this is the combination, not cagrilintide alone.", "source": { "url": "https://www.novonordisk.com/content/nncorp/global/en/news-and-media/news-and-ir-materials/news-details.html?id=916470", "title": "Novo Nordisk files for FDA approval of CagriSema, the first once-weekly combination of GLP-1 and amylin analogues for weight management", "publisher": "Novo Nordisk", "date": "2025-12-18", "quote": "Overall, discontinuation rates due to adverse events were low, with 5.9% for CagriSema versus 3.5% for placebo in REDEFINE 1 and 8.4% with CagriSema versus 3% with placebo in REDEFINE 2." }, "verifiedAt": "2026-08-02" } ], "faqs": [ { "question": "Is cagrilintide FDA-approved in 2026?", "answer": "No. Cagrilintide is not an FDA-approved drug and is not an ingredient in one. FDA states that retatrutide and cagrilintide 'are not components of FDA-approved drugs and have not been found safe and effective for any condition.' Novo Nordisk submitted a New Drug Application to FDA on 18 December 2025 for CagriSema, a fixed-dose combination of cagrilintide and semaglutide, and states in its own announcement that 'CagriSema is not approved in the US or EU.' Two things follow that are easy to miss. First, an application under review is not an approval — a Drugs@FDA query through the openFDA API on 2 August 2026 returned no matching application for cagrilintide on generic name, active ingredient name or the brand name CagriSema. Second, the pending application is for the combination product, so even an approval of CagriSema would not make cagrilintide an approved single-agent medicine.", "source": { "url": "https://www.fda.gov/drugs/drug-alerts-and-statements/fdas-concerns-unapproved-glp-1-drugs-used-weight-loss", "title": "FDA's Concerns with Unapproved GLP-1 Drugs Used for Weight Loss", "publisher": "FDA", "date": "2026-06-15", "quote": "Retatrutide and cagrilintide cannot be used in compounding under federal law. Additionally, these are not components of FDA-approved drugs and have not been found safe and effective for any condition." }, "verifiedAt": "2026-08-02" }, { "question": "Can I get cagrilintide from a compounding pharmacy?", "answer": "Not lawfully. FDA states plainly that 'Retatrutide and cagrilintide cannot be used in compounding under federal law.' The mechanism is worth understanding rather than taking on faith: a bulk drug substance that is neither the subject of an applicable USP or NF monograph nor a component of an FDA-approved drug product must appear on FDA's 503A bulks list to be used in compounding under section 503A. FDA states cagrilintide is not a component of an FDA-approved drug, and cagrilintide returns zero hits in the 503A bulks list document updated 14 May 2026 — verified on 2 August 2026 by downloading the PDF and extracting its text. Note what that absence is not: cagrilintide is not in Category 1, 2 or 3, and it does not appear on FDA's list of substances nominated but withdrawn either. It was never in the nomination system at all, which is why this record carries no 503A category. The absence is not permission and it is not a safety finding.", "source": { "url": "https://www.fda.gov/drugs/drug-alerts-and-statements/fdas-concerns-unapproved-glp-1-drugs-used-weight-loss", "title": "FDA's Concerns with Unapproved GLP-1 Drugs Used for Weight Loss", "publisher": "FDA", "date": "2026-06-15", "quote": "Retatrutide and cagrilintide cannot be used in compounding under federal law." }, "verifiedAt": "2026-08-02" }, { "question": "How much weight did people lose on cagrilintide in the REDEFINE 1 trial?", "answer": "The published REDEFINE 1 abstract does not report a weight result for the cagrilintide-alone group, and this is the single most misquoted point about this compound. What the trial reported is the combination: of 3417 participants randomised, 2108 were assigned to receive cagrilintide-semaglutide, 302 to semaglutide alone, 302 to cagrilintide alone and 705 to placebo, and the investigators reported an estimated mean change in body weight from baseline to week 68 of -20.4% with cagrilintide-semaglutide compared with -3.0% with placebo (estimated difference -17.3 percentage points, 95% confidence interval -18.1 to -16.6). Those coprimary endpoints compared the combination with placebo. Semaglutide is separately an FDA-approved active ingredient with its own large trial record, so attributing the combination's result to cagrilintide credits one molecule with a result produced by two.", "source": { "url": "https://pubmed.ncbi.nlm.nih.gov/40544433/", "title": "Coadministered Cagrilintide and Semaglutide in Adults with Overweight or Obesity (Garvey WT et al., REDEFINE 1 Study Group)", "publisher": "PubMed", "date": "2025-08-14", "quote": "A total of 3417 participants underwent randomization, with 2108 assigned to receive cagrilintide-semaglutide, 302 to receive semaglutide, 302 to receive cagrilintide, and 705 to receive placebo. The estimated mean percent change in body weight from baseline to week 68 was -20.4% with cagrilintide-semaglutide as compared with -3.0% with placebo (estimated difference, -17.3 percentage points; 95% confidence interval, -18.1 to -16.6; P<0.001)." }, "verifiedAt": "2026-08-02" }, { "question": "Did CagriSema beat tirzepatide?", "answer": "No. Novo Nordisk announced on 23 February 2026 that REDEFINE 4, an open-label head-to-head Phase 3 trial in 809 randomised people with obesity and one or more comorbidities, 'did not achieve its primary endpoint of demonstrating non-inferiority on weight loss for CagriSema compared to tirzepatide after 84 weeks.' The sponsor reported weight loss of 23.0% with CagriSema versus 25.5% with tirzepatide after 84 weeks when evaluating the effects of treatment if all people adhered to treatment, and 20.2% versus 23.6% under the treatment-regimen estimand. Read the design limits with the result: the trial was open-label, meaning investigators and participants knew which drug was given, and it tested the CagriSema combination, not cagrilintide on its own. This is a sponsor announcement of headline results, reported by the sponsor against its own product.", "source": { "url": "https://www.novonordisk.com/content/nncorp/global/en/news-and-media/news-and-ir-materials/news-details.html?id=916501", "title": "Novo Nordisk A/S: CagriSema demonstrated 23% weight loss in an open-label head-to-head REDEFINE 4 trial in people with obesity, the primary endpoint was not achieved", "publisher": "Novo Nordisk", "date": "2026-02-23", "quote": "The trial did not achieve its primary endpoint of demonstrating non-inferiority on weight loss for CagriSema compared to tirzepatide after 84 weeks." }, "verifiedAt": "2026-08-02" }, { "question": "Is cagrilintide being studied on its own, without semaglutide?", "answer": "Yes, and it has not reported. Novo Nordisk A/S is the lead sponsor of NCT07220642, a Phase 3 trial titled 'Efficacy and Safety of Cagrilintide for Weight Management in Participants With Overweight or Obesity', which randomises participants to cagrilintide or to matching placebo administered subcutaneously, with relative change in body weight as its primary outcome measure. Checked on 2 August 2026: status ACTIVE_NOT_RECRUITING, estimated enrolment 300, primary completion date 11 May 2027, and no results posted. So the trial that would establish what cagrilintide does as a standalone product is running and unread. Until it reports, every published Phase 3 efficacy result for cagrilintide comes from a trial of the combination with semaglutide.", "source": { "url": "https://clinicaltrials.gov/study/NCT07220642", "title": "NCT07220642 — Efficacy and Safety of Cagrilintide for Weight Management in Participants With Overweight or Obesity", "publisher": "ClinicalTrials.gov", "date": "2026-06-26" }, "verifiedAt": "2026-08-02" }, { "question": "When will FDA decide on CagriSema?", "answer": "Novo Nordisk stated on 23 February 2026 that 'CagriSema for weight management was submitted to the US FDA in December 2025 based on the REDEFINE 1 and REDEFINE 2 pivotal trials, and an FDA decision is anticipated by late 2026.' That is the sponsor's expectation, not an FDA commitment, and FDA has published no approval: a Drugs@FDA query through the openFDA API on 2 August 2026 returned no application matching cagrilintide by generic name, by active ingredient name, or by the brand name CagriSema. An anticipated decision date is not an outcome — FDA can approve, refuse, or issue a complete response letter — and a pending application confers no legal status on cagrilintide in the meantime.", "source": { "url": "https://www.novonordisk.com/content/nncorp/global/en/news-and-media/news-and-ir-materials/news-details.html?id=916501", "title": "Novo Nordisk A/S: CagriSema demonstrated 23% weight loss in an open-label head-to-head REDEFINE 4 trial in people with obesity, the primary endpoint was not achieved", "publisher": "Novo Nordisk", "date": "2026-02-23", "quote": "CagriSema for weight management was submitted to the US FDA in December 2025 based on the REDEFINE 1 and REDEFINE 2 pivotal trials, and an FDA decision is anticipated by late 2026." }, "verifiedAt": "2026-08-02" }, { "question": "Is cagrilintide sold as a research peptide the same thing Novo Nordisk is testing?", "answer": "Nothing verifies that it is. FDA states that cagrilintide is not a component of an FDA-approved drug, which means no vial of it originates from an approved supply chain, and that it 'ha[s] not been found safe and effective for any condition.' The trial results on this page were generated with material manufactured and administered by Novo Nordisk under its own investigational programme; they describe that material and nothing else. One point of precision, because the FDA page invites an overreach: the enforcement examples listed immediately below FDA's cagrilintide sentence — warnings to telehealth companies, to active pharmaceutical ingredient distributors, and to outsourcing facilities — all name retatrutide, not cagrilintide. This record does not carry them across. What FDA has stated about cagrilintide is the legal conclusion quoted here.", "source": { "url": "https://www.fda.gov/drugs/drug-alerts-and-statements/fdas-concerns-unapproved-glp-1-drugs-used-weight-loss", "title": "FDA's Concerns with Unapproved GLP-1 Drugs Used for Weight Loss", "publisher": "FDA", "date": "2026-06-15", "quote": "Retatrutide and cagrilintide cannot be used in compounding under federal law. Additionally, these are not components of FDA-approved drugs and have not been found safe and effective for any condition." }, "verifiedAt": "2026-08-02" } ] }, { "slug": "cjc-1295", "name": "CJC-1295", "aliases": [ "CJC 1295", "CJC-1295 with DAC" ], "url": "https://peptides101.com/compounds/cjc-1295", "moleculeNote": "CJC-1295 as characterised in the literature is a tetrasubstituted form of human growth-hormone-releasing factor hGRF(1-29) carrying an added C-terminal lysine bearing an N-epsilon-3-maleimidopropionamide group, which bioconjugates in vivo to the free thiol on Cys34 of serum albumin — that albumin conjugation is the entire point of the molecule (Endocrinology 2005, PMID 15817669, in which the researchers reported CJC-1295 present in rat plasma beyond 72 h and an immunoreactive species on the serum-albumin band). The multi-day figure in humans is separate and comes from the 2006 healthy-adult trial, where the investigators estimated a half-life of 5.8-8.1 d (PMID 16352683); the 2005 paper is rat pharmacokinetics and does not establish it. What is sold under the name is not reliably that molecule. A preparation of unknown origin, submitted for analysis at the request of Norwegian police and customs authorities and analysed by LC-HRMS/MS, was reported to contain a 29-amino-acid peptide with a C-terminal amide function, which the authors state is 'consistent with a peptide currently marketed under the name CJC-1295' (Drug Test Anal 2010, PMID 21204297) — a 29-residue amidated peptide does not carry the added C-terminal maleimido-lysine. We record the juxtaposition, not an identification: neither paper adjudicates the other. The market convention of calling the albumin-binding form 'with DAC' and the short-acting form 'without DAC' has no FDA or literature standing, and FDA's own listing says only 'CJC-1295' without qualifying which molecule it means.", "quickAnswer": "CJC-1295 has no approved FDA application for any indication and cannot lawfully be used in 503A compounding: it appears in none of the three categories of the FDA 503A bulks list, and FDA lists it under 'Bulk drug substances nominated but withdrawn' — the nominators withdrew the nomination, which left CJC-1295 off the list exactly as before rather than moving it toward legality. Researchers did administer CJC-1295 to healthy adults in 2006, subcutaneously and in ascending doses, and reported dose-dependent rises in growth hormone and IGF-I (PMID 16352683), but every endpoint those trials measured was a hormone concentration, and the only registered trial designed to evaluate efficacy — ConjuChem's Phase 2 in HIV-associated visceral obesity — was terminated without posting results, so no efficacy trial of CJC-1295 has ever reported an outcome.", "fdaStatus": { "value": "not-approved", "note": "Not an FDA-approved drug for any indication, and not in active development toward approval. That says nothing about whether it is sold — it is.", "source": { "url": "https://www.fda.gov/drugs/human-drug-compounding/certain-bulk-drug-substances-use-compounding-may-present-significant-safety-risks", "title": "Certain Bulk Drug Substances for Use in Compounding that May Present Significant Safety Risks", "publisher": "FDA", "date": "2026-04-22", "quote": "This list of bulk drug substances previously in category 2 of the interim policies were withdrawn by the nominators." }, "verifiedAt": "2026-07-16" }, "compoundingStatus": { "value": "withdrawn-from-nomination", "note": "The withdrawal is established by THIS document, not by the bulks list. FDA's category-2 page carries CJC-1295 in the table under the heading 'Bulk drug substances nominated but withdrawn', which the page defines with the quoted sentence. That is what supports the value. Separately, CJC-1295 is absent from Categories 1, 2 and 3 of the 503A bulks list updated 2026-05-14 — verified by fetching and text-extracting that document directly; the string 'CJC' does not appear in it at all — but absence alone would establish only absence, and could not distinguish withdrawn from never-nominated. It is therefore NOT category-2, and this is not a legalisation event: CJC-1295 did not enter Category 1, is not on the 503A bulks list, and remains non-compoundable. Status moved sideways.", "source": { "url": "https://www.fda.gov/drugs/human-drug-compounding/certain-bulk-drug-substances-use-compounding-may-present-significant-safety-risks", "title": "Certain Bulk Drug Substances for Use in Compounding that May Present Significant Safety Risks", "publisher": "FDA", "date": "2026-04-22", "quote": "This list of bulk drug substances previously in category 2 of the interim policies were withdrawn by the nominators." }, "verifiedAt": "2026-07-16" }, "evidence": { "tier": "promising-but-unproven", "humanAdministrationChecked": true, "note": "ADMINISTRATION CHECK RUN, AND IT PASSES — which is the opposite of the MOTS-c and TB-500 outcome, and the reason this record is not animal-or-in-vitro-only. Both human papers were opened and read. In the 2006 trial (PMID 16352683, healthy adults aged 21-61, two randomised placebo-controlled double-blind ascending-dose trials of 28 and 49 days), researchers state CJC-1295 was administered subcutaneously and report dose-dependent increases in mean plasma GH and IGF-I. In a second 2006 study (PMID 17018654, healthy men aged 20-40), researchers report increased trough and mean GH secretion with preserved pulsatility after a single injection. The drug was given to people; it was not measured as an endogenous biomarker.\n\nWHY IT IS STILL UNPROVEN. Every endpoint in both papers is a hormone concentration — the 2006 trial's stated main outcome measures are 'peak concentrations and area under the curve of GH and IGF-I'. Neither study measured a clinical outcome. Raising IGF-I is a pharmacodynamic effect, not a demonstration of benefit, and the authors' own conclusion claims only that the data 'support the potential utility of CJC-1295 as a therapeutic agent'. The one trial designed to evaluate efficacy — NCT00267527, ConjuChem's randomised double-blind placebo-controlled Phase 2 in HIV-associated visceral obesity, 12 weeks, registered enrolment 120 — has overall status TERMINATED on ClinicalTrials.gov, verified against the registry API on 2026-07-16. The registry does not state whether that 120 is anticipated or actual, and for a terminated trial those are very different numbers, so it is reported here as the registered figure and nothing more. Its record carries no results and no outcome measures at all, its last update was posted 2006-10-16, and the registry record carries no why-stopped information, so the reason it stopped is not publicly known and we will not speculate. No efficacy trial of CJC-1295 has ever reported a result. Zero trials of it are indexed for any marketed use — body composition, recovery, sleep, anti-aging.\n\nREGISTRY HYGIENE. The CJC-1295 registry search returns exactly one study, sponsored by the developer in 2005. None of the 2026 single-sponsor 'Hudson Biotech' registrations contaminating this vertical touch this compound.", "source": { "url": "https://pubmed.ncbi.nlm.nih.gov/16352683/", "title": "Prolonged stimulation of growth hormone (GH) and insulin-like growth factor I secretion by CJC-1295, a long-acting analog of GH-releasing hormone, in healthy adults", "publisher": "PubMed", "date": "2006-03-01", "quote": "CJC-1295 or placebo was administered sc in one of four ascending single doses in the first study and in two or three weekly or biweekly doses in the second study." }, "verifiedAt": "2026-07-16" }, "fdaApproval": null, "fdaFindings": [ { "finding": "CJC-1295 appears in none of the three categories of the 503A bulks list updated 2026-05-14. It may not lawfully be used in 503A compounding for any use.", "note": "Recorded as its own finding because absence from a list establishes only absence. It carries the legal consequence — a substance not on the list is not available for 503A compounding, which follows from the absence itself — but it does NOT establish WHY CJC-1295 is absent. The withdrawal is established by the category-2 page below, not here.", "source": { "url": "https://www.fda.gov/media/94155/download", "title": "Bulk Drug Substances Nominated for Use in Compounding Under Section 503A of the Federal Food, Drug, and Cosmetic Act", "publisher": "FDA", "date": "2026-05-14" }, "verifiedAt": "2026-07-16" }, { "finding": "FDA lists CJC-1295 under 'Bulk drug substances nominated but withdrawn' — substances previously in category 2 of the interim policies whose nominations the nominators withdrew — and continues to publish the potential significant safety risks it identified for it.", "note": "The withdrawal removed the nomination, not the findings. FDA kept the safety text published on the same page after the substance left category 2, which is the fact that 'it's off the Category 2 list now' coverage omits.", "source": { "url": "https://www.fda.gov/drugs/human-drug-compounding/certain-bulk-drug-substances-use-compounding-may-present-significant-safety-risks", "title": "Certain Bulk Drug Substances for Use in Compounding that May Present Significant Safety Risks", "publisher": "FDA", "date": "2026-04-22", "quote": "This list of bulk drug substances previously in category 2 of the interim policies were withdrawn by the nominators." }, "verifiedAt": "2026-07-16" }, { "finding": "FDA has identified serious adverse events associated with CJC-1295 including increased heart rate and systemic vasodilatory reaction, and states that available clinical data are limited.", "note": "This finding sits in direct tension with the published trial, and readers should see both. The 2006 healthy-adult trial reports 'No serious adverse reactions were reported' (PMID 16352683). FDA, reviewing the nomination, says it identified serious adverse events. We cannot reconcile these from public documents: FDA's page does not cite the source, dates, route, number of cases, or molecule for the events it describes, and does not state whether it is drawing on trial data, FAERS, or post-marketing reports. Recording only the trial line would understate the risk; recording only FDA's line would imply a case series that we have not seen. Both are recorded verbatim and the gap is left open.", "source": { "url": "https://www.fda.gov/drugs/human-drug-compounding/certain-bulk-drug-substances-use-compounding-may-present-significant-safety-risks", "title": "Certain Bulk Drug Substances for Use in Compounding that May Present Significant Safety Risks", "publisher": "FDA", "date": "2026-04-22", "quote": "FDA has identified serious adverse events associated with CJC-1295 including increased heart rate and systemic vasodilatory reaction. Available clinical data are limited." }, "verifiedAt": "2026-07-16" }, { "finding": "FDA states that compounded drugs containing CJC-1295 may pose risk for immunogenicity for certain routes of administration and may have complexities with regard to peptide-related impurities and API characterization.", "note": "Quoted as printed, including the 'with regard to for' typo in FDA's own text. This is a finding about the SUBSTANCE AS COMPOUNDED — identity, purity and characterisation of the material in the vial — not about the pharmacology. It is the concern that the unknown-preparation analysis (PMID 21204297) makes concrete.", "source": { "url": "https://www.fda.gov/drugs/human-drug-compounding/certain-bulk-drug-substances-use-compounding-may-present-significant-safety-risks", "title": "Certain Bulk Drug Substances for Use in Compounding that May Present Significant Safety Risks", "publisher": "FDA", "date": "2026-04-22", "quote": "Compounded drugs containing CJC-1295 may pose risk for immunogenicity for certain routes of administration and may have complexities with regard to for peptide-related impurities and API characterization." }, "verifiedAt": "2026-07-16" }, { "finding": "Drugs@FDA, FDA's database of approved drug products, returns no matches for CJC-1295. There is no approved application for CJC-1295 for any indication or route.", "note": "The quote is the API's verbatim response body, not prose about it — which is the only honest way to cite an absence. Queried on generic name, active-ingredient name and brand name; all three return the same. The claim is deliberately narrow: it establishes that no approval EXISTS, not that FDA ever reviewed and refused one. Those are different facts and only the first is in evidence. CJC-1295 never reached an application — the developer's only clinical-endpoint trial was terminated in 2006 (NCT00267527) and development stopped there.", "source": { "url": "https://api.fda.gov/drug/drugsfda.json?search=openfda.generic_name:\"cjc-1295\"+OR+products.active_ingredients.name:\"CJC-1295\"&limit=5", "title": "Drugs@FDA — approved drug products database, queried for CJC-1295 (openFDA)", "publisher": "FDA", "date": "2026-07-16", "quote": "No matches found!" }, "verifiedAt": "2026-07-16" }, { "finding": "FDA states that it identified the potential significant safety risks it publishes for CJC-1295 in the course of reviewing the nomination to add it to the 503A or 503B bulks lists.", "note": "Recorded because it situates the CJC-1295 safety text, which the entry itself does not. It does not DATE it: the 'nominated but withdrawn' table has only two columns, 'Bulk drug substance' and 'Potential significant safety risks'. The 'Date added to category 2' column belongs to the separate category-2 table, so no date is available for the CJC-1295 entry from this page. The findings are the OUTPUT OF A NOMINATION REVIEW — FDA reviewing the case made for putting this substance on the list — not the output of a post-marketing surveillance programme or an approval review. That framing is what makes FDA's retention of the text after the nomination was withdrawn worth noting: the review that produced it is over, the nominator is gone, and FDA still publishes the risks.", "source": { "url": "https://www.fda.gov/drugs/human-drug-compounding/certain-bulk-drug-substances-use-compounding-may-present-significant-safety-risks", "title": "Certain Bulk Drug Substances for Use in Compounding that May Present Significant Safety Risks", "publisher": "FDA", "date": "2026-04-22", "quote": "FDA has identified potential significant safety risks when reviewing nominations for bulk drug substances proposed to be included on the sections 503A or 503B bulks lists." }, "verifiedAt": "2026-07-16" } ], "safetySignals": [ { "signal": "Increased heart rate and systemic vasodilatory reaction, characterised by FDA as serious adverse events associated with CJC-1295.", "note": "Attributed to FDA, which is the only body that has stated it. Route, dose, molecule (albumin-conjugating form or not), case count and source of the reports are all unstated on FDA's page; we did not find a document that supplies them.", "source": { "url": "https://www.fda.gov/drugs/human-drug-compounding/certain-bulk-drug-substances-use-compounding-may-present-significant-safety-risks", "title": "Certain Bulk Drug Substances for Use in Compounding that May Present Significant Safety Risks", "publisher": "FDA", "date": "2026-04-22", "quote": "FDA has identified serious adverse events associated with CJC-1295 including increased heart rate and systemic vasodilatory reaction." }, "verifiedAt": "2026-07-16" }, { "signal": "A peptide marketed as CJC-1295 has been sold illicitly and analysed as an unknown preparation by forensic authorities. The authors state that, as a releasing factor for growth hormone, CJC-1295 is considered a Prohibited Substance under Section S2 of the WADA Prohibited List — the list as it stood when they wrote in 2010.", "note": "Included as an identity/sourcing signal rather than a pharmacological one: what a vial labelled CJC-1295 contains has been an open question since at least 2009, and the authors reached their sequence by interpreting mass-spectrometric data from a preparation of unknown origin. On the WADA classification the paper says only 'the WADA Prohibited List', with no year attached; the 2010 attribution in the value above is ours, from the paper's publication date, and is marked as such rather than put in the authors' mouths. It matters because the WADA Prohibited List is revised annually and a 2010 paper cannot support a present-tense claim about the current one. Anyone subject to testing should check the current list rather than rely on this record.", "source": { "url": "https://pubmed.ncbi.nlm.nih.gov/21204297/", "title": "Identification of CJC-1295, a growth-hormone-releasing peptide, in an unknown pharmaceutical preparation", "publisher": "PubMed", "date": "2010-11-01", "quote": "Several peptide drugs are being manufactured illicitly, and in some cases they are being made available to the public before entering or completing clinical trials." }, "verifiedAt": "2026-07-16" } ], "faqs": [ { "question": "Is CJC-1295 legal in 2026?", "answer": "CJC-1295 is not on the FDA 503A bulks list, which means it cannot lawfully be used as a bulk drug substance to compound drug products under section 503A. Verified against the list as updated 2026-05-14: CJC-1295 appears in none of the three categories, and the string 'CJC' is absent from the document entirely. CJC-1295 also has no approved FDA application for any indication.", "source": { "url": "https://www.fda.gov/media/94155/download", "title": "Bulk Drug Substances Nominated for Use in Compounding Under Section 503A of the Federal Food, Drug, and Cosmetic Act", "publisher": "FDA", "date": "2026-05-14" }, "verifiedAt": "2026-07-16" }, { "question": "Did CJC-1295 become legal again when FDA removed it from Category 2?", "answer": "No. CJC-1295 leaving category 2 was not a legalisation event, and it was not a decision by FDA that the substance is acceptable. FDA's own page explains what happened: the substances previously in category 2 of the interim policies were withdrawn by the nominators. A nomination is a request to ADD a substance to the 503A bulks list, so withdrawing it leaves CJC-1295 off that list exactly as before — off the list means not usable in 503A compounding. FDA continues to publish, on that same page, the potential significant safety risks it identified for CJC-1295. The nomination went away; the findings did not.", "source": { "url": "https://www.fda.gov/drugs/human-drug-compounding/certain-bulk-drug-substances-use-compounding-may-present-significant-safety-risks", "title": "Certain Bulk Drug Substances for Use in Compounding that May Present Significant Safety Risks", "publisher": "FDA", "date": "2026-04-22", "quote": "This list of bulk drug substances previously in category 2 of the interim policies were withdrawn by the nominators." }, "verifiedAt": "2026-07-16" }, { "question": "Did FDA approve CJC-1295?", "answer": "No. There is no FDA-approved drug product containing CJC-1295 for any indication or route of administration — Drugs@FDA, FDA's database of approved applications, returns no matches for it. CJC-1295 never reached an approval application: the only clinical trial of CJC-1295 ever registered on ClinicalTrials.gov, a Phase 2 study sponsored by its developer ConjuChem, was terminated and posted no results.", "source": { "url": "https://api.fda.gov/drug/drugsfda.json?search=openfda.generic_name:\"cjc-1295\"+OR+products.active_ingredients.name:\"CJC-1295\"&limit=5", "title": "Drugs@FDA — approved drug products database, queried for CJC-1295 (openFDA)", "publisher": "FDA", "date": "2026-07-16", "quote": "No matches found!" }, "verifiedAt": "2026-07-16" }, { "question": "Is there any human evidence that CJC-1295 works?", "answer": "There are human trials of CJC-1295, but none of them measured whether it helps anyone. In two randomised, placebo-controlled, double-blind ascending-dose trials published in 2006 (PMID 16352683, healthy adults aged 21-61, 28 and 49 days), researchers administered CJC-1295 subcutaneously and reported dose-dependent increases in mean plasma growth hormone and IGF-I. The trials' own stated main outcome measures were peak concentrations and area under the curve of GH and IGF-I — hormone levels, which are a pharmacodynamic effect rather than a clinical benefit. The authors concluded only that their data support the potential utility of CJC-1295 as a therapeutic agent. No trial of CJC-1295 has ever reported a clinical outcome, and none is indexed for the uses it is marketed for.", "source": { "url": "https://pubmed.ncbi.nlm.nih.gov/16352683/", "title": "Prolonged stimulation of growth hormone (GH) and insulin-like growth factor I secretion by CJC-1295, a long-acting analog of GH-releasing hormone, in healthy adults", "publisher": "PubMed", "date": "2006-03-01", "quote": "The main outcome measures were peak concentrations and area under the curve of GH and IGF-I; standard pharmacokinetic parameters were used for CJC-1295." }, "verifiedAt": "2026-07-16" }, { "question": "Was CJC-1295 ever tested in patients rather than healthy volunteers?", "answer": "Once, and it did not finish. ConjuChem registered a randomised, double-blind, placebo-controlled Phase 2 trial of CJC-1295 in HIV patients with visceral obesity (NCT00267527, 12 weeks, registered enrolment 120 — the registry does not state whether that is the anticipated or the actual number, and the trial did not finish). Its registered title describes it as a study 'to Evaluate the Efficacy and Safety of CJC 1295'. Its overall status on ClinicalTrials.gov is TERMINATED, it posted no results, and its last update was in October 2006. The registry record carries no why-stopped information, so the reason it was terminated is not publicly known. It is the only trial of CJC-1295 registered on ClinicalTrials.gov.", "source": { "url": "https://clinicaltrials.gov/study/NCT00267527", "title": "A Study to Evaluate CJC 1295 in HIV Patients With Visceral Obesity (NCT00267527)", "publisher": "ClinicalTrials.gov", "date": "2006-10-16", "quote": "A Multicenter, Randomized, Placebo-Controlled, Double-Blind, Phase 2 Study to Evaluate the Efficacy and Safety of CJC 1295 Administered for 12 Weeks in HIV Infected Patients With HIV Associated Visceral Obesity" }, "verifiedAt": "2026-07-16" }, { "question": "Is CJC-1295 safe?", "answer": "Unknown, and the two public records disagree. FDA states that it has identified serious adverse events associated with CJC-1295 including increased heart rate and systemic vasodilatory reaction, and that available clinical data are limited. The 2006 healthy-adult trials report the opposite experience — no serious adverse reactions were reported (PMID 16352683). These cannot be reconciled from public documents: FDA does not state the source, dates, route, case count or molecule for the events it describes. Separately, FDA states that compounded drugs containing CJC-1295 may pose risk for immunogenicity for certain routes of administration and may have complexities regarding peptide-related impurities and API characterization — a concern about what is in the vial, which a forensic analysis of a preparation sold as CJC-1295 (PMID 21204297) makes concrete.", "source": { "url": "https://www.fda.gov/drugs/human-drug-compounding/certain-bulk-drug-substances-use-compounding-may-present-significant-safety-risks", "title": "Certain Bulk Drug Substances for Use in Compounding that May Present Significant Safety Risks", "publisher": "FDA", "date": "2026-04-22", "quote": "FDA has identified serious adverse events associated with CJC-1295 including increased heart rate and systemic vasodilatory reaction. Available clinical data are limited." }, "verifiedAt": "2026-07-16" } ] }, { "slug": "desmopressin", "name": "Desmopressin", "aliases": [ "DDAVP", "dDAVP", "desmopressin acetate", "1-desamino-8-D-arginine vasopressin", "Stimate", "Desmoda", "Noctiva", "Nocdurna", "Minirin", "Concentraid" ], "url": "https://peptides101.com/compounds/desmopressin", "moleculeNote": "A synthetic analogue of the endogenous nonapeptide arginine vasopressin (antidiuretic hormone). Every desmopressin product FDA has approved contains the ACETATE salt, and the labels state strengths in both acetate and desmopressin-base terms — NOCTIVA's label, for example, describes its spray as delivering desmopressin acetate 'equivalent to' a smaller quantity of desmopressin. The disambiguation that matters on this record is not the salt and not the sequence: it is the ROUTE. FDA has approved tablets, an oral solution, a sublingual tablet, an injection and several nasal sprays of the same active ingredient, and their approved indications, their limitations of use and even whether they carry a boxed warning differ from one presentation to the next. 'Desmopressin' does not identify a product.", "quickAnswer": "Desmopressin is an FDA-approved vasopressin analogue, marketed since an initial U.S. approval in 1978 and still gaining approvals — FDA approved DESMODA (desmopressin acetate) oral solution under NDA 219873 on 25 February 2026 for central diabetes insipidus. Its approved indications differ by ROUTE rather than by molecule: DDAVP tablets (NDA 019955) are indicated for central diabetes insipidus and for primary nocturnal enuresis, while desmopressin acetate injection (NDA 018938) is indicated for central diabetes insipidus, hemophilia A and von Willebrand's disease Type I in patients with factor VIII levels greater than 5%. The DDAVP Nasal Spray label states the spray 'is not an indicated formulation for the treatment of primary nocturnal enuresis due to a higher risk of hyponatremia and hyponatremic convulsions with the use of the nasal spray formulation compared to desmopressin tablets seen in postmarketing reports' — the same molecule, approved for bedwetting by one route and excluded from it by another. The two products FDA approved specifically for nocturia due to nocturnal polyuria, NOCTIVA (NDA 201656, 2017) and NOCDURNA (NDA 022517, 2018), are both listed Discontinued on Drugs@FDA. Desmopressin acetate injection carries a boxed warning for hyponatremia, which the label states can be life-threatening if severe, leading to seizures, coma, respiratory arrest or death; the DDAVP tablets label carries hyponatremia as an ordinary warning with no boxed warning. In 2020 Ferring recalled all marketed lots of three desmopressin nasal sprays to the consumer level for superpotency, and FDA's Enforcement Report classified all three recalls Class I.", "fdaStatus": { "value": "approved", "note": "FDA-approved, and not only historically — the source here is an FDA approval letter dated 2026-02-25, for a desmopressin acetate product approved this year. The labels record an 'Initial U.S. Approval: 1978'. Cross-checked against Drugs@FDA on 2026-08-02 via the openFDA `drug/drugsfda` endpoint: 38 applications contain desmopressin acetate as an active ingredient, and products under NDA 019955 (DDAVP tablets), NDA 018938 (desmopressin acetate injection), NDA 020355 (STIMATE) and NDA 219873 (DESMODA), plus numerous ANDAs, are present. Approval is always for a specific product, indication and population — read the approval record below, because on this molecule the indications differ by ROUTE.", "source": { "url": "https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2026/219873Orig1s000ltr.pdf", "title": "NDA 219873 approval letter — Desmoda (desmopressin acetate) oral solution", "publisher": "FDA", "date": "2026-02-25", "quote": "Please refer to your new drug application (NDA) received April 25, 2025, and your amendments, submitted pursuant to section 505(b)(2) of the Federal Food, Drug, and Cosmetic Act (FDCA) for Desmoda (desmopressin acetate) oral solution. … We have completed our review of this application, as amended. It is approved, effective on the date of this letter, for use as recommended in the enclosed agreed-upon labeling." }, "verifiedAt": "2026-08-02" }, "compoundingStatus": null, "evidence": { "tier": "proven-in-humans", "humanAdministrationChecked": true, "note": "ADMINISTRATION CHECK RUN, NOT ASSUMED. Four randomised placebo-controlled trials were opened in FDA-approved labeling on 2026-08-02, and in every one desmopressin acetate was ADMINISTERED to human participants who were randomised to it against placebo. It was not measured as an endogenous biomarker — the trap that reduces MOTS-c and TB-500 from an apparent five human RCTs to an actual zero. Named, so the claim is checkable: NOCDURNA Study 1 (237 women randomised, sublingual desmopressin acetate versus placebo, 3 months) and Study 2 (230 men, same design), both in section 14 of the NDA 022517 label; NOCTIVA Trial 1 (612 patients randomised across two active arms and placebo, 12 weeks) and Trial 2 (433 patients, same design), both in section 14 of the NDA 201656 label. READ THE EFFECT SIZES BEFORE READING THE TIER. In NOCDURNA Study 1 the difference from placebo in mean nocturnal voids per night was -0.3 (95% CI -0.5 to -0.1) and in Study 2 -0.4 (95% CI -0.6 to -0.2), from baselines of about three voids per night; the odds ratios for 33% responder status were 2.15 (95% CI 1.36 to 3.41) and 2.02 (95% CI 1.30 to 3.14). NOCTIVA's two trials reported differences from placebo of -0.3 and -0.4 nocturic episodes per night. Statistically separated from placebo, and small. Both products are now listed Discontinued on Drugs@FDA. SCOPE, and it is narrow. This tier attaches to approved desmopressin acetate products used for their approved indications. It does not transfer between routes: FDA's own labeling states that the nasal spray is not an indicated formulation for primary nocturnal enuresis while the tablets are indicated for it, so 'desmopressin works' is not a statement any single trial supports. AN HONEST GAP: the central diabetes insipidus, hemophilia A and von Willebrand's disease Type I indications rest on evidence generated around the 1978 initial U.S. approval. That evidence was NOT opened for this record. Those indications are recorded here from the approved labels, which is a regulatory fact, not a study this record has verified.", "source": { "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/022517s000lbl.pdf", "title": "NOCDURNA (desmopressin acetate) sublingual tablets — Highlights of Prescribing Information (NDA 022517, original approval)", "publisher": "FDA", "date": "2018-06-21", "quote": "The efficacy of NOCDURNA in the treatment of adults with nocturia due to nocturnal polyuria was established in two 3-month randomized, double-blind, placebo-controlled, multicenter trials in adults over 18 years of age. Study 1 enrolled only women and Study 2 enrolled only men." }, "verifiedAt": "2026-08-02" }, "fdaApproval": { "applicationNumber": "NDA 019955 (DDAVP tablets); NDA 018938 (desmopressin acetate injection); NDA 017922 (DDAVP Nasal Spray); NDA 020355 (STIMATE nasal spray); NDA 219873 (DESMODA oral solution); NDA 201656 (NOCTIVA nasal spray); NDA 022517 (NOCDURNA sublingual tablets); plus numerous ANDAs", "brandName": "DDAVP, Stimate, Desmoda, Noctiva, Nocdurna, Minirin, Concentraid", "approvedIndication": "Central Diabetes Insipidus: DDAVP Tablets are indicated as antidiuretic replacement therapy in the management of central diabetes insipidus and for the management of the temporary polyuria and polydipsia following head trauma or surgery in the pituitary region. DDAVP is ineffective for the treatment of nephrogenic diabetes insipidus. Patients were selected for therapy based on the diagnosis by means of the water deprivation test, the hypertonic saline infusion test, and/or response to antidiuretic hormone. Continued response to DDAVP can be monitored by measuring urine volume and osmolality. Primary Nocturnal Enuresis: DDAVP Tablets are indicated for the management of primary nocturnal enuresis. DDAVP may be used alone or as an adjunct to behavioral conditioning or other non-pharmacologic intervention.", "discontinued": false, "discontinuedNote": "`discontinued` is false because desmopressin as a franchise is marketed — DDAVP tablets, desmopressin acetate injection, generic nasal sprays and the 2026-approved DESMODA oral solution all carry a Prescription marketing status on Drugs@FDA. Individual products under this molecule ARE discontinued, and which ones is the interesting part: NOCTIVA (NDA 201656) and NOCDURNA (NDA 022517) — the only two products FDA ever approved for nocturia due to nocturnal polyuria — are both listed Discontinued, as are MINIRIN (NDA 021333), CONCENTRAID (NDA 019776), the DDAVP Nasal Spray products under NDA 017922 and the STIMATE products under NDA 020355. Each is recorded with its own source below.", "source": { "url": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=6d55baa9-2b62-469c-93ae-3909ab249332", "title": "DDAVP (desmopressin acetate) tablets — full prescribing information (SPL, NDA 019955)", "publisher": "DailyMed (U.S. National Library of Medicine)", "date": "2021-02-03" }, "verifiedAt": "2026-08-02" }, "fdaFindings": [ { "finding": "Desmopressin acetate injection (NDA 018938) is indicated for central (cranial) diabetes insipidus and for the management of the temporary polyuria and polydipsia following head trauma or surgery in the pituitary region; for hemophilia A in patients with factor VIII coagulant activity levels greater than 5%, to maintain hemostasis during surgical procedures and postoperatively or reduce bleeding with episodes of spontaneous or traumatic injuries; and for von Willebrand's disease (Type I) in patients with mild to moderate disease with factor VIII levels greater than 5%. The label states it is ineffective and not indicated for nephrogenic diabetes insipidus, and not indicated for severe Type I von Willebrand's disease or where there is evidence of an abnormal molecular form of factor VIII antigen.", "note": "The haematology half of this molecule's identity, and the gating is easy to miss. Both bleeding-disorder indications are restricted to patients with factor VIII levels above 5%, and the label carves out severe Type I von Willebrand's disease explicitly. This is not a general haemostatic agent. PROVENANCE, because the record would otherwise look inconsistent: Drugs@FDA lists the brand name on this NDA as DDAVP with sponsor 'J MOLNER', while the current SPL is published as 'Desmopressin Acetate injection' by Nordic Pharma. The indications text above was confirmed in both the 2022 accessdata label PDF cited here and the current SPL (effective 2025-10-23) read via openFDA `drug/label` on 2026-08-02.", "source": { "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/018938Orig1s039lbl.pdf", "title": "DDAVP (desmopressin acetate) injection — Highlights of Prescribing Information (NDA 018938, supplement 39)", "publisher": "FDA", "date": "2022-07-21", "quote": "DDAVP Injection is a vasopressin analog used for: • Central Diabetes Insipidus … • Hemophilia A - for patients with factor VIII coagulant activity levels greater than 5% to maintain hemostasis during surgical procedures and postoperatively or reduce bleeding with episodes of spontaneous or traumatic injuries such as hemarthroses, intramuscular hematomas, or mucosal bleeding. • von Willebrand's disease (Type I) - for patients with mild to moderate disease with factor VIII levels greater than 5% …" }, "verifiedAt": "2026-08-02" }, { "finding": "The FDA-approved labeling for DDAVP Nasal Spray (NDA 017922) states that the product is NOT indicated for the treatment of primary nocturnal enuresis, and gives the reason: a higher risk of hyponatremia and hyponatremic convulsions with the nasal spray formulation compared with desmopressin tablets, seen in postmarketing reports.", "note": "The single most useful finding on this record, and the site's thesis stated by FDA about an approved drug rather than about a research chemical. Same active ingredient, same indication sought, two routes — and FDA's labeling approves one and expressly excludes the other, on postmarketing harm. Anyone reasoning 'the tablets are approved for bedwetting, so the spray must be fine for it' is contradicted by the spray's own label. SCOPE: verified in the NDA 017922 reference label cited here. The currently marketed generic desmopressin acetate nasal spray SPL (ANDA 074830, Bausch, effective 2025-06-19) was read on 2026-08-02 and carries the identical Limitation of Use, so this is not an artifact of a discontinued brand label.", "source": { "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/017922s046lbl.pdf", "title": "DDAVP (desmopressin acetate) nasal spray — Highlights of Prescribing Information (NDA 017922, supplement 46)", "publisher": "FDA", "date": "2018-10-22", "quote": "DDAVP Nasal Spray is not an indicated formulation for the treatment of primary nocturnal enuresis due to a higher risk of hyponatremia and hyponatremic convulsions with the use of the nasal spray formulation compared to desmopressin tablets seen in postmarketing reports." }, "verifiedAt": "2026-08-02" }, { "finding": "STIMATE nasal spray (NDA 020355) is indicated only for hemophilia A and for von Willebrand's disease (Type I), each restricted to patients with factor VIII levels greater than 5%. It carries no diabetes insipidus indication and no nocturia or enuresis indication.", "note": "Two nasal sprays of the same active ingredient, sold under the same sponsor, with non-overlapping indications: DDAVP Nasal Spray is approved for central diabetes insipidus and STIMATE is not; STIMATE is approved for hemophilia A and von Willebrand's disease and DDAVP Nasal Spray is not. They differ in concentration, and the label identifies STIMATE as a 150 mcg per 0.1 mL spray in a 2.5 mL bottle. 'Desmopressin nasal spray' names neither product.", "source": { "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2026/020355s022lbl.pdf", "title": "STIMATE (desmopressin acetate) nasal spray — Highlights of Prescribing Information (NDA 020355, supplement 22)", "publisher": "FDA", "date": "2026-07-15", "quote": "STIMATE is a vasopressin analog used for: • Hemophilia A - for patients with factor VIII coagulant activity levels greater than 5% … • von Willebrand's disease (Type I) - for patients with mild to moderate disease with factor VIII levels greater than 5% … Limitations of Use STIMATE is not indicated for: • von Willebrand's disease (severe Type I) …" }, "verifiedAt": "2026-08-02" }, { "finding": "A MARKETING-STATUS CONTRADICTION IN FDA'S OWN RECORDS, unresolved. Drugs@FDA lists both STIMATE products under NDA 020355 as Discontinued. In the same period FDA approved supplement 22 to that NDA on 2026-07-15, a new STIMATE prescribing information was published with an effective date of 2026-07-22, and the FDA National Drug Code Directory carries an active Stimate listing (NDC 55566-3000, Ferring Pharmaceuticals Inc., marketing start 2025-06-25, listing expiration 2027-12-31) with no marketing end date.", "note": "Recorded as a contradiction rather than resolved, because resolving it would mean guessing. The most likely reading is that the Drugs@FDA product rows still describe the older CSL Behring presentation (NDC 0053-6871, the one recalled in 2020) while Ferring has relisted the product under a new NDC — but that is an inference, not a document. What is documented: the discontinuation flag and the active NDC listing are both current FDA records and they disagree. Verified 2026-08-02 against the Drugs@FDA overview page cited here, the openFDA `drug/drugsfda` record for NDA 020355, the openFDA `drug/ndc` record for NDC 55566-3000, and the supplement 22 label PDF. Anyone relying on STIMATE availability should check with the sponsor rather than with this record.", "source": { "url": "https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=020355", "title": "Drugs@FDA — NDA 020355 (STIMATE), products and marketing status", "publisher": "FDA", "date": "2026-07-15" }, "verifiedAt": "2026-08-02" }, { "finding": "NOCTIVA (desmopressin acetate) nasal spray was approved on 2017-03-03 under NDA 201656 as a vasopressin analog indicated for the treatment of nocturia due to nocturnal polyuria in adults who awaken at least 2 times per night to void, with a Limitation of Use that it was not studied in patients younger than 50 years of age. Drugs@FDA lists both NOCTIVA products as Discontinued.", "note": "Read the indication precisely, because 'approved for nocturia' is not what it says. The approval is for nocturia DUE TO NOCTURNAL POLYURIA — one cause among many — and the label says so in terms: 'Many conditions can cause nocturia. The efficacy and safety of NOCTIVA have not been established for all causes of nocturia.' The label also carried a boxed warning for hyponatremia. The Discontinued status is from the Drugs@FDA overview page for NDA 201656, fetched 2026-08-02; it is a marketing fact and this record does not claim to know the sponsor's reason for it.", "source": { "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/201656lbl.pdf", "title": "NOCTIVA (desmopressin acetate) nasal spray — Highlights of Prescribing Information (NDA 201656, original approval)", "publisher": "FDA", "date": "2017-03-03", "quote": "NOCTIVA is a vasopressin analog indicated for the treatment of nocturia due to nocturnal polyuria in adults who awaken at least 2 times per night to void. (1) Limitation of Use: Not studied in patients younger than 50 years of age. (1)" }, "verifiedAt": "2026-08-02" }, { "finding": "NOCDURNA (desmopressin acetate) sublingual tablets were approved on 2018-06-21 under NDA 022517 as a vasopressin analog indicated for the treatment of nocturia due to nocturnal polyuria in adults who awaken at least 2 times per night to void. Drugs@FDA lists both NOCDURNA products as Discontinued.", "note": "The second and last of FDA's nocturia-specific desmopressin approvals, and it is also listed Discontinued. NOCDURNA's label likewise states that 'Many conditions can cause nocturia' and that its efficacy and safety 'have not been established for the treatment of all causes of nocturia'. It carried a boxed warning for hyponatremia and an unusually long contraindication list including heart failure, uncontrolled hypertension, polydipsia, SIADH and an estimated glomerular filtration rate below 50 mL/min/1.73 m2. Discontinued status verified on the Drugs@FDA overview page for NDA 022517, 2026-08-02.", "source": { "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/022517s000lbl.pdf", "title": "NOCDURNA (desmopressin acetate) sublingual tablets — Highlights of Prescribing Information (NDA 022517, original approval)", "publisher": "FDA", "date": "2018-06-21", "quote": "NOCDURNA is a vasopressin analog indicated for the treatment of nocturia due to nocturnal polyuria in adults who awaken at least 2 times per night to void. (1)" }, "verifiedAt": "2026-08-02" }, { "finding": "FDA approved DESMODA (desmopressin acetate) oral solution on 2026-02-25 under NDA 219873, submitted pursuant to section 505(b)(2), indicated for the management of central diabetes insipidus as antidiuretic replacement therapy for adults and pediatric patients, and not indicated for nephrogenic diabetes insipidus.", "note": "The newest desmopressin approval, and worth recording because it shows the direction of travel. A molecule approved in 1978 gained a NEW presentation in 2026 — and that presentation was approved for the narrowest of the historical indications, central diabetes insipidus alone. It carries no enuresis, nocturia, hemophilia or von Willebrand's indication. Approval pathway confirmed in the FDA approval letter: a 505(b)(2) application received 2025-04-25 from Eton Pharmaceuticals.", "source": { "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2026/219873Orig1s000lbl.pdf", "title": "DESMODA (desmopressin acetate) oral solution — Highlights of Prescribing Information (NDA 219873)", "publisher": "FDA", "date": "2026-02-25", "quote": "DESMODA is a vasopressin analog indicated for the management of central diabetes insipidus as antidiuretic replacement therapy for adults and pediatric patients. Limitations of Use • DESMODA is not indicated for the treatment of nephrogenic diabetes insipidus." }, "verifiedAt": "2026-08-02" }, { "finding": "Desmopressin appears nowhere in FDA's list of bulk drug substances nominated for use in compounding under section 503A, updated 2026-05-14 — not in Category 1, Category 2 or Category 3.", "note": "Recorded to close a misreading, not to assert a status, and the difference matters. Verified by fetching and text-extracting the document directly on 2026-08-02: zero hits for 'desmopressin' anywhere in it. This absence means something entirely different from BPC-157's absence. The 503A nomination list is a route for substances that are NOT components of approved drug products; desmopressin acetate is a component of dozens. Its absence is the same kind of absence as bremelanotide's — it was never on that track — and it is neither a permission nor a safety finding. This record therefore carries no compoundingStatus at all, because asserting 'never-nominated' would imply a proceeding desmopressin was never part of.", "source": { "url": "https://www.fda.gov/media/94155/download", "title": "Bulk Drug Substances Nominated for Use in Compounding Under Section 503A of the Federal Food, Drug, and Cosmetic Act", "publisher": "FDA", "date": "2026-05-14" }, "verifiedAt": "2026-08-02" } ], "safetySignals": [ { "signal": "Boxed warning — HYPONATREMIA, on desmopressin acetate injection (NDA 018938). The label states the drug can cause hyponatremia, which may be life-threatening if severe, and that it is contraindicated in patients at increased risk of severe hyponatremia, such as patients with excessive fluid intake, illnesses that can cause fluid or electrolyte imbalances, and in those using loop diuretics or systemic or inhaled glucocorticoids.", "note": "FDA's highest-level warning, and the reason this record insists on naming products rather than the molecule. The boxed warning is NOT uniform across desmopressin: it appears on the injection, on NOCTIVA and on NOCDURNA, and the DDAVP tablets label (NDA 019955) carries hyponatremia in an ordinary WARNINGS section with no boxed warning at all. Both labels were read on 2026-08-02. The boxed warning also requires serum sodium monitoring before and during treatment — a screening step nobody obtaining an unprescribed product is asked to take, because there is no prescriber to ask it. The elisions above remove specific monitoring intervals under this site's no-dosing policy; no finding depends on them.", "source": { "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/018938Orig1s039lbl.pdf", "title": "DDAVP (desmopressin acetate) injection — Highlights of Prescribing Information (NDA 018938, supplement 39)", "publisher": "FDA", "date": "2022-07-21", "quote": "WARNING: HYPONATREMIA … DDAVP can cause hyponatremia, which may be life-threatening if severe. (5.1) • DDAVP is contraindicated in patients at increased risk of severe hyponatremia, such as patients with excessive fluid intake, illnesses that can cause fluid or electrolyte imbalances, and in those using loop diuretics or systemic or inhaled glucocorticoids. (4, 5.1) … • If hyponatremia occurs, interrupt or discontinue DDAVP. (5.1)" }, "verifiedAt": "2026-08-02" }, { "signal": "The full prescribing information for desmopressin acetate states that severe hyponatremia can be life-threatening, leading to seizures, coma, respiratory arrest, or death.", "note": "Stated plainly because desmopressin is frequently described as a benign, long-established drug, and the mechanism of harm is not intuitive. The risk is not toxicity of the peptide — it is water retention. The labels attribute hyponatremia to excessive fluid intake while urine output is limited by the antidiuretic effect, which is why every label carries a fluid-restriction instruction and why the pediatric and geriatric warnings are the strongest. The quote above is from the current SPL wording read via openFDA `drug/label` on 2026-08-02; the 2022 label PDF cited here carries the same finding in the boxed warning and section 5.1.", "source": { "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/018938Orig1s039lbl.pdf", "title": "DDAVP (desmopressin acetate) injection — Highlights of Prescribing Information (NDA 018938, supplement 39)", "publisher": "FDA", "date": "2022-07-21", "quote": "Desmopressin acetate injection can cause hyponatremia. Severe hyponatremia can be life-threatening if it is not promptly diagnosed and treated, leading to seizures, coma, respiratory arrest, or death" }, "verifiedAt": "2026-08-02" }, { "signal": "CLASS I RECALL, 2020. Ferring Pharmaceuticals US voluntarily recalled all lots on the market of DDAVP Nasal Spray 10 mcg/0.1 mL, Desmopressin Acetate Nasal Spray 10 mcg/0.1 mL and STIMATE Nasal Spray 1.5 mg/mL to the consumer level, due to superpotency — amounts of desmopressin higher than specified, found during routine testing. FDA's Enforcement Report classifies all three recalls as Class I.", "note": "A manufacturing failure at an approved, decades-old product, which is the honest counterweight to this record's own framing. Approval buys you a specification and a recall mechanism; it does not buy you a guarantee that every vial met the spec. What it does buy is that the deviation was found in routine testing, published, classified and acted on — none of which exists for an unapproved product. Note the company's own statement of the harm: 'To date, Ferring has not received an increase in adverse event reports due to increased concentrations of desmopressin from users of the nasal spray. A single non-fatal adverse event potentially associated with this issue was reported in the US during the timeframe that the affected product was distributed.' This is a company announcement that FDA posts as a public service; FDA states it does not endorse either the product or the company.", "source": { "url": "https://www.fda.gov/safety/recalls-market-withdrawals-safety-alerts/ferring-us-issues-voluntary-nationwide-recall-ddavpr-nasal-spray-10-mcg01ml-desmopressin-acetate", "title": "Ferring US Issues Voluntary Nationwide Recall of DDAVP Nasal Spray, Desmopressin Acetate Nasal Spray and STIMATE Nasal Spray Due to Superpotency", "publisher": "FDA", "date": "2020-08-05", "quote": "These products are being recalled due to superpotency or amounts of desmopressin higher than specified. These out of specification results were obtained during routine testing. The risks associated with higher than specified amounts of desmopressin relate to abnormally low levels of sodium in the blood (i.e., hyponatremia) which could eventually lead to seizure, coma, and death." }, "verifiedAt": "2026-08-02" }, { "signal": "FDA's Enforcement Report records three Class I recalls initiated 2020-07-21 for 'Superpotent Drug', covering 29,371 STIMATE nasal sprays (D-1506-2020), 184,325 desmopressin acetate nasal sprays (D-1505-2020) and 15,175 DDAVP nasal sprays (D-1504-2020), all distributed nationwide within the United States. All three were terminated 2023-10-13.", "note": "Recorded separately from the company announcement because it carries what the announcement does not: FDA's own classification and the quantities. Class I is FDA's most serious recall class. The three recall numbers together cover 228,871 units. Verified via the openFDA `drug/enforcement` endpoint on 2026-08-02; the URL cited is the exact query returning record D-1506-2020.", "source": { "url": "https://api.fda.gov/drug/enforcement.json?search=recall_number:\"D-1506-2020\"", "title": "FDA Enforcement Report — recall D-1506-2020 (STIMATE nasal spray), with companion recalls D-1504-2020 and D-1505-2020", "publisher": "FDA", "date": "2020-08-26", "quote": "Superpotent Drug" }, "verifiedAt": "2026-08-02" }, { "signal": "Labeled warnings and precautions for desmopressin acetate injection, beyond hyponatremia, include hypotension with compensatory increase in heart rate or hypertension; increased risk of thrombosis in patients with von Willebrand's disease Type IIB, due to platelet aggregation; severe hypersensitivity reactions; and fluid retention, with the label stating it is not recommended in patients at risk for increased intracranial pressure or with a history of urinary retention.", "note": "The Type IIB von Willebrand's signal deserves separate attention because it inverts the indication: desmopressin is approved for Type I von Willebrand's disease and the label makes Type IIB a contraindication on the injection, on the basis of thrombosis from platelet aggregation. A patient who knows only that 'desmopressin treats von Willebrand's' has the subtype backwards half the time. Verified in both the 2022 label PDF cited here and the current SPL read via openFDA `drug/label` on 2026-08-02.", "source": { "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/018938Orig1s039lbl.pdf", "title": "DDAVP (desmopressin acetate) injection — Highlights of Prescribing Information (NDA 018938, supplement 39)", "publisher": "FDA", "date": "2022-07-21", "quote": "Increased Risk of Thrombosis in Patients with von Willebrand's Disease Type IIB : Use of desmopressin acetate in patients with Type IIB von Willebrand's disease may cause thrombosis due to platelet aggregation. (5.3)" }, "verifiedAt": "2026-08-02" }, { "signal": "The FDA-approved labeling for DDAVP Nasal Spray states that chronic administration may result in changes to nasal mucosa, and that nasal mucosa abnormalities such as scarring and edema — whether from chronic administration or other causes including nasal blockage, mucosal atrophy, severe atrophic rhinitis or recent nasal surgery — may cause erratic, unreliable absorption.", "note": "A route-specific failure mode with no equivalent for the tablets, and one that compounds the superpotency problem: a product whose absorption is described by its own label as potentially 'erratic, unreliable' is a product where the amount actually delivered is uncertain in both directions. The label's own remedy is to avoid the nasal route in such patients and consider other formulations of desmopressin acetate given by other routes.", "source": { "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/017922s046lbl.pdf", "title": "DDAVP (desmopressin acetate) nasal spray — Highlights of Prescribing Information (NDA 017922, supplement 46)", "publisher": "FDA", "date": "2018-10-22", "quote": "Chronic administration of DDAVP Nasal Spray may result in changes to nasal mucosa. Nasal mucosa abnormalities (such as scarring and edema) due to chronic administration, or due to other causes … may cause erratic, unreliable absorption." }, "verifiedAt": "2026-08-02" } ], "faqs": [ { "question": "Is desmopressin FDA-approved?", "answer": "Yes. Desmopressin acetate is the active ingredient in multiple FDA-approved drug products, and the approvals are current rather than merely historical: FDA approved DESMODA (desmopressin acetate) oral solution under NDA 219873 on 25 February 2026, on a 505(b)(2) application from Eton Pharmaceuticals received 25 April 2025. The approval letter states the application 'is approved, effective on the date of this letter, for use as recommended in the enclosed agreed-upon labeling.' The labels record an initial U.S. approval in 1978. Other currently marketed applications include DDAVP tablets (NDA 019955), desmopressin acetate injection (NDA 018938) and generic nasal sprays, alongside numerous ANDAs. Approval is always for a specific product and a specific indication, and on this molecule those indications differ by route of administration — the tablets, the injection, the nasal sprays and the oral solution are not approved for the same things.", "source": { "url": "https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2026/219873Orig1s000ltr.pdf", "title": "NDA 219873 approval letter — Desmoda (desmopressin acetate) oral solution", "publisher": "FDA", "date": "2026-02-25", "quote": "This NDA provides for the use of Desmoda (desmopressin acetate) oral solution for the management of central diabetes insipidus as antidiuretic replacement therapy for adults and pediatric patients. … It is approved, effective on the date of this letter, for use as recommended in the enclosed agreed-upon labeling." }, "verifiedAt": "2026-08-02" }, { "question": "Can desmopressin nasal spray be used for bedwetting?", "answer": "Not according to its label. DDAVP Nasal Spray's FDA-approved labeling lists primary nocturnal enuresis under Limitations of Use and gives the reason in section 5.1: 'DDAVP Nasal Spray is not an indicated formulation for the treatment of primary nocturnal enuresis due to a higher risk of hyponatremia and hyponatremic convulsions with the use of the nasal spray formulation compared to desmopressin tablets seen in postmarketing reports.' DDAVP tablets ARE indicated for primary nocturnal enuresis. So the same active ingredient is approved for this use by one route and excluded from it by another, on the basis of harm reported after marketing — which means an inference from the tablets to the spray runs directly against FDA's labeling. The marketed generic desmopressin acetate nasal spray carries the identical limitation. Whether any desmopressin product is appropriate for a particular patient is a decision for a licensed prescriber.", "source": { "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/017922s046lbl.pdf", "title": "DDAVP (desmopressin acetate) nasal spray — Highlights of Prescribing Information (NDA 017922, supplement 46)", "publisher": "FDA", "date": "2018-10-22", "quote": "DDAVP Nasal Spray is not indicated for: • Treatment of nephrogenic diabetes insipidus, • Treatment of primary nocturnal enuresis [see Warnings and Precautions (5.1)] …" }, "verifiedAt": "2026-08-02" }, { "question": "Is desmopressin approved for nocturia?", "answer": "It was, twice, and both products are now listed as Discontinued on Drugs@FDA. FDA approved NOCTIVA (desmopressin acetate) nasal spray under NDA 201656 on 3 March 2017 and NOCDURNA (desmopressin acetate) sublingual tablets under NDA 022517 on 21 June 2018, each 'indicated for the treatment of nocturia due to nocturnal polyuria in adults who awaken at least 2 times per night to void'. As of 2 August 2026 the Drugs@FDA overview pages for both applications list every product under them with a marketing status of Discontinued. Two things are worth reading precisely. First, the indication was never 'nocturia' — it was nocturia due to nocturnal polyuria, and both labels state that many conditions can cause nocturia and that efficacy and safety were not established for all of them. Second, both labels carried a boxed warning for hyponatremia. Drugs@FDA records a marketing status, not a reason; this record does not claim to know why either product was discontinued.", "source": { "url": "https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=022517", "title": "Drugs@FDA — NDA 022517 (NOCDURNA), products and marketing status", "publisher": "FDA", "date": "2018-06-21" }, "verifiedAt": "2026-08-02" }, { "question": "Does desmopressin have a boxed warning?", "answer": "It depends on the product, which is the answer people most often get wrong. Desmopressin acetate injection (NDA 018938) carries a boxed warning headed WARNING: HYPONATREMIA, stating the drug 'can cause hyponatremia, which may be life-threatening if severe' and that it is contraindicated in patients at increased risk of severe hyponatremia — including those with excessive fluid intake, illnesses that can cause fluid or electrolyte imbalances, and those using loop diuretics or systemic or inhaled glucocorticoids. The withdrawn nocturia products NOCTIVA and NOCDURNA carried the same boxed warning. The DDAVP tablets label (NDA 019955) does NOT carry a boxed warning: it describes hyponatremia in an ordinary WARNINGS section, noting that desmopressin 'is a potent antidiuretic which, when administered, may lead to water intoxication and/or hyponatremia' and that 'Unless properly diagnosed and treated hyponatremia can be fatal.' The risk is present across the molecule; the regulatory prominence given to it is not uniform, so read the label of the product in hand rather than a label for 'desmopressin'.", "source": { "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/018938Orig1s039lbl.pdf", "title": "DDAVP (desmopressin acetate) injection — Highlights of Prescribing Information (NDA 018938, supplement 39)", "publisher": "FDA", "date": "2022-07-21", "quote": "WARNING: HYPONATREMIA See full prescribing information for complete boxed warning. • DDAVP can cause hyponatremia, which may be life-threatening if severe. (5.1)" }, "verifiedAt": "2026-08-02" }, { "question": "Was desmopressin nasal spray recalled?", "answer": "Yes. On 5 August 2020 FDA posted Ferring Pharmaceuticals US's announcement that it was voluntarily recalling all lots on the market of DDAVP Nasal Spray 10 mcg/0.1 mL, Desmopressin Acetate Nasal Spray 10 mcg/0.1 mL and STIMATE Nasal Spray 1.5 mg/mL to the consumer level, because the products were superpotent — containing 'amounts of desmopressin higher than specified', found during routine testing. The announcement states the risk relates to hyponatremia 'which could eventually lead to seizure, coma, and death', and that a single non-fatal adverse event potentially associated with the issue was reported in the US while the affected product was distributed. FDA's own Enforcement Report classified all three recalls as Class I, its most serious class, initiated 21 July 2020 and terminated 13 October 2023, covering 228,871 nasal sprays across recall numbers D-1504-2020, D-1505-2020 and D-1506-2020. FDA posts company recall announcements as a public service and states it does not endorse either the product or the company.", "source": { "url": "https://www.fda.gov/safety/recalls-market-withdrawals-safety-alerts/ferring-us-issues-voluntary-nationwide-recall-ddavpr-nasal-spray-10-mcg01ml-desmopressin-acetate", "title": "Ferring US Issues Voluntary Nationwide Recall of DDAVP Nasal Spray, Desmopressin Acetate Nasal Spray and STIMATE Nasal Spray Due to Superpotency", "publisher": "FDA", "date": "2020-08-05", "quote": "Ferring Pharmaceuticals US is voluntarily recalling all lots on the market of DDAVP® Nasal Spray 10 mcg/0.1mL, Desmopressin Acetate Nasal Spray 10 mcg/0.1mL, and STIMATE® Nasal Spray 1.5 mg/mL listed in the table below to the consumer level. These products are being recalled due to superpotency or amounts of desmopressin higher than specified." }, "verifiedAt": "2026-08-02" }, { "question": "Is desmopressin on FDA's 503A bulks list?", "answer": "No — desmopressin appears nowhere in FDA's list of bulk drug substances nominated for use in compounding under section 503A, updated 14 May 2026. It is in none of the three categories, verified by fetching and text-extracting the document on 2 August 2026: zero hits. That absence means something quite different from the absence of BPC-157 or MOTS-c, and reading it the same way would be a mistake. The 503A nomination list exists for bulk drug substances that are neither the subject of a USP monograph nor a component of an FDA-approved drug product. Desmopressin acetate is a component of many approved drug products, so it was never on that track — the same reason bremelanotide is absent. Being absent from the nomination list is therefore neither a permission nor a safety finding here; it is a statement that this substance was never part of that proceeding.", "source": { "url": "https://www.fda.gov/media/94155/download", "title": "Bulk Drug Substances Nominated for Use in Compounding Under Section 503A of the Federal Food, Drug, and Cosmetic Act", "publisher": "FDA", "date": "2026-05-14" }, "verifiedAt": "2026-08-02" }, { "question": "Is desmopressin the same thing as vasopressin?", "answer": "No. Desmopressin is a synthetic analogue of arginine vasopressin, not vasopressin itself, and FDA's approved labels describe every desmopressin product as 'a vasopressin analog' rather than as vasopressin. The distinction is carried through into what the products are approved for: the desmopressin labels are built around antidiuretic replacement in central diabetes insipidus, primary nocturnal enuresis, hemophilia A and von Willebrand's disease Type I. Note also that all FDA-approved desmopressin products contain the acetate salt, and that their labels state strengths in both desmopressin acetate and desmopressin base terms — NOCTIVA's label, for instance, describes a spray delivering desmopressin acetate 'equivalent to' a stated quantity of desmopressin. A number on a desmopressin product does not necessarily refer to the same thing as the same number on another.", "source": { "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2026/219873Orig1s000lbl.pdf", "title": "DESMODA (desmopressin acetate) oral solution — Highlights of Prescribing Information (NDA 219873)", "publisher": "FDA", "date": "2026-02-25", "quote": "DESMODA is a vasopressin analog indicated for the management of central diabetes insipidus as antidiuretic replacement therapy for adults and pediatric patients." }, "verifiedAt": "2026-08-02" } ] }, { "slug": "dulaglutide", "name": "Dulaglutide", "aliases": [ "Trulicity", "LY2189265" ], "url": "https://peptides101.com/compounds/dulaglutide", "moleculeNote": "Dulaglutide is a GLP-1 receptor agonist, but it is not a peptide and it is not a drug in the regulatory sense — it is a BIOLOGICAL PRODUCT. FDA's approved labeling describes the molecule as 'a fusion protein that consists of 2 identical, disulfide-linked chains, each containing an N-terminal GLP-1 analog sequence covalently linked to the Fc portion of a modified human immunoglobulin G4 (IgG4) heavy chain by a small peptide linker', with an overall molecular weight of approximately 63 kilodaltons, 'produced using mammalian cell (Chinese hamster ovary) culture'. Two consequences follow, and both are structural rather than rhetorical. It is licensed under section 351(a) of the Public Health Service Act rather than approved under section 505 of the FD&C Act, which places it outside the 503A compounding exemptions entirely. And it cannot be made by solid-phase peptide synthesis: a 63 kDa glycoprotein grown in CHO cell culture is not a molecule a research-chemical supplier can produce the way it produces a 15-residue peptide. That is the most likely reason dulaglutide is largely absent from the grey market that sells every other GLP-1.", "quickAnswer": "Dulaglutide is the active ingredient in Trulicity, a biological product licensed to Eli Lilly and Company under BLA 125469 and approved by FDA on 18 September 2014 under section 351(a) of the Public Health Service Act. The current FDA-approved labeling carries exactly two indications — improving glycemic control as an adjunct to diet and exercise in adults and pediatric patients 10 years of age and older with type 2 diabetes mellitus, and reducing the risk of major adverse cardiovascular events in adults with type 2 diabetes mellitus who have established cardiovascular disease or multiple cardiovascular risk factors — with no weight-management indication and a boxed warning for risk of thyroid C-cell tumors. Dulaglutide is also not a synthetic peptide: FDA's labeling describes a fusion protein of two identical disulfide-linked chains joining a GLP-1 analog sequence to the Fc portion of a modified human IgG4 heavy chain, of approximately 63 kilodaltons, produced using Chinese hamster ovary cell culture — and FDA has stated that biological products approved in a BLA under section 351 of the PHS Act 'are not eligible for the exemptions in section 503A of the FD&C Act' and 'will not be considered for the 503A bulks list', so dulaglutide sits outside the 503A compounding process rather than anywhere inside it.", "fdaStatus": { "value": "approved", "note": "FDA-approved, and the approval is a LICENSURE rather than a new drug approval: the letter refers to a Biologics License Application 'submitted under section 351(a) of the Public Health Service Act' and issues Trulicity under U.S. License No. 1891. Cross-checked against Drugs@FDA on 2026-08-02 via openFDA: application BLA125469, sponsor ELI LILLY AND CO, original submission approved 20140918 as a Type 1 New Molecular Entity, four TRULICITY products, every one with marketing status 'Prescription'. Read the quoted indication as the 2014 one, not the current one — it has been widened twice since, by the supplements recorded under fdaFindings, and the current verbatim indications are under fdaApproval below.", "source": { "url": "https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2014/125469Orig1s000ltr.pdf", "title": "BLA 125469 Approval Letter — Trulicity (dulaglutide)", "publisher": "FDA", "date": "2014-09-18", "quote": "We have approved your BLA for Trulicity (dulaglutide) effective this date. You are hereby authorized to introduce or deliver for introduction into interstate commerce, Trulicity, under your existing department of Health and Human Services U.S. License No. 1891. Trulicity is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus." }, "verifiedAt": "2026-08-02" }, "compoundingStatus": null, "evidence": { "tier": "proven-in-humans", "humanAdministrationChecked": true, "note": "Administration check RUN, not assumed. REWIND (NCT01394952) was opened and read on 2026-08-02: study type INTERVENTIONAL, phase 3, intervention type DRUG, name 'Dulaglutide' (other name LY2189265), description 'Administered subcutaneously', versus a subcutaneously administered placebo; randomised, double-masked, parallel assignment; enrolment 9,901 ACTUAL; lead sponsor Eli Lilly and Company; status COMPLETED with primary completion 2018-08-21 ACTUAL and results first posted 2019-10-08 ACTUAL. Dulaglutide was ADMINISTERED to humans — it was not measured as an endogenous biomarker, which is the trap that reduces MOTS-c and TB-500 from an apparent five human RCTs to an actual zero. Corroborated inside the regulatory record rather than only in the registry: FDA's own supplement approval letter names 'Study GBDJ (REWIND), a Phase 3 cardiovascular outcomes trial' as the basis for the cardiovascular indication, and section 14.5 of the approved labeling describes the same trial with the same registration number and the same enrolment. A second administration check was run on AWARD-PEDS (NCT02963766), the paediatric trial: INTERVENTIONAL, phase 3, intervention type DRUG 'Dulaglutide', 'Administered SC', 154 participants ACTUAL, Eli Lilly and Company, COMPLETED, results posted 2022-07-01. SCOPE — this tier attaches to the two approved indications and to the approved Trulicity products, and to nothing else. The REWIND result is a cardiovascular outcome in adults with type 2 diabetes who had established cardiovascular disease or multiple cardiovascular risk factors. It is not evidence for weight management, for use without type 2 diabetes, or for any product other than the licensed one.", "source": { "url": "https://clinicaltrials.gov/study/NCT01394952", "title": "REWIND — The Effect of Dulaglutide on Major Cardiovascular Events in Patients With Type 2 Diabetes", "publisher": "ClinicalTrials.gov", "date": "2018-08-21" }, "verifiedAt": "2026-08-02" }, "fdaApproval": { "applicationNumber": "BLA 125469 (U.S. License No. 1891)", "brandName": "Trulicity", "approvedIndication": "TRULICITY is indicated: As an adjunct to diet and exercise to improve glycemic control in adults and pediatric patients 10 years of age and older with type 2 diabetes mellitus. To reduce the risk of major adverse cardiovascular events (cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke) in adults with type 2 diabetes mellitus who have established cardiovascular disease or multiple cardiovascular risk factors.", "discontinued": false, "source": { "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2026/125469s065lbl.pdf", "title": "TRULICITY (dulaglutide) injection — Highlights of Prescribing Information", "publisher": "FDA", "date": "2026-03-12", "quote": "TRULICITY ® is indicated: • As an adjunct to diet and exercise to improve glycemic control in adults and pediatric patients 10 years of age and older with type 2 diabetes mellitus. • To reduce the risk of major adverse cardiovascular events (cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke) in adults with type 2 diabetes mellitus who have established cardiovascular disease or multiple cardiovascular risk factors." }, "verifiedAt": "2026-08-02" }, "fdaFindings": [ { "finding": "FDA has stated that biological products subject to approval in a biologics license application under section 351 of the Public Health Service Act are not eligible for the exemptions in section 503A of the FD&C Act, and will not be considered for the 503A bulks list. Dulaglutide is approved in such an application — BLA 125469, submitted under section 351(a) of the PHS Act.", "note": "The single most useful sentence on this record, and the reason this compound has no 503A status field at all. FDA is not saying dulaglutide was evaluated for compounding and rejected; it is saying molecules in its regulatory class are outside that process as a matter of eligibility. So the correct answer to 'what 503A category is dulaglutide in' is that the question does not apply — which is different from 'category 1', different from 'withdrawn', and different from the never-nominated silence that covers an approved small-molecule drug. SCOPE, because it is narrower than it looks: this quote is from FDA's 503A interim policy guidance and speaks to section 503A. FDA has made a materially similar statement about the 503B bulks list elsewhere; that document is not cited here and no 503B claim is made on this record. This is also not a statement that no lawful handling of the licensed product can occur — FDA has separate guidance on mixing, diluting or repackaging biological products outside the scope of an approved BLA, which this footnote itself cross-references.", "source": { "url": "https://www.fda.gov/media/174456/download", "title": "Interim Policy on Compounding Using Bulk Drug Substances Under Section 503A of the Federal Food, Drug, and Cosmetic Act — Guidance for Industry", "publisher": "FDA", "date": "2025-01-07", "quote": "Biological products subject to approval in a biologics license application (BLA) under section 351 of the Public Health Service Act (PHS Act) (42 U.S.C. 262) are not eligible for the exemptions in section 503A of the FD&C Act (21 U.S.C. 353a). Biological products subject to approval in a BLA under section 351 of the PHS Act will not be considered for the 503A bulks list." }, "verifiedAt": "2026-08-02" }, { "finding": "The FDA-approved labeling describes dulaglutide as a fusion protein of two identical, disulfide-linked chains, each containing an N-terminal GLP-1 analog sequence covalently linked to the Fc portion of a modified human immunoglobulin G4 heavy chain by a small peptide linker, with an overall molecular weight of approximately 63 kilodaltons, produced using mammalian cell (Chinese hamster ovary) culture.", "note": "Recorded verbatim because 'peptide' is doing the work in every list that groups this molecule with BPC-157 and semaglutide. FDA's own description is of an antibody-Fc fusion protein grown in cell culture, roughly twenty times the mass of semaglutide. The practical consequence is a manufacturing one and it explains an absence this site otherwise could not: a research-chemical supplier can synthesise a short peptide, and cannot culture a CHO cell line. Dulaglutide is correspondingly missing from FDA's warning letters about unapproved GLP-1 products, which name semaglutide, tirzepatide and retatrutide. We searched for and did not find any FDA warning letter naming dulaglutide as a research-labelled product; an absence found by searching is weaker than a document, and it is recorded here as an absence, not as a finding.", "source": { "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2026/125469s065lbl.pdf", "title": "TRULICITY (dulaglutide) injection — Highlights of Prescribing Information", "publisher": "FDA", "date": "2026-03-12", "quote": "Dulaglutide is a human GLP-1 receptor agonist. The molecule is a fusion protein that consists of 2 identical, disulfide-linked chains, each containing an N-terminal GLP-1 analog sequence covalently linked to the Fc portion of a modified human immunoglobulin G4 (IgG4) heavy chain by a small peptide linker and is produced using mammalian cell (Chinese hamster ovary) culture. … The overall molecular weight of dulaglutide is approximately 63 kilodaltons." }, "verifiedAt": "2026-08-02" }, { "finding": "Dulaglutide appears in none of Categories 1, 2 or 3 of FDA's list of bulk drug substances nominated for use in compounding under section 503A, updated 2026-05-14.", "note": "Verified by fetching the PDF with a browser user-agent and text-extracting it locally on 2026-08-02: zero occurrences of 'dulaglutide', and zero of 'glutide' in any form. This absence must NOT be read the way BPC-157's absence is read. BPC-157 was nominated, sat in Category 2, and left when the nominators withdrew. Dulaglutide was never in this document because, per the FDA guidance recorded above, a BLA biological product is not eligible for the 503A exemptions and will not be considered for this list. Absence here is neither permission, nor a safety finding, nor a withdrawal.", "source": { "url": "https://www.fda.gov/media/94155/download", "title": "Bulk Drug Substances Nominated for Use in Compounding Under Section 503A of the Federal Food, Drug, and Cosmetic Act", "publisher": "FDA", "date": "2026-05-14" }, "verifiedAt": "2026-08-02" }, { "finding": "FDA approved the cardiovascular indication on 2020-02-21, in a prior approval supplemental biologics license application, on the basis of Study GBDJ (REWIND).", "note": "Recorded because it ties the evidence tier on this record to a specific FDA action on a specific trial, rather than to a registry entry we found ourselves. FDA's letter also characterises this supplement as a 'FULFILLMENT OF POSTMARKETING REQUIREMENT' — the cardiovascular outcomes trial was an obligation attached to the original 2014 licensure, not a voluntary label expansion.", "source": { "url": "https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2020/125469Orig1s033ltr.pdf", "title": "BLA 125469/S-033 Supplement Approval — Trulicity (dulaglutide) injection", "publisher": "FDA", "date": "2020-02-21", "quote": "This Prior Approval supplemental biologics application provides for the addition of efficacy and safety information to the Prescribing Information, including a new indication for reduction of major adverse cardiovascular events in adults with type 2 diabetes mellitus, based on the clinical data from Study GBDJ (REWIND), a Phase 3 cardiovascular outcomes trial." }, "verifiedAt": "2026-08-02" }, { "finding": "FDA extended the glycemic-control indication to pediatric patients 10 years of age and older with type 2 diabetes mellitus on 2022-11-17, in a priority-reviewed prior approval supplemental biologics license application.", "note": "Note the precise scope: the paediatric extension reaches the GLYCEMIC indication only. The cardiovascular indication remains adults-only in the current labeling. Drugs@FDA records this supplement (SUPPL 51) with review priority PRIORITY, the only priority-reviewed submission in this application's history.", "source": { "url": "https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2022/125469Orig1s051ltr.pdf", "title": "BLA 125469/S-051 Supplement Approval — Trulicity (dulaglutide) injection", "publisher": "FDA", "date": "2022-11-17", "quote": "This Prior Approval sBLA provides for expansion of the indication for Trulicity, as an adjunct to diet and exercise to improve glycemic control, to pediatric patients 10 years of age and older with type 2 diabetes mellitus." }, "verifiedAt": "2026-08-02" }, { "finding": "Drugs@FDA lists four TRULICITY products under BLA 125469 — 0.75 mg/0.5 mL, 1.5 mg/0.5 mL, 3 mg/0.5 mL and 4.5 mg/0.5 mL injectable solutions, sponsor ELI LILLY AND CO — each with marketing status 'Prescription'. The most recent approved submission on the application is a labeling supplement approved 2026-03-12.", "note": "Recorded to answer a question the secondary corpus answers wrongly. Multiple widely syndicated pages state that Eli Lilly discontinued Trulicity in October 2024 and that it is no longer manufactured or distributed. FDA's own record does not support that as of 2026-08-02: no product on the application carries a discontinued marketing status, and FDA approved a labeling supplement to it in March 2026. What this finding does NOT establish is availability — Drugs@FDA marketing status is a regulatory field, not a supply report, and shortage status was not checked for this record. The strengths above are product identification, which is what is in the pen; this site does not publish what to do with it.", "source": { "url": "https://api.fda.gov/drug/drugsfda.json?search=products.active_ingredients.name:\"DULAGLUTIDE\"", "title": "Drugs@FDA record for BLA 125469 (openFDA drug/drugsfda endpoint)", "publisher": "FDA", "date": "2026-07-31" }, "verifiedAt": "2026-08-02" }, { "finding": "The Limitations of Use that appeared in Trulicity's labeling revised 11/2024 — including 'Not for treatment of type 1 diabetes mellitus' — do not appear anywhere in the labeling revised 03/2026. The approved indications are unchanged and remain confined to type 2 diabetes mellitus.", "note": "Recorded because the obvious misreading is available and wrong. Verified by text-extracting three labels locally on 2026-08-02: the string 'Limitations of Use' occurs twice in the 11/2024 label and zero times in the labels revised 05/2025 and 03/2026, so the section was dropped in the supplement approved 2025-05-28. The phrase 'type 1 diabetes' now occurs zero times in the current label. This is a change in what the labeling SAYS, not a change in what is approved: section 1 still reads 'type 2 diabetes mellitus' in both indications, so use in type 1 diabetes remains outside the approved indication. Note also that one former limitation survived as a warning rather than disappearing — the current section 5.6 still states that Trulicity 'is not recommended in patients with severe gastroparesis'. We did not identify FDA's stated reason for the removal and are not guessing at one.", "source": { "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/125469s061s062lbl.pdf", "title": "TRULICITY (dulaglutide) injection — Prescribing Information (revised 11/2024)", "publisher": "FDA", "date": "2024-11-04", "quote": "Limitations of Use: • Has not been studied in patients with a history of pancreatitis. Consider other antidiabetic therapies in these patients (1, 5.2). • Not for treatment of type 1 diabetes mellitus (1). • Not recommended in patients with severe gastrointestinal disease, including severe gastroparesis (1, 5.6)." }, "verifiedAt": "2026-08-02" } ], "safetySignals": [ { "signal": "Boxed warning — risk of thyroid C-cell tumors. In male and female rats, dulaglutide causes a dose-related and treatment-duration-dependent increase in the incidence of thyroid C-cell tumors (adenomas and carcinomas) after lifetime exposure. It is unknown whether TRULICITY causes thyroid C-cell tumors, including medullary thyroid carcinoma (MTC), in humans. TRULICITY is contraindicated in patients with a personal or family history of MTC and in patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2).", "note": "FDA's highest-level warning. The labeling also records human observations that the boxed warning itself does not carry: one case of MTC in a patient treated with Trulicity in a clinical trial, in a patient whose pretreatment calcitonin was approximately eight times the upper limit of normal, and an additional case of C-cell hyperplasia with elevated calcitonin following treatment in the cardiovascular outcomes trial. The labeling states that routine monitoring of serum calcitonin or thyroid ultrasound is of uncertain value for early detection of MTC in treated patients — so the contraindication is a screening question, and screening questions only get asked where there is a prescriber and a label to ask them.", "source": { "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2026/125469s065lbl.pdf", "title": "TRULICITY (dulaglutide) injection — Highlights of Prescribing Information", "publisher": "FDA", "date": "2026-03-12", "quote": "In male and female rats, dulaglutide causes a dose-related and treatment-duration-dependent increase in the incidence of thyroid C-cell tumors (adenomas and carcinomas) after lifetime exposure. It is unknown whether TRULICITY causes thyroid C-cell tumors, including medullary thyroid carcinoma (MTC), in humans as human relevance of dulaglutide-induced rodent thyroid C-cell tumors has not been determined." }, "verifiedAt": "2026-08-02" }, { "signal": "Labeled warnings and precautions include thyroid C-cell tumors, acute pancreatitis, hypoglycemia with concomitant use of insulin secretagogues or insulin, hypersensitivity reactions including anaphylactic reactions and angioedema, acute kidney injury due to volume depletion, severe gastrointestinal adverse reactions, diabetic retinopathy complications in patients with a history of diabetic retinopathy, acute gallbladder disease, and pulmonary aspiration during general anesthesia or deep sedation.", "note": "Reproduced in full because a nine-item warnings section is not what 'well tolerated' implies. The labeling gives the most common adverse reactions, at an incidence of 5 percent or greater, as nausea, diarrhea, vomiting, abdominal pain and decreased appetite. Postmarketing reports listed in the labeling additionally include hemorrhagic and necrotizing pancreatitis sometimes resulting in death, ileus, intestinal obstruction, cholecystitis, cholelithiasis requiring cholecystectomy, hepatitis, acute renal failure or worsening of chronic renal failure sometimes requiring hemodialysis, and alopecia — with FDA's standard caveat that voluntary reports from a population of uncertain size cannot establish frequency or causation.", "source": { "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2026/125469s065lbl.pdf", "title": "TRULICITY (dulaglutide) injection — Highlights of Prescribing Information", "publisher": "FDA", "date": "2026-03-12" }, "verifiedAt": "2026-08-02" }, { "signal": "Severe gastrointestinal adverse reactions were reported more frequently among patients receiving TRULICITY than placebo in the pool of placebo-controlled trials, and the labeling states that TRULICITY is not recommended in patients with severe gastroparesis. This section was revised in March 2026 and is flagged in the label's own Recent Major Changes.", "note": "The most recent substantive change to this label: the Recent Major Changes box reads 'Warnings and Precautions Severe Gastrointestinal Adverse Reactions (5.6) 03/2026'. QUOTE HANDLING: the labeling gives per-arm incidence figures paired with product strengths; those figures are elided with an ellipsis under this site's no-dosing policy. The finding — more frequent on drug than on placebo, and the gastroparesis recommendation — does not depend on them.", "source": { "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2026/125469s065lbl.pdf", "title": "TRULICITY (dulaglutide) injection — Highlights of Prescribing Information", "publisher": "FDA", "date": "2026-03-12", "quote": "Use of TRULICITY has been associated with gastrointestinal adverse reactions, sometimes severe … Severe gastrointestinal adverse reactions have also been reported postmarketing with GLP-1 receptor agonists. TRULICITY is not recommended in patients with severe gastroparesis." }, "verifiedAt": "2026-08-02" }, { "signal": "In a cardiovascular outcomes trial with median follow-up of 5.4 years, diabetic retinopathy complications were prospectively ascertained as a secondary composite endpoint and occurred slightly more often in the dulaglutide group than in the placebo group, with a larger proportion affected among patients who had a history of diabetic retinopathy at baseline.", "note": "Recorded because it runs the opposite way to the trial's headline. The same trial that produced the cardiovascular benefit produced a retinopathy signal, and the labeling carries both. The per-arm percentages in section 5.7 are stated alongside a product strength and are therefore not reproduced here; the direction of the difference and the history-of-retinopathy subgroup are the parts that matter. The labeling instructs monitoring of patients with a history of diabetic retinopathy.", "source": { "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2026/125469s065lbl.pdf", "title": "TRULICITY (dulaglutide) injection — Highlights of Prescribing Information", "publisher": "FDA", "date": "2026-03-12" }, "verifiedAt": "2026-08-02" }, { "signal": "In glycemic control trials in adults, 64 of 3,907 TRULICITY-treated patients (1.6%) developed anti-dulaglutide antibodies. Of those, 34 patients (0.9% of the overall population) developed dulaglutide-neutralizing antibodies and 36 patients (0.9%) developed antibodies against native GLP-1. The labeling states no clinically significant effect of anti-drug antibodies on pharmacokinetics, pharmacodynamics, safety or effectiveness was identified over the treatment durations studied.", "note": "Included because immunogenicity is a category of risk that exists for this molecule and does not exist in the same form for a synthetic peptide — it is what being a 63 kDa recombinant fusion protein costs. Read the label's own two qualifications: observed anti-drug antibody incidence is highly dependent on assay sensitivity and specificity, and differences in assay methods preclude comparison with other products. The most striking number is the smallest one — antibodies against NATIVE GLP-1, the body's own hormone, in 0.9% of treated patients. The labeling reports no identified clinical consequence; it does not report that there is none.", "source": { "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2026/125469s065lbl.pdf", "title": "TRULICITY (dulaglutide) injection — Highlights of Prescribing Information", "publisher": "FDA", "date": "2026-03-12" }, "verifiedAt": "2026-08-02" } ], "faqs": [ { "question": "Is Trulicity approved for weight loss?", "answer": "No. The FDA-approved labeling for Trulicity (dulaglutide, BLA 125469) carries two indications and no others: as an adjunct to diet and exercise to improve glycemic control in adults and pediatric patients 10 years of age and older with type 2 diabetes mellitus, and to reduce the risk of major adverse cardiovascular events (cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke) in adults with type 2 diabetes mellitus who have established cardiovascular disease or multiple cardiovascular risk factors. Weight management is not among them, and both indications are gated on type 2 diabetes mellitus, so there is no approved use of Trulicity in a patient who does not have type 2 diabetes. Prescribing it for weight loss is off-label use — a decision for a licensed prescriber, and not one this labeling supports. Weight change is reported in the labeling as a trial outcome in the type 2 diabetes studies; a reported outcome in a trial is not an approved indication.", "source": { "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2026/125469s065lbl.pdf", "title": "TRULICITY (dulaglutide) injection — Highlights of Prescribing Information", "publisher": "FDA", "date": "2026-03-12", "quote": "TRULICITY ® is indicated: • As an adjunct to diet and exercise to improve glycemic control in adults and pediatric patients 10 years of age and older with type 2 diabetes mellitus. • To reduce the risk of major adverse cardiovascular events (cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke) in adults with type 2 diabetes mellitus who have established cardiovascular disease or multiple cardiovascular risk factors." }, "verifiedAt": "2026-08-02" }, { "question": "Is dulaglutide a peptide?", "answer": "Not in the sense the peptide market uses the word. FDA's approved labeling describes dulaglutide as 'a fusion protein that consists of 2 identical, disulfide-linked chains, each containing an N-terminal GLP-1 analog sequence covalently linked to the Fc portion of a modified human immunoglobulin G4 (IgG4) heavy chain by a small peptide linker', with an overall molecular weight of approximately 63 kilodaltons, 'produced using mammalian cell (Chinese hamster ovary) culture'. So there is a GLP-1 peptide sequence inside the molecule, but the molecule itself is an antibody-fragment fusion protein roughly twenty times the mass of semaglutide, and it is grown in cultured cells rather than chemically synthesised. That is why dulaglutide is licensed as a biological product under section 351(a) of the Public Health Service Act instead of approved as a drug, and it is the most likely reason dulaglutide does not appear in the research-chemical GLP-1 market: a supplier that can synthesise a short peptide cannot culture a CHO cell line.", "source": { "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2026/125469s065lbl.pdf", "title": "TRULICITY (dulaglutide) injection — Highlights of Prescribing Information", "publisher": "FDA", "date": "2026-03-12", "quote": "Dulaglutide is a human GLP-1 receptor agonist. The molecule is a fusion protein that consists of 2 identical, disulfide-linked chains, each containing an N-terminal GLP-1 analog sequence covalently linked to the Fc portion of a modified human immunoglobulin G4 (IgG4) heavy chain by a small peptide linker and is produced using mammalian cell (Chinese hamster ovary) culture. … The overall molecular weight of dulaglutide is approximately 63 kilodaltons." }, "verifiedAt": "2026-08-02" }, { "question": "Can dulaglutide be compounded the way semaglutide and tirzepatide were?", "answer": "No, and the reason is categorical rather than case-by-case. Dulaglutide is approved in a biologics license application — BLA 125469, submitted under section 351(a) of the Public Health Service Act — and FDA has stated that 'Biological products subject to approval in a biologics license application (BLA) under section 351 of the Public Health Service Act (PHS Act) (42 U.S.C. 262) are not eligible for the exemptions in section 503A of the FD&C Act (21 U.S.C. 353a). Biological products subject to approval in a BLA under section 351 of the PHS Act will not be considered for the 503A bulks list.' Dulaglutide accordingly appears in none of Categories 1, 2 or 3 of FDA's 503A bulk drug substances list updated 14 May 2026 — verified by reading the document, where the word does not occur at all. Read the scope precisely: that quotation is from FDA's section 503A guidance and speaks to section 503A. It is not a statement about every possible handling of the licensed product, and FDA has separate guidance covering pharmacies and outsourcing facilities that mix, dilute or repackage biological products outside the scope of an approved BLA.", "source": { "url": "https://www.fda.gov/media/174456/download", "title": "Interim Policy on Compounding Using Bulk Drug Substances Under Section 503A of the Federal Food, Drug, and Cosmetic Act — Guidance for Industry", "publisher": "FDA", "date": "2025-01-07", "quote": "Biological products subject to approval in a biologics license application (BLA) under section 351 of the Public Health Service Act (PHS Act) (42 U.S.C. 262) are not eligible for the exemptions in section 503A of the FD&C Act (21 U.S.C. 353a). Biological products subject to approval in a BLA under section 351 of the PHS Act will not be considered for the 503A bulks list." }, "verifiedAt": "2026-08-02" }, { "question": "Has Trulicity been discontinued?", "answer": "Not according to FDA's own record as of 2 August 2026. Drugs@FDA lists four TRULICITY products under BLA 125469, sponsor ELI LILLY AND CO, and every one of them carries marketing status 'Prescription' — none is listed as discontinued. FDA also approved a labeling supplement to the same application on 12 March 2026, and the resulting prescribing information is the current approved labeling. Web pages stating that Eli Lilly discontinued Trulicity in October 2024 and that it is no longer manufactured or distributed are contradicted by that record. One caution on what this does and does not answer: marketing status in Drugs@FDA is a regulatory field, not a supply report, so it does not establish that a given presentation is available at a given pharmacy. This record did not verify shortage status, and does not claim anything about it.", "source": { "url": "https://api.fda.gov/drug/drugsfda.json?search=products.active_ingredients.name:\"DULAGLUTIDE\"", "title": "Drugs@FDA record for BLA 125469 (openFDA drug/drugsfda endpoint)", "publisher": "FDA", "date": "2026-07-31" }, "verifiedAt": "2026-08-02" }, { "question": "Did a clinical trial show dulaglutide reduces cardiovascular events?", "answer": "Yes, in one specific population, and FDA approved an indication on that basis. REWIND (NCT01394952) was a multi-national, randomised, placebo-controlled, double-blind phase 3 trial in which 9,901 adults with type 2 diabetes mellitus and either established cardiovascular disease or multiple cardiovascular risk factors were randomised to dulaglutide or placebo, both added to standard of care, with a median follow-up of 5.4 years. In that trial, the risk of first occurrence of the primary composite endpoint of cardiovascular death, non-fatal myocardial infarction or non-fatal stroke was significantly reduced (hazard ratio 0.88, 95% CI 0.79 to 0.99), and FDA's supplement approval letter of 21 February 2020 records that the cardiovascular indication was added 'based on the clinical data from Study GBDJ (REWIND), a Phase 3 cardiovascular outcomes trial'. Two limits are worth reading with it. The result belongs to that enrolled population — adults with type 2 diabetes at cardiovascular risk — and the approved indication is written to match it. And the same trial prospectively ascertained diabetic retinopathy complications as a secondary endpoint and found them slightly more common on dulaglutide than on placebo, which is why the approved labeling carries both the cardiovascular indication and a diabetic retinopathy warning.", "source": { "url": "https://clinicaltrials.gov/study/NCT01394952", "title": "REWIND — The Effect of Dulaglutide on Major Cardiovascular Events in Patients With Type 2 Diabetes", "publisher": "ClinicalTrials.gov", "date": "2018-08-21", "quote": "This Prior Approval supplemental biologics application provides for the addition of efficacy and safety information to the Prescribing Information, including a new indication for reduction of major adverse cardiovascular events in adults with type 2 diabetes mellitus, based on the clinical data from Study GBDJ (REWIND), a Phase 3 cardiovascular outcomes trial." }, "verifiedAt": "2026-08-02" }, { "question": "Is dulaglutide approved for children?", "answer": "Partly, and the boundary matters. FDA extended one of Trulicity's two indications to children on 17 November 2022: the supplement approval letter states that it 'provides for expansion of the indication for Trulicity, as an adjunct to diet and exercise to improve glycemic control, to pediatric patients 10 years of age and older with type 2 diabetes mellitus.' Only the glycemic-control indication was extended — the cardiovascular indication in the current labeling remains confined to adults, and there is no approved paediatric use for weight management or for type 1 diabetes. Nothing in the extension softens the labeled risks: the boxed warning for risk of thyroid C-cell tumors, and the contraindications in personal or family history of medullary thyroid carcinoma and in Multiple Endocrine Neoplasia syndrome type 2, are not age-limited.", "source": { "url": "https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2022/125469Orig1s051ltr.pdf", "title": "BLA 125469/S-051 Supplement Approval — Trulicity (dulaglutide) injection", "publisher": "FDA", "date": "2022-11-17", "quote": "This Prior Approval sBLA provides for expansion of the indication for Trulicity, as an adjunct to diet and exercise to improve glycemic control, to pediatric patients 10 years of age and older with type 2 diabetes mellitus." }, "verifiedAt": "2026-08-02" } ] }, { "slug": "elamipretide", "name": "Elamipretide", "aliases": [ "SS-31", "MTP-131", "Bendavia", "Forzinity", "elamipretide hydrochloride" ], "url": "https://peptides101.com/compounds/elamipretide", "moleculeNote": "A four-residue mitochondria-targeting peptide. The FDA-approved labeling describes the molecule precisely: 'All amino acid residues in FORZINITY have the L configuration except for arginine which has the D configuration. The peptide sequence is denoted as D-Arg-2,6-dimethyl-Tyr-Lys-Phe-NH2.' The approved product contains the HYDROCHLORIDE salt — Drugs@FDA lists the active ingredient as ELAMIPRETIDE HYDROCHLORIDE under NDA 215244, and the label gives the chemical name as 'L-Phenylalaninamide, D-arginyl-2,6-dimethyl-L-tyrosyl-L-lysyl-, hydrochloride (1:3)'. THE NAMING IS THE PROBLEM HERE. The same molecule travels under at least four names: elamipretide (INN), SS-31 (the Szeto-Schiller research designation used throughout the literature), MTP-131 and Bendavia (the sponsor's earlier development codes, both of which appear in Stealth's own trial registrations and in FDA's review tables), and FORZINITY (the approved brand). A reader searching 'SS-31' and a regulator searching 'elamipretide' are looking at one substance, and the mismatch is a large part of why material sold as SS-31 is discussed as though no FDA record existed. It does — see below.", "quickAnswer": "Elamipretide is FDA-approved, under the brand name FORZINITY (NDA 215244, Stealth BioTherapeutics), but only under accelerated approval granted 19 September 2025 and only for one indication: 'to improve muscle strength in adult and pediatric patients with Barth syndrome weighing at least 30 kg.' The FDA-approved labeling states that in the randomized, double-blind, placebo-controlled trial 'FORZINITY was not superior to placebo on these primary endpoints', and that increases in knee extensor muscle strength 'were not observed during the randomized trial but were observed during the extension period' — the uncontrolled, open-label extension. FDA's own clinical and biostatistical reviewers and Cross-Discipline Team Leader concluded there was 'not substantial evidence of effectiveness on knee muscle strength for accelerated approval' and recommended a Complete Response; the signatory authority overruled them, writing that the decision accepts 'more uncertainty than we would accept for more common diseases' in a disease affecting roughly 150 patients in the United States with no approved treatments. FDA required a randomized, double-blind, placebo-controlled confirmatory trial and stated that if it 'fails to verify clinical benefit or is not conducted with due diligence … we may withdraw this approval.' No FDA approval covers elamipretide, or the same molecule sold as SS-31, for mitochondrial myopathy, heart failure, macular degeneration, athletic performance or anti-aging use.", "fdaStatus": { "value": "approved", "note": "FDA-approved, and the qualifier in front of the word is doing all the work: this is an ACCELERATED approval under section 506(c) and 21 CFR 314.510, for ONE indication, in ONE ultra-rare genetic disease, on an intermediate clinical endpoint. Cross-checked against Drugs@FDA via the openFDA `drug/drugsfda` endpoint on 2026-08-02: NDA 215244, sponsor STEALTH BIOTHERAPS, ORIG-1 submission status AP dated 20250919, review priority PRIORITY, submission class Type 1 New Molecular Entity, orphan property, one product — FORZINITY, solution, subcutaneous, marketing status Prescription. Both `openfda.generic_name` and `products.active_ingredients.name` return the same single application, so this is not an artifact of one query field. This status does NOT travel. It attaches to the approved product, at the approved indication, in the approved population. It says nothing about material sold as SS-31, and nothing about the uses — mitochondrial myopathy, heart failure, macular degeneration, anti-aging — for which no approval exists.", "source": { "url": "https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2025/215244Orig1s000ltr.pdf", "title": "NDA 215244 — ACCELERATED APPROVAL letter, Forzinity (elamipretide) injection", "publisher": "FDA", "date": "2025-09-19", "quote": "This NDA provides for the use of Forzinity (elamipretide) injection to improve muscle strength in adult and pediatric patients with Barth syndrome weighing at least 30 kg. … We have completed our review of this application, as amended. It is approved under accelerated approval pursuant to section 506(c) of the Federal Food, Drug, and Cosmetic Act (FDCA) and 21 CFR 314.510, effective on the date of this letter, for use as recommended in the enclosed agreed-upon labeling." }, "verifiedAt": "2026-08-02" }, "compoundingStatus": null, "evidence": { "tier": "promising-but-unproven", "humanAdministrationChecked": true, "note": "ADMINISTRATION CHECK RUN, NOT ASSUMED. TAZPOWER (NCT03098797) was opened and read on 2026-08-02: intervention type DRUG, elamipretide given by subcutaneous injection versus placebo, randomized crossover, quadruple-masked, enrolment 12 ACTUAL, lead sponsor Stealth BioTherapeutics Inc., status COMPLETED, results first posted 2024-04-16. Elamipretide was ADMINISTERED to human participants — this is not the endogenous-biomarker trap that reduces MOTS-c and TB-500 from an apparent five human RCTs to an actual zero. SO WHY IS AN FDA-APPROVED DRUG NOT 'proven-in-humans'? Because that tier means efficacy established by adequate, well-controlled human trials, and the documents will not carry it. Read the label's own section 14, quoted above: the randomized, placebo-controlled trial MISSED BOTH PRIMARY ENDPOINTS, and the muscle-strength increases that the approval rests on were NOT seen during that trial — they appeared in the uncontrolled, open-label, single-arm extension in which every participant knew they were receiving drug. FDA's own clinical reviewers, biostatistical reviewers and Cross-Discipline Team Leader concluded there was not substantial evidence of effectiveness and recommended a Complete Response; the signatory authority overruled them on the basis of disease rarity and unmet need, and wrote that the conclusion 'accepts more uncertainty than we would for less rare diseases'. Both of those positions are recorded verbatim, with their own sources, under fdaFindings. The confirmatory randomized trial FDA required (NCT07531251) only began enrolling on 2026-07-02, with estimated primary completion 2029-09-30. This tier is therefore not a criticism of the approval decision — accelerated approval is designed to permit exactly this trade — it is an accurate statement of where the evidence stands. 'Approved' and 'proven' are different claims, and elamipretide is the clearest case on this site where they diverge. Scope: this tier attaches to Barth syndrome, the only indication studied to approval. For primary mitochondrial myopathy the Phase 3 programme was terminated for missing its primary endpoints, and for dry age-related macular degeneration a Phase 3 (NCT06373731) is still running with no result.", "source": { "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/215244s000lbl.pdf", "title": "FORZINITY (elamipretide) injection, for subcutaneous use — Prescribing Information", "publisher": "FDA", "date": "2025-09-19", "quote": "FORZINITY was evaluated in a randomized, double-blind, placebo-controlled, crossover trial and its 192-week, open-label, single-arm extension period. The randomized trial evaluated the efficacy and safety of once daily FORZINITY … in 12 subjects ≥12-years-old and >30 kg with genetically confirmed Barth syndrome. The primary endpoints for the randomized trial were distance walked during 6-minute walk test and Total Fatigue Score on the Barth syndrome Symptom Assessment. FORZINITY was not superior to placebo on these primary endpoints. … Increases in knee extensor muscle strength were not observed during the randomized trial but were observed during the extension period." }, "verifiedAt": "2026-08-02" }, "fdaApproval": { "applicationNumber": "NDA 215244", "brandName": "FORZINITY", "approvedIndication": "FORZINITY is indicated to improve muscle strength in adult and pediatric patients with Barth syndrome weighing at least 30 kg. This indication is approved under accelerated approval based on an improvement in knee extensor muscle strength, an intermediate clinical endpoint [see Clinical Studies (14)]. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.", "discontinued": false, "source": { "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/215244s000lbl.pdf", "title": "FORZINITY (elamipretide) injection, for subcutaneous use — Prescribing Information", "publisher": "FDA", "date": "2025-09-19" }, "verifiedAt": "2026-08-02" }, "fdaFindings": [ { "finding": "FDA has recorded that the clinical and biostatistical reviewers and the Cross-Discipline Team Leader on this application concluded there is not substantial evidence of effectiveness on knee muscle strength for accelerated approval, and recommended a Complete Response action. Their conclusion was overruled by the signatory authority.", "note": "The single most load-bearing document on this record, and it is FDA disagreeing with itself in public. This is not an outside critic and not a short-seller note — it is the Integrated Review of the approved application, stating that the review team recommended rejection. The review also records the team's conclusion in statutory terms: that SPIBA-201, Part 1 'is an adequate and well-controlled trial that did not demonstrate a treatment effect', that Part 2 'is not an adequate and well-controlled trial', and hence that 'this NDA does not meet the statutory requirement of substantial evidence of effectiveness, even in the context of a rare disease'. What this finding is NOT: it is not evidence that the approval was improper. Accelerated approval exists precisely so that a signatory authority can accept more uncertainty for a serious disease with no treatment, and the reasoning for doing so is recorded here too and quoted in the next finding. Both halves belong on the page. A record that carried only the dissent would be as misleading as the vendor pages that carry only the word 'FDA-approved'.", "source": { "url": "https://www.accessdata.fda.gov/drugsatfda_docs/nda/2025/215244Orig1s000IntegratedR.pdf", "title": "NDA 215244Orig1s000 — Integrated Review (NDA Re-submission Review), Forzinity (elamipretide)", "publisher": "FDA", "date": "2025-10-02", "quote": "The clinical and biostatistical reviewers and the Cross-Discipline Team Leader (CDTL) conclude that there is not substantial evidence of effectiveness on knee muscle strength for accelerated approval and recommend a Complete Response action. They note several limitations of the knee muscle strength data, including, but not limited to, the open-label design of SPIBA-201, Part 2, the lack of a control arm, and the potential impact of known and unknown sources of bias (e.g., subject attrition, effort-dependence)." }, "verifiedAt": "2026-08-02" }, { "finding": "FDA has stated that its conclusion of an effect on knee extensor muscle strength accepts more uncertainty than it would accept for less rare or common diseases, and that the signatory authority concluded this greater uncertainty is acceptable in the context of a disease affecting approximately 150 patients in the United States with no approved treatments.", "note": "The other half of the decision, in FDA's words, and the reason this record does not read as an accusation. FDA is not claiming certainty and then hiding the doubt — it wrote the doubt into the approval document. The reasoning is explicitly rarity-scaled: the same evidence in a common disease would not have been accepted. That is precisely why the approval cannot be lifted out of Barth syndrome and used as a general endorsement of the molecule, which is the move the consumer market makes with it.", "source": { "url": "https://www.accessdata.fda.gov/drugsatfda_docs/nda/2025/215244Orig1s000IntegratedR.pdf", "title": "NDA 215244Orig1s000 — Integrated Review (NDA Re-submission Review), Forzinity (elamipretide)", "publisher": "FDA", "date": "2025-10-02", "quote": "The signatory authority agrees that there is more uncertainty than we would accept for more common diseases, but concludes that we should accept the extent of uncertainty in the data in the context of this very rare (~150 subjects in the United States), serious disease with no approved treatments … The signatory authority concludes this greater uncertainty is acceptable in this context, when balanced against the risk of rejecting or delaying the marketing of an effective therapy." }, "verifiedAt": "2026-08-02" }, { "finding": "FDA has stated that the observed muscle strength measurement involves only a single muscle group and is not accompanied by substantial evidence demonstrating an effect of elamipretide on an appropriate functional measure or on any endpoint directly measuring clinical benefit.", "note": "This is the sentence that defines what the approval does and does not assert. An intermediate clinical endpoint is, by definition, not clinical benefit — it is a measure 'reasonably likely to predict' it, and the prediction is the thing the confirmatory trial exists to test. FDA's benefit-risk table says the same thing in the other direction: 'we cannot conclude at the present time that the observed increases in muscle strength in a single muscle group assessed using HHD provides clinical benefit.' Anyone reading 'FDA-approved to improve muscle strength' as 'FDA found it makes patients function better' is reading past a sentence FDA wrote to prevent exactly that.", "source": { "url": "https://www.accessdata.fda.gov/drugsatfda_docs/nda/2025/215244Orig1s000IntegratedR.pdf", "title": "NDA 215244Orig1s000 — Integrated Review (NDA Re-submission Review), Forzinity (elamipretide)", "publisher": "FDA", "date": "2025-10-02", "quote": "The observed muscle strength measurement by HHD involves only a single muscle group (knee extensor muscles) and is not accompanied by substantial evidence demonstrating an effect of elamipretide on an appropriate functional measure or on any endpoints directly measuring clinical benefit." }, "verifiedAt": "2026-08-02" }, { "finding": "FDA has stated that the randomized, double-blind, placebo-controlled crossover trial did not show superiority of elamipretide to placebo on either component of its primary endpoint family — distance walked on the 6-minute walk test (p=0.97) and total fatigue score on the Barth syndrome symptom assessment (p=0.89) — and that none of the secondary endpoints achieved even nominal statistical significance (p=0.21-1.00).", "note": "The controlled evidence, stated by FDA with the p-values attached. p=0.97 and p=0.89 are not near-misses; they are the numbers you get when nothing separated. FDA's benefit-risk table restates it flatly: 'Elamipretide was not superior to placebo on any of these endpoints' in Part 1, across the 6-minute walk test, fatigue, knee extensor strength, 5-times sit-to-stand, Sway balance, echocardiographic parameters and MLCL:CL ratios. The label carries the same finding in plainer words — 'FORZINITY was not superior to placebo on these primary endpoints' — which is why it is quoted against the label under `evidence` and against the review here. Two documents, one finding, no reliance on either alone.", "source": { "url": "https://www.accessdata.fda.gov/drugsatfda_docs/nda/2025/215244Orig1s000IntegratedR.pdf", "title": "NDA 215244Orig1s000 — Integrated Review (NDA Re-submission Review), Forzinity (elamipretide)", "publisher": "FDA", "date": "2025-10-02", "quote": "SPIBA-201, Part 1 did not show superiority of elamipretide to placebo at the end of 12 weeks of treatment on the primary endpoint family of distance walked on 6-minute walk test (6MWT) (p=0.97) and total fatigue score (TFS) on the Barth syndrome symptom assessment (BTHA-SA) (p=0.89). While no alpha remained to test secondary endpoints, it is notable that none of the secondary endpoints achieved even nominal statistical significance (p=0.21-1.00)." }, "verifiedAt": "2026-08-02" }, { "finding": "FDA has stated that elamipretide does not directly target the underlying genetic defect that causes Barth syndrome, nor does it meaningfully impact the elevated cardiolipin ratio, the direct sequelae of the mutation in the Tafazzin gene.", "note": "Recorded because the mechanism story is what the consumer market actually sells. Elamipretide is marketed as a cardiolipin-targeting mitochondrial repair peptide, and the FDA-approved label does describe it as 'a mitochondrial cardiolipin binder that localizes to the inner mitochondrial membrane'. But in the one human disease where the cardiolipin defect is the whole pathology, FDA's reviewers recorded that the drug did not meaningfully move the cardiolipin ratio. A binding mechanism that is real at the membrane is not the same as a measured effect on the biochemistry, and neither is the same as clinical benefit. Attribution note: this sentence states the review team's position, and the signatory authority took a different view of the same nonclinical data, concluding that reliance on it as confirmatory evidence 'in this very rare disease and narrowly defined context is reasonable'.", "source": { "url": "https://www.accessdata.fda.gov/drugsatfda_docs/nda/2025/215244Orig1s000IntegratedR.pdf", "title": "NDA 215244Orig1s000 — Integrated Review (NDA Re-submission Review), Forzinity (elamipretide)", "publisher": "FDA", "date": "2025-10-02", "quote": "They also note that while there is some nonclinical mechanistic data, elamipretide does not directly target the underlying genetic defect that causes BTHS, nor does it meaningfully impact the elevated cardiolipin ratio, the direct sequelae of the mutation in the Tafazzin gene." }, "verifiedAt": "2026-08-02" }, { "finding": "FDA required a randomized, double-blind, placebo-controlled confirmatory trial in patients 5 years and older with Barth syndrome to verify and describe the clinical benefit predicted by improvements in knee extensor muscle strength, and stated that if the required postmarketing clinical trial fails to verify clinical benefit or is not conducted with due diligence, it may withdraw this approval.", "note": "The approval is conditional and FDA says so in the approval letter itself. The agreed timetable in the letter runs: study initiation 03/2026, full enrolment 03/2028, study completion 09/2029, final report 03/2030. That is the earliest date on which anyone will know whether the muscle-strength finding predicts clinical benefit. Three further postmarketing requirements sit alongside it under section 505(o), and they are worth naming because they describe what is NOT yet known about long-term exposure: 4802-2, a 26-week carcinogenicity study in TgRasH2 mice; 4802-3, a 2-year carcinogenicity study in rats, final report due 01/2030; and 4802-4, a clinical pharmacokinetic study of the effect of Forzinity on metformin, a sensitive MATE1 substrate. FDA imposed the carcinogenicity studies having determined that spontaneous adverse-event reporting 'will not be sufficient to identify an unexpected serious risk of carcinogenicity and drug-drug interactions'. Carcinogenicity is an open question with a 2030 answer date.", "source": { "url": "https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2025/215244Orig1s000ltr.pdf", "title": "NDA 215244 — ACCELERATED APPROVAL letter, Forzinity (elamipretide) injection", "publisher": "FDA", "date": "2025-09-19", "quote": "Pursuant to section 506(c) of the FDCA and 21 CFR 314.510 you are required to conduct an adequate and well-controlled clinical trial intended to verify and describe clinical benefit. You are required to conduct this clinical trial with due diligence. If your required postmarketing clinical trial fails to verify clinical benefit or is not conducted with due diligence, including with respect to the conditions set forth below, we may withdraw this approval. … 4802-1 Conduct a randomized, double-blind, placebo-controlled trial in patients 5 years and older with Barth syndrome to verify and describe the clinical benefit of Forzinity predicted by improvements in knee extensor muscle strength assessed by handheld dynamometry" }, "verifiedAt": "2026-08-02" }, { "finding": "FDA granted accelerated approval even though the required post-approval confirmatory trial was not underway at the time of approval, stating it had sufficient assurances from the applicant that the trial would be conducted diligently and in a timely manner.", "note": "Recorded because the timeline is the part everyone skips. The approval issued 2025-09-19 with no confirmatory trial running. The confirmatory trial — SPIBA-401, registered as NCT07531251, a Phase 3b/4 randomized, double-blind, placebo-controlled, parallel-group trial in genetically confirmed Barth syndrome — posted its first registration 2026-04-15 and records an actual start date of 2026-07-02, with estimated primary completion 2029-09-30. As of 2026-08-02 it is RECRUITING with an estimated enrolment of 48. Its own registered summary states the objective in the sponsor's words: 'The primary trial objective is to confirm the efficacy of elamipretide which is approved in the United States (FORZINITY™) under the accelerated approval based on an improvement in knee extensor muscle strength, an intermediate clinical endpoint.' The confirmation is pending, by the sponsor's own description.", "source": { "url": "https://www.accessdata.fda.gov/drugsatfda_docs/nda/2025/215244Orig1s000IntegratedR.pdf", "title": "NDA 215244Orig1s000 — Integrated Review (NDA Re-submission Review), Forzinity (elamipretide)", "publisher": "FDA", "date": "2025-10-02", "quote": "we have sufficient assurances from the Applicant that they will conduct the trial in a diligent and timely manner and have concluded that granting accelerated approval of elamipretide is appropriate at this time even though the post-approval confirmatory trial is not underway." }, "verifiedAt": "2026-08-02" }, { "finding": "FDA issued a Complete Response letter on this application on 15 May 2025, before the resubmission that led to approval.", "note": "The regulatory history in one line, from the approval letter. FDA's Integrated Review adds what the Complete Response was about: FDA declined to approve on the endpoints originally proposed, the Signatory Authority identified knee extensor muscle strength as a possible intermediate clinical endpoint, and the letter also 'noted deficiencies at the drug product manufacturing facility that would need to be resolved before this application could be approved'. On resubmission the Office of Pharmaceutical Quality confirmed the facility deficiencies were resolved. SOURCING CAUTION: the Integrated Review's narrative sentence about this letter contains an evident typographical error in the year. The date used here is taken from the approval letter, which is unambiguous.", "source": { "url": "https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2025/215244Orig1s000ltr.pdf", "title": "NDA 215244 — ACCELERATED APPROVAL letter, Forzinity (elamipretide) injection", "publisher": "FDA", "date": "2025-09-19", "quote": "Please refer to your new drug application (NDA) dated January 29, 2024, received January 29, 2024, and your amendments, submitted under section 505(b) of the Federal Food, Drug, and Cosmetic Act (FDCA) for Forzinity (elamipretide) injection. We acknowledge receipt of your amendment dated August 15, 2025, which constituted a complete response to our May 15, 2025, action letter." }, "verifiedAt": "2026-08-02" }, { "finding": "Elamipretide appears in none of Categories 1, 2 or 3 of the 503A bulk drug substances list updated 2026-05-14.", "note": "Recorded to close a misreading, not to assert a status — which is why this record carries no compoundingStatus at all. Verified by fetching the document with a browser user-agent and text-extracting it locally on 2026-08-02: zero hits for 'elamipretide', and zero for 'SS-31', 'MTP-131' and 'Bendavia'. This absence means something different from BPC-157's absence. BPC-157 was nominated and left Category 2 when its nominators withdrew. Elamipretide was never in the 503A nomination system at all — that route is for substances WITHOUT an approved product, and elamipretide has one. Categorical silence here is neither permission nor a safety finding, and it is emphatically not a route by which material sold as SS-31 becomes compoundable.", "source": { "url": "https://www.fda.gov/media/94155/download", "title": "Bulk Drug Substances Nominated for Use in Compounding Under Section 503A of the Federal Food, Drug, and Cosmetic Act", "publisher": "FDA", "date": "2026-05-14" }, "verifiedAt": "2026-08-02" } ], "safetySignals": [ { "signal": "The FDA-approved labeling warns of the risk of benzyl alcohol toxicity in neonates. FORZINITY contains benzyl alcohol as a preservative and is not approved for use in neonates. Serious adverse reactions, including fatal reactions, of new onset or worsening metabolic acidosis that progressed to neurotoxicity, and in some cases gasping syndrome, have been reported in low-birth weight and preterm neonates who received benzyl alcohol-containing drugs intravenously.", "note": "The only Warnings and Precautions entry in the Highlights, and it is about an EXCIPIENT rather than the peptide. Worth reading precisely for that reason: what is in the vial alongside the active ingredient carries its own labeled risk, and FDA states the minimum quantity at which these reactions occur is not known. There is no boxed warning on this label.", "source": { "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/215244s000lbl.pdf", "title": "FORZINITY (elamipretide) injection, for subcutaneous use — Prescribing Information", "publisher": "FDA", "date": "2025-09-19", "quote": "FORZINITY is not approved for use in neonates. Serious adverse reactions, including fatal reactions, of new onset or worsening metabolic acidosis that progressed to neurotoxicity, and in some cases gasping syndrome, have been reported in low-birth weight neonates (less than 2,500 grams) and preterm neonates (gestational age less than 34 weeks) who received benzyl alcohol (BA)-containing drugs intravenously. … The minimum amount of BA at which these serious adverse reactions, including fatal reactions, may occur is not known." }, "verifiedAt": "2026-08-02" }, { "signal": "The FDA-approved labeling warns of hypersensitivity reactions, including serious allergic reactions requiring emergency medical intervention, reported in patients receiving FORZINITY. Serious hypersensitivity to elamipretide or any excipient is a contraindication.", "note": "Note the window FDA specifies: 'within minutes to months after treatment initiation'. A tolerated first injection is not evidence of a tolerated course. The label directs that if a serious hypersensitivity reaction occurs the drug is stopped and emergency treatment instituted 'including epinephrine, antihistamines, and corticosteroids as clinically indicated', and that such patients 'should not be rechallenged'. This is a monitoring instruction to a prescriber, and it is the kind of instruction that does not exist at all for an unapproved vial bought under a research label.", "source": { "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/215244s000lbl.pdf", "title": "FORZINITY (elamipretide) injection, for subcutaneous use — Prescribing Information", "publisher": "FDA", "date": "2025-09-19", "quote": "Hypersensitivity reactions, including serious allergic reactions requiring emergency medical intervention, have been reported in patients receiving FORZINITY. These reactions have included skin manifestations such as rash, papular lesions, and eczematous dermatitis, as well as respiratory symptoms including cough … Reactions may occur within minutes to months after treatment initiation." }, "verifiedAt": "2026-08-02" }, { "signal": "In the placebo-controlled crossover trial, local administration reactions were reported in 12 of 12 subjects (100%) during elamipretide treatment versus 8 of 12 (67%) during placebo. Injection site erythema was reported in 12 of 12 (100%) on elamipretide versus 3 of 12 (25%) on placebo. FDA's review records that injection site reactions were the most common adverse reactions and occurred in all 12 elamipretide-treated subjects.", "note": "The counts above are read directly from Table 2 of the label (Barth Safety Population, Periods 1 and 2 combined, N=12 per arm) and are corroborated in FDA's Integrated Review, which states: 'The most common adverse reactions were injection site reactions, which occurred in all 12 elamipretide treated subjects.' A 100% incidence is unusual enough to state plainly rather than round into 'the most common adverse reaction'. FDA's benefit-risk assessment characterises this as a tolerability issue rather than a life-threatening one.", "source": { "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/215244s000lbl.pdf", "title": "FORZINITY (elamipretide) injection, for subcutaneous use — Prescribing Information", "publisher": "FDA", "date": "2025-09-19", "quote": "Adverse reactions occurring more commonly on FORZINITY than on placebo include injection site reactions such as injection site erythema, pain, induration, pruritus, bruising, and urticaria (Table 2)." }, "verifiedAt": "2026-08-02" }, { "signal": "The FDA-approved labeling records that increases in absolute eosinophil counts were noted frequently in studies where the duration of administration was 30 days or greater, peaking around 90 days after initial exposure and returning to baseline after 6 to 12 months of continued treatment.", "note": "Quoted with a trailing ellipsis where the label gives a numeric magnitude, and truncated at a page break in the source PDF. FDA's Integrated Review adds the trial-level figure: 'Mild eosinophilia (>0.65×103 cells/uL) was observed in 9 of 12 elamipretide-treated subjects', and characterises the increases as apparently transient and not associated with clinical manifestations of eosinophilia. Recorded because it is a laboratory signal that only appears with continued exposure — nobody self-administering an unapproved vial is having eosinophil counts checked.", "source": { "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/215244s000lbl.pdf", "title": "FORZINITY (elamipretide) injection, for subcutaneous use — Prescribing Information", "publisher": "FDA", "date": "2025-09-19", "quote": "Increases in absolute eosinophil counts were noted frequently in studies where duration of administration of FORZINITY was 30 days or greater. Eosinophil counts generally peaked around 90 days after initial exposure … and returned to baseline levels after 6 to 12 months of" }, "verifiedAt": "2026-08-02" }, { "signal": "FDA has stated that the safety database in subjects with Barth syndrome is limited: safety was assessed in 12 subjects, the placebo-controlled safety data are limited to 12 weeks of exposure, and total cumulative exposure in the open-label extension was 26 subject-years across 10 subjects.", "note": "The number that puts every safety claim about this molecule in proportion. Twelve people with Barth syndrome received elamipretide in the programme that supported approval, and the controlled safety comparison covers a single 12-week period. FDA judged that database 'limited but acceptable given the rarity of the disease' — a judgement scaled to a 150-patient disease with no alternative. It is not a general safety clearance, and it cannot support any claim about the safety of long-term use in healthy adults, for whom the approved product was never studied and for whom two carcinogenicity studies remain outstanding as postmarketing requirements.", "source": { "url": "https://www.accessdata.fda.gov/drugsatfda_docs/nda/2025/215244Orig1s000IntegratedR.pdf", "title": "NDA 215244Orig1s000 — Integrated Review (NDA Re-submission Review), Forzinity (elamipretide)", "publisher": "FDA", "date": "2025-10-02", "quote": "Safety was assessed in 12 subjects with BTHS who received elamipretide including four adult and eight pediatric subjects. The placebo-controlled safety data are limited to 12 weeks of elamipretide exposure. … Total cumulative exposure was 26 subject-years; 7 subjects had greater than 144 weeks of exposure. … The safety database in subjects with BTHS is limited but acceptable given the rarity of the disease." }, "verifiedAt": "2026-08-02" } ], "faqs": [ { "question": "Is SS-31 the same thing as elamipretide?", "answer": "Yes. SS-31 is the Szeto-Schiller research designation for the peptide whose international nonproprietary name is elamipretide, and the two names are used interchangeably in the peer-reviewed literature — a 2023 paper in Antioxidants is titled 'Elamipretide(SS-31) Attenuates Idiopathic Pulmonary Fibrosis by Inhibiting the Nrf2-Dependent NLRP3 Inflammasome in Macrophages'. The same molecule also carried the development codes MTP-131 and Bendavia, both of which appear in its sponsor's own trial registrations, and it is sold as an FDA-approved drug under the brand name FORZINITY. The naming matters more than it sounds: someone searching 'SS-31' and a regulator searching 'elamipretide' are looking at one substance, and material sold as SS-31 is routinely discussed as though there were no FDA record of it. There is — an approved NDA, a published label, an approval letter and a full review.", "source": { "url": "https://pubmed.ncbi.nlm.nih.gov/38136142/", "title": "Elamipretide(SS-31) Attenuates Idiopathic Pulmonary Fibrosis by Inhibiting the Nrf2-Dependent NLRP3 Inflammasome in Macrophages (Nie Y, Li J, Zhai X, Wang Z)", "publisher": "PubMed", "date": "2023-11-21" }, "verifiedAt": "2026-08-02" }, { "question": "Is elamipretide FDA-approved in 2026?", "answer": "Yes, narrowly. FDA granted accelerated approval to FORZINITY (elamipretide) injection under NDA 215244 on 19 September 2025, to Stealth BioTherapeutics. The approval letter states that it 'is approved under accelerated approval pursuant to section 506(c) of the Federal Food, Drug, and Cosmetic Act (FDCA) and 21 CFR 314.510'. That is the whole of the approval: one application, one product, one indication — improving muscle strength in adult and pediatric patients with Barth syndrome weighing at least 30 kg. Barth syndrome is an X-linked mitochondrial disease that FDA's review puts at roughly 150 patients in the United States. Accelerated approval is a conditional pathway: FDA required a confirmatory randomized, placebo-controlled trial and stated in the same letter that if that trial 'fails to verify clinical benefit or is not conducted with due diligence … we may withdraw this approval.'", "source": { "url": "https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2025/215244Orig1s000ltr.pdf", "title": "NDA 215244 — ACCELERATED APPROVAL letter, Forzinity (elamipretide) injection", "publisher": "FDA", "date": "2025-09-19", "quote": "It is approved under accelerated approval pursuant to section 506(c) of the Federal Food, Drug, and Cosmetic Act (FDCA) and 21 CFR 314.510, effective on the date of this letter, for use as recommended in the enclosed agreed-upon labeling." }, "verifiedAt": "2026-08-02" }, { "question": "Did the elamipretide trial in Barth syndrome actually work?", "answer": "Not on its primary endpoints. The FDA-approved labeling for FORZINITY states, in section 14, that the randomized, double-blind, placebo-controlled crossover trial had primary endpoints of distance walked during the 6-minute walk test and total fatigue score on the Barth syndrome Symptom Assessment, and that 'FORZINITY was not superior to placebo on these primary endpoints.' FDA's Integrated Review gives the numbers: p=0.97 and p=0.89 respectively, and adds that 'none of the secondary endpoints achieved even nominal statistical significance (p=0.21-1.00).' The finding the approval rests on — increased knee extensor muscle strength measured by handheld dynamometry — came from somewhere else. The label is explicit: 'Increases in knee extensor muscle strength were not observed during the randomized trial but were observed during the extension period', an open-label, single-arm extension in which every participant knew they were receiving drug. That is why FDA treated muscle strength as an intermediate clinical endpoint reasonably likely to predict benefit, rather than as demonstrated benefit.", "source": { "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/215244s000lbl.pdf", "title": "FORZINITY (elamipretide) injection, for subcutaneous use — Prescribing Information", "publisher": "FDA", "date": "2025-09-19", "quote": "FORZINITY was not superior to placebo on these primary endpoints. … Increases in knee extensor muscle strength were not observed during the randomized trial but were observed during the extension period." }, "verifiedAt": "2026-08-02" }, { "question": "Did FDA's own reviewers agree that elamipretide should be approved?", "answer": "No. FDA's Integrated Review of the resubmitted application records that 'the clinical and biostatistical reviewers and the Cross-Discipline Team Leader (CDTL) conclude that there is not substantial evidence of effectiveness on knee muscle strength for accelerated approval and recommend a Complete Response action.' They cited the open-label design of the extension study, the lack of a control arm, and known and unknown sources of bias including subject attrition and effort-dependence. The signatory authority approved the application over that recommendation, writing that there is 'more uncertainty than we would accept for more common diseases' but that the uncertainty should be accepted 'in the context of this very rare (~150 subjects in the United States), serious disease with no approved treatments.' Both positions are in the same FDA document. Neither one is the whole story, and a page that quotes only 'FDA-approved' is quoting the shortest part of it.", "source": { "url": "https://www.accessdata.fda.gov/drugsatfda_docs/nda/2025/215244Orig1s000IntegratedR.pdf", "title": "NDA 215244Orig1s000 — Integrated Review (NDA Re-submission Review), Forzinity (elamipretide)", "publisher": "FDA", "date": "2025-10-02", "quote": "The clinical and biostatistical reviewers and the Cross-Discipline Team Leader (CDTL) conclude that there is not substantial evidence of effectiveness on knee muscle strength for accelerated approval and recommend a Complete Response action." }, "verifiedAt": "2026-08-02" }, { "question": "Is elamipretide or SS-31 approved for anti-aging, energy or mitochondrial health?", "answer": "No. The FDA-approved labeling for FORZINITY contains exactly one indication: 'FORZINITY is indicated to improve muscle strength in adult and pediatric patients with Barth syndrome weighing at least 30 kg.' There is no approved indication for ageing, fatigue, energy, exercise capacity, cognitive function, cardiac function or general mitochondrial support, and the label's second paragraph limits even the approved claim, stating the indication is granted 'under accelerated approval based on an improvement in knee extensor muscle strength, an intermediate clinical endpoint' whose continued approval 'may be contingent upon verification and description of clinical benefit in a confirmatory trial.' FDA's review is blunter still about the reach of that endpoint: it 'involves only a single muscle group (knee extensor muscles) and is not accompanied by substantial evidence demonstrating an effect of elamipretide on an appropriate functional measure or on any endpoints directly measuring clinical benefit.' A Phase 2a open-label pilot in older adults did begin at the University of Washington in November 2025 (NCT07275424), which is what an unanswered question looks like, not an answer.", "source": { "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/215244s000lbl.pdf", "title": "FORZINITY (elamipretide) injection, for subcutaneous use — Prescribing Information", "publisher": "FDA", "date": "2025-09-19", "quote": "FORZINITY is indicated to improve muscle strength in adult and pediatric patients with Barth syndrome weighing at least 30 kg. This indication is approved under accelerated approval based on an improvement in knee extensor muscle strength, an intermediate clinical endpoint [see Clinical Studies (14)]." }, "verifiedAt": "2026-08-02" }, { "question": "What happened to the elamipretide Phase 3 trial in mitochondrial myopathy?", "answer": "It was terminated for missing its primary endpoints. MMPOWER-3 (NCT03323749) was a Phase 3 randomized, placebo-controlled trial of subcutaneous elamipretide in subjects with primary mitochondrial myopathy, sponsored by Stealth BioTherapeutics, with an actual enrolment of 218. Its registry record carries status TERMINATED with the sponsor's own stated reason: 'Part1,double blind portion of the trial did not meet the primary end points.' Primary completion is recorded as 2020-02-10, and results were first posted 2021-04-02. This matters for how the compound is described elsewhere: the genuine Phase 3 programme for elamipretide was in mitochondrial myopathy and it failed, while the Barth syndrome trial behind the FDA approval was a 12-subject crossover trial whose own official title calls it Phase 2. A separate Phase 3 in dry age-related macular degeneration (ReNEW, NCT06373731) was listed as active and not recruiting as of May 2026, with estimated primary completion in August 2027 and no result yet.", "source": { "url": "https://clinicaltrials.gov/study/NCT03323749", "title": "MMPOWER-3 — A Phase 3 Randomized, Placebo-Controlled Trial to Evaluate the Efficacy and Safety of Daily Subcutaneous Injections of Elamipretide in Subjects With Primary Mitochondrial Myopathy Followed by an Open-Label Treatment Extension", "publisher": "ClinicalTrials.gov", "date": "2022-01-24", "quote": "Part1,double blind portion of the trial did not meet the primary end points." }, "verifiedAt": "2026-08-02" }, { "question": "Can the FDA approval of elamipretide be withdrawn?", "answer": "Yes — that is a written condition of this particular approval. The FDA approval letter for NDA 215244 states: 'If your required postmarketing clinical trial fails to verify clinical benefit or is not conducted with due diligence, including with respect to the conditions set forth below, we may withdraw this approval.' The required trial is postmarketing requirement 4802-1, 'a randomized, double-blind, placebo-controlled trial in patients 5 years and older with Barth syndrome to verify and describe the clinical benefit of Forzinity predicted by improvements in knee extensor muscle strength assessed by handheld dynamometry.' The agreed timetable in the letter runs to study completion in September 2029 and a final report in March 2030. FDA also noted in its review that it granted the approval 'even though the post-approval confirmatory trial is not underway' at the time; that trial, registered as NCT07531251, records an actual start date of 2 July 2026. Until it reports, the clinical benefit remains, in FDA's framing, predicted rather than verified.", "source": { "url": "https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2025/215244Orig1s000ltr.pdf", "title": "NDA 215244 — ACCELERATED APPROVAL letter, Forzinity (elamipretide) injection", "publisher": "FDA", "date": "2025-09-19", "quote": "If your required postmarketing clinical trial fails to verify clinical benefit or is not conducted with due diligence, including with respect to the conditions set forth below, we may withdraw this approval." }, "verifiedAt": "2026-08-02" }, { "question": "Is elamipretide on FDA's 503A list of bulk drug substances for compounding?", "answer": "No. Elamipretide appears in none of Categories 1, 2 or 3 of FDA's list of bulk drug substances nominated for use in compounding under section 503A, in the version updated 14 May 2026 — and neither do the names SS-31, MTP-131 or Bendavia. Read what that absence does and does not mean. It is not permission and it is not a safety finding. The 503A nomination route exists for substances that have no FDA-approved product; elamipretide has one, so it was never part of that process, which is a different situation from a peptide such as BPC-157 that was nominated and then left Category 2 when its nominators withdrew. For the same reason this record deliberately records no 503A status at all rather than labelling elamipretide 'never-nominated', which would imply a proceeding it was never in.", "source": { "url": "https://www.fda.gov/media/94155/download", "title": "Bulk Drug Substances Nominated for Use in Compounding Under Section 503A of the Federal Food, Drug, and Cosmetic Act", "publisher": "FDA", "date": "2026-05-14" }, "verifiedAt": "2026-08-02" } ] }, { "slug": "emideltide", "name": "Emideltide (DSIP)", "aliases": [ "DSIP", "Delta Sleep-Inducing Peptide", "Delta Sleeping Inducing Peptide", "Emideltide acetate", "Emideltide (free base)" ], "url": "https://peptides101.com/compounds/emideltide", "moleculeNote": "'Emideltide' is the INN; the briefing document states verbatim: 'Emideltide is also referred to as Delta Sleeping Inducing Peptide (DSIP).' Nearly all consumer-facing material uses DSIP. Reported to be a nonapeptide. FDA evaluates two related substances — emideltide (free base) and emideltide acetate — because the nominators gave inconsistent information and it is unclear which they intended to nominate. Neither has a USP or NF monograph, and neither is a component of an FDA-approved drug. ROUTE IS THE DECISIVE VARIABLE, not molecule: every human study FDA identified administered emideltide INTRAVENOUSLY. The nominated route — the route compounded products were PROPOSED for — is SUBCUTANEOUS, at 1000 mcg/mL. FDA found no clinical studies of any kind for the SC route. Human data on one route is not human data on another. FDA describes the products it found on sale as 'injection and intranasal' without stating the injectables are subcutaneous.", "quickAnswer": "Emideltide (DSIP) is not FDA-approved, is not a registered drug in any country FDA searched, and appears nowhere on FDA's 503A bulks list — so it may not lawfully be used in 503A compounding for any use. FDA identified studies that administered emideltide intravenously to 209 subjects and found 'insufficient evidence concerning effectiveness' for chronic insomnia, narcolepsy and opioid withdrawal, the three uses it evaluated; for the subcutaneous route emideltide was nominated for, FDA identified no clinical studies of any kind.", "fdaStatus": { "value": "not-approved", "note": "Not an FDA-approved drug for any indication, and not in active development toward approval. That says nothing about whether it is sold — it is.", "source": { "url": "https://www.fda.gov/media/193344/download", "title": "Emideltide (DSIP)-Related Bulk Drug Substances — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, July 23-24, 2026", "publisher": "FDA", "date": "2026-07-23", "quote": "The nominations were withdrawn, and FDA is evaluating the substances at its discretion." }, "verifiedAt": "2026-07-16" }, "compoundingStatus": { "value": "withdrawn-from-nomination", "note": "The WITHDRAWAL is established by the briefing document quoted above, not by the bulks list. That distinction is load-bearing: absence from the 503A list shows only that a substance is in none of the three categories. It cannot by itself tell withdrawn-from-nomination apart from never-nominated, or from an approved drug that was never on the nomination track at all. This record cites the document that names the withdrawal. Two nominations were filed — Wells Pharmacy Network (FDA-2015-N-3534-0287) and LDT Health Solutions, Inc. (FDA-2018-N-2973-0002) — and the briefing document's footnote 3 records both as withdrawn (FDA-2015-N-3534-0484 and -0485). One detail cuts specifically against the 'nomination withdrawn, so FDA dropped it' reading: FDA did not drop it. It is 'evaluating the substances at its discretion', and it still considered the withdrawn nominators' own submitted information as part of that evaluation. The withdrawal removed the sponsor, not the scrutiny.", "source": { "url": "https://www.fda.gov/media/193344/download", "title": "Emideltide (DSIP)-Related Bulk Drug Substances — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, July 23-24, 2026", "publisher": "FDA", "date": "2026-07-23", "quote": "The nominations were withdrawn, and FDA is evaluating the substances at its discretion." }, "verifiedAt": "2026-07-16" }, "evidence": { "tier": "promising-but-unproven", "humanAdministrationChecked": true, "note": "ADMINISTRATION CHECK: passed, and this is the rare record where it passes. FDA's briefing document states directly that it identified studies which ADMINISTERED IV emideltide to humans — 209 subjects, 25-150 nmol/kg, 1 to 15 days. This is not the MOTS-c/TB-500 pattern of endogenous peptide measured as a biomarker; the drug was given to people. Provenance caveat, stated plainly: the administration finding is verified against FDA's evaluation of the underlying literature, which is a primary regulatory source that summarises each study's design and route; we did not independently open Schneider-Helmert and Schoenenberger 1981, Bes 1992 or Schneider-Helmert 1987. WHY 'PROMISING' IS THE CEILING AND NOT AN ENDORSEMENT — the human trials are small, from the 1980s-90s, and contradict each other. In a 1981 randomised, double-blind, placebo-controlled crossover study of six middle-aged subjects with chronic insomnia, researchers reported 'tendencies toward a lower NOA and a higher total SE', with no effect on sleep onset latency or final waking times. Limitations: n=6, intra-subject comparison on sequential nights, results reported as p values without numerical data for placebo, and possible carryover — the same group reported delayed effects 13-22 hours after administration. In a 1992 double-blind placebo-controlled study of 16 subjects with chronic insomnia, researchers reported that short-term IV treatment 'had little therapeutic benefit'; no significant difference in objective sleep measures or subjective sleep quality versus placebo. In Schneider-Helmert 1987, a study of 14 middle-aged subjects with chronic insomnia, researchers reported improved sleep induction and maintenance — but FDA re-classified its design: the authors called it 'placebo-controlled' when 'there was no placebo arm in the study', comparison being against an external matched control group of healthy subjects. FDA read that design as 'externally matched controlled'. (Monti 1987 is a DIFFERENT 1987 study and is not the one with the design problem: FDA describes it as an 'R, DB, PC, CO study' in six subjects with severe chronic insomnia over nine nights, and it did have a placebo arm.) FDA's overall conclusion: 'there is insufficient evidence concerning effectiveness to support the use of emideltide (free base) or emideltide acetate via the IV ROA for the treatment of chronic insomnia, narcolepsy, and opioid withdrawal. Clinical studies for chronic insomnia appear to be inconclusive and at best preliminary.' Note what the tier does NOT transfer to: the trials above are all INTRAVENOUS. For the proposed subcutaneous route, the human evidence base is empty, not thin. No ClinicalTrials.gov registration is cited here — FDA searched that registry itself as part of this evaluation, which is a better source than a self-reported registration.", "source": { "url": "https://www.fda.gov/media/193344/download", "title": "Emideltide (DSIP)-Related Bulk Drug Substances — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, July 23-24, 2026", "publisher": "FDA", "date": "2026-07-23", "quote": "We identified several studies that administered IV emideltide to humans. For the list of references and details of the studies refer to Appendix 6. Based on these clinical studies, doses of emideltide between 25 – 150 nmol/kg have been administered intravenously to 209 subjects for 1 to 15 days." }, "verifiedAt": "2026-07-16" }, "fdaApproval": null, "fdaFindings": [ { "finding": "Emideltide appears nowhere on the 503A bulks list — not in Category 1, 2 or 3 — in the list updated 2026-05-14. It therefore may not lawfully be used in 503A compounding for any use.", "note": "Verified by fetching and text-extracting the document directly and searching it for 'emideltide', 'DSIP' and 'delta sleep': zero hits. Read this for exactly what it says and nothing more. The non-compoundability follows from ABSENCE FROM THE LIST itself — a substance not on the list may not be used in 503A compounding, full stop. It does not follow from the scope of FDA's evaluation, and the absence is not a safety finding, not a green light, and not evidence about the molecule either way. Category 2 contains exactly six substances: Cesium Chloride, Domperidone, Germanium Sesquioxide, Ibutamoren Mesylate, Kisspeptin-10, and Quinacrine Hydrochloride for intrauterine administration. Emideltide is not among them — but note that Category 2 is not free of consumer peptides: Kisspeptin-10 is a peptide, and ibutamoren (MK-677) is sold throughout this same market.", "source": { "url": "https://www.fda.gov/media/94155/download", "title": "Bulk Drug Substances Nominated for Use in Compounding Under Section 503A of the Federal Food, Drug, and Cosmetic Act", "publisher": "FDA", "date": "2026-05-14" }, "verifiedAt": "2026-07-16" }, { "finding": "FDA staff propose not adding emideltide (free base) or emideltide acetate to the 503A Bulks List, ahead of the Pharmacy Compounding Advisory Committee meeting on 23-24 July 2026.", "note": "A staff proposal is not a final determination. The briefing document states: 'The FDA will not issue a final determination on the issues at hand until input from the advisory committee process has been considered and all reviews have been finalized.' The stated grounds are three, not one: 'lack of data related to physiochemical characterization, lack of evidence of effectiveness and insufficient safety information'.", "source": { "url": "https://www.fda.gov/media/193344/download", "title": "Emideltide (DSIP)-Related Bulk Drug Substances — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, July 23-24, 2026", "publisher": "FDA", "date": "2026-07-23", "quote": "Accordingly, we propose not adding emideltide (free base) or emideltide acetate to the 503A Bulks List." }, "verifiedAt": "2026-07-16" }, { "finding": "FDA evaluated emideltide for THREE uses — opioid withdrawal, chronic insomnia and narcolepsy — and declined to evaluate 'paradoxical sleep disorder' because the nominations did not include sufficient information.", "note": "The sleep framing that dominates consumer material understates the scope of what FDA looked at. Emideltide was nominated for 'insomnia'; FDA narrowed to 'chronic insomnia' because that was the condition discussed in the nominators' own submitted references. As with BPC-157, the declined use is an EVIDENTIARY VACUUM RATHER THAN AN OPEN QUESTION: FDA did not skip paradoxical sleep disorder because it sits outside FDA's remit, but because the nominations 'did not include sufficient information for the Agency' to evaluate it. That cuts against the sleep-market claims, not for them. Separately, and regardless of which uses were evaluated: emideltide is not on the 503A bulks list, so it may not lawfully be used in 503A compounding for ANY use — including the one FDA never assessed. That follows from its absence from the list itself, not from the scope of FDA's evaluation.", "source": { "url": "https://www.fda.gov/media/193344/download", "title": "Emideltide (DSIP)-Related Bulk Drug Substances — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, July 23-24, 2026", "publisher": "FDA", "date": "2026-07-23" }, "verifiedAt": "2026-07-16" }, { "finding": "FDA identified no clinical studies whatsoever — effectiveness or safety — for the nominated subcutaneous route, the route in which compounded products were proposed at 1000 mcg/mL.", "note": "This is the finding most likely to be laundered by omission. Human IV data exists and is genuine; it says nothing about the subcutaneous product. FDA also flagged that it is 'unclear how it would be possible to formulate the proposed injectable dosage form with concentration of 1,000 mcg/ml without co-solvent used', given limited water solubility — a formulation objection on top of the evidentiary one.", "source": { "url": "https://www.fda.gov/media/193344/download", "title": "Emideltide (DSIP)-Related Bulk Drug Substances — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, July 23-24, 2026", "publisher": "FDA", "date": "2026-07-23", "quote": "Clinical studies were not identified that had information for emideltide (free base) or emideltide acetate for the proposed SC ROA." }, "verifiedAt": "2026-07-16" }, { "finding": "FDA found the published literature 'too limited to inform the historical use of any form of emideltide compounded drug' products.", "note": "Relevant to the common 'it has decades of use behind it' claim. Decades of published IV research in a laboratory setting is not a record of compounded use.", "source": { "url": "https://www.fda.gov/media/193344/download", "title": "Emideltide (DSIP)-Related Bulk Drug Substances — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, July 23-24, 2026", "publisher": "FDA", "date": "2026-07-23" }, "verifiedAt": "2026-07-16" }, { "finding": "Emideltide (free base) and emideltide acetate are not registered drugs in ANY country FDA searched, and no form of emideltide is recognised in the European, Japanese or International Pharmacopoeia.", "note": "This closes the 'approved somewhere else' escape hatch, which is the standard fallback once the US position is conceded. The briefing document states verbatim: 'No form of emideltide is recognized in the European Pharmacopoeia (11th Edition, 11.8), the Japanese Pharmacopoeia (18th Edition), or the International Pharmacopoeia (11th Edition).' It further records: 'There is no applicable United States Pharmacopeia (USP) or National Formulary (NF) drug substance monograph for emideltide (free base) or its acetate form, and neither is a component of an FDA-approved drug.' Note what this is NOT: a finding about the molecule. Non-registration is a statement about the regulatory record, not about pharmacology.", "source": { "url": "https://www.fda.gov/media/193344/download", "title": "Emideltide (DSIP)-Related Bulk Drug Substances — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, July 23-24, 2026", "publisher": "FDA", "date": "2026-07-23", "quote": "Emideltide (free base) and emideltide acetate are not registered drugs in any country searched via GlobalEdge." }, "verifiedAt": "2026-07-16" }, { "finding": "An online search by FDA did not identify ANY compounding pharmacies marketing emideltide-related compounded preparations — yet emideltide injection and intranasal products are available in the US through integrative neurology clinics, medical concierge services, medical spas, wellness clinics and online retailers.", "note": "The two halves of this finding are both FDA's, and the gap between them is the whole market. FDA found the substance widely available and simultaneously could not find a compounding pharmacy openly marketing it — and stated it is 'unclear whether these products are compounded or if pharmacies are currently compounding products containing emideltide-related BDS.' AVAILABILITY IS NOT LEGALITY. That a med spa will sell it establishes nothing about lawful status; emideltide is absent from the 503A bulks list either way. FDA did find that emideltide-related substances 'have been used in compounding since at least 2018' and 'have been studied for use in humans since at least 1981' — so the historical-use question is genuinely mixed, and this record should not flatten it. FDA's conclusion was that the literature is nonetheless too limited to inform that use.", "source": { "url": "https://www.fda.gov/media/193344/download", "title": "Emideltide (DSIP)-Related Bulk Drug Substances — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, July 23-24, 2026", "publisher": "FDA", "date": "2026-07-23", "quote": "An online search did not identify any compounding pharmacies marketing emideltide-related compounded preparations." }, "verifiedAt": "2026-07-16" }, { "finding": "The nominators' stated reason for compounding emideltide was that there is 'no FDA-approved product available' — a justification FDA rejected in the same document, finding that approved drugs exist for all three conditions evaluated.", "note": "The nomination package reproduced in the briefing document answers the question 'What is the reason for use of a compounded drug product rather than an FDA-approved product?' with: 'no FDA-approved product available'. FDA's own conclusion contradicts it directly, and the existence of approved alternatives is load-bearing in FDA's reasoning rather than incidental. Note that FDA's sentence has a compound subject — the approved drugs are one of two limbs, not the sole grounds: 'The lack of data discussed above, and the existence of FDA-approved drugs to treat chronic insomnia, narcolepsy, and opioid withdrawal, particularly considering these are serious and/or life-threatening conditions, weighs against emideltide-related BDSs being added to the 503A Bulks List.' For opioid withdrawal specifically FDA is blunter still: 'There are FDA approved therapies with established efficacy for opioid withdrawal.' The nominator's premise was false, and the falsity of it counted against the nomination.", "source": { "url": "https://www.fda.gov/media/193344/download", "title": "Emideltide (DSIP)-Related Bulk Drug Substances — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, July 23-24, 2026", "publisher": "FDA", "date": "2026-07-23", "quote": "At the time of this evaluation, there are FDA-approved drugs for treating serious conditions like insomnia, narcolepsy, and opioid withdrawal in adults." }, "verifiedAt": "2026-07-16" } ], "safetySignals": [ { "signal": "A FAERS search for adverse events for emideltide through 3 March 2024 retrieved ZERO reports, and FDA identified no relevant case reports in the medical literature.", "note": "Zero FAERS reports is an ABSENCE OF DATA, NOT A FINDING OF SAFETY, and the difference is the whole point. FAERS is a passive, voluntary system; substances bought as research chemicals and self-administered outside clinical care generate few reports by construction, because there is usually no clinician in the loop to file one. FDA drew no safety conclusion from the zero and still proposed not adding the substance, citing 'insufficient safety information'. Anyone citing the zero as a clean safety record has inverted it.", "source": { "url": "https://www.fda.gov/media/193344/download", "title": "Emideltide (DSIP)-Related Bulk Drug Substances — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, July 23-24, 2026", "publisher": "FDA", "date": "2026-07-23", "quote": "The Office of Surveillance and Epidemiology conducted a search of the FAERS database for reports of adverse events (AEs) for emideltide through March 3, 2024. The search retrieved zero reports." }, "verifiedAt": "2026-07-16" }, { "signal": "In a 1984 study of IV emideltide in 107 subjects with alcohol or opiate withdrawal syndrome, three subjects experienced serious adverse effects: two had hypotension at the beginning of the first injection, and one had repetitive episodes of general discomfort with perspiration and nausea lasting 15 minutes. One of those three subjects, who received a second injection, experienced 'progressive hypotension'. Nine subjects had minor transient side effects including perspiration, headaches, nausea and vertigo.", "note": "The only serious adverse events in the human record come from the withdrawal population, not the insomnia population — and FDA carried them into its summary conclusion, noting 'cases of hypotension that was \"progressive\" following second emideltide injection administered IV'. There was no additional information for the subject with progressive hypotension.", "source": { "url": "https://www.fda.gov/media/193344/download", "title": "Emideltide (DSIP)-Related Bulk Drug Substances — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, July 23-24, 2026", "publisher": "FDA", "date": "2026-07-23" }, "verifiedAt": "2026-07-16" }, { "signal": "IV emideltide in small numbers of subjects with chronic insomnia was reported well tolerated and not associated with significant adverse events.", "note": "Recorded because the record should not be shaded in either direction. Scope limits: 'small numbers of subjects', intravenous, short-term (1 to 15 days across the whole literature), and no data on long-term administration. FDA nonetheless concluded that safety 'is insufficiently characterized'.", "source": { "url": "https://www.fda.gov/media/193344/download", "title": "Emideltide (DSIP)-Related Bulk Drug Substances — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, July 23-24, 2026", "publisher": "FDA", "date": "2026-07-23" }, "verifiedAt": "2026-07-16" }, { "signal": "The substances are not well characterised physically and chemically; endotoxin testing for the injectable route is lacking, and FDA identified no information addressing potential aggregation and immunogenicity risks.", "note": "No bioburden or endotoxin test is mentioned in the certificate of analysis provided by the nominator. Endotoxin testing is a critical quality attribute for a bulk drug substance intended for injection. This is a manufacturing-quality gap that is independent of whether the molecule works: an effectiveness verdict, favourable or not, would not close it. FDA lists it first among its three stated grounds — 'lack of data related to physiochemical characterization' — ahead of both the effectiveness and the safety grounds.", "source": { "url": "https://www.fda.gov/media/193344/download", "title": "Emideltide (DSIP)-Related Bulk Drug Substances — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, July 23-24, 2026", "publisher": "FDA", "date": "2026-07-23" }, "verifiedAt": "2026-07-16" }, { "signal": "FDA flagged that emideltide's stimulation of the opioid system 'could lead to development of addiction', and identified no nonclinical studies addressing that potential.", "note": "Almost entirely absent from consumer material, which frames emideltide as a benign sleep peptide. The mechanism cuts both ways in FDA's own telling: the briefing document notes emideltide 'does not appear to interact directly with opioid receptors' but 'can stimulate calcium-dependent release of endorphins', and that this opioid-system stimulation 'could potentially be beneficial to suppress signs and symptoms of alcohol and opioid withdrawal syndromes'. The same mechanism proposed as the therapeutic rationale is the one FDA names as an addiction concern. Read the finding precisely: FDA identified a THEORETICAL risk and an ABSENCE OF STUDIES, not a documented case of dependence. That is not reassurance — an unstudied risk is unquantified, not absent.", "source": { "url": "https://www.fda.gov/media/193344/download", "title": "Emideltide (DSIP)-Related Bulk Drug Substances — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, July 23-24, 2026", "publisher": "FDA", "date": "2026-07-23", "quote": "However, stimulation of the opioid system by emideltide-related BDSs could lead to development of addiction, and, at the time of this evaluation, FDA did not identify nonclinical studies to inform the potential addictive potential of emideltide-related BDSs." }, "verifiedAt": "2026-07-16" }, { "signal": "No nonclinical toxicity studies exist: the nominator submitted none and FDA identified none, including no developmental or reproductive toxicity studies.", "note": "The foundation the human IV data does not sit on. Ordinary drug development runs animal toxicology BEFORE human exposure; here the 1980s human trials exist and the toxicology underneath them does not. FDA separately records that it 'did not identify nonclinical developmental and reproductive studies' of either substance. On carcinogenicity, FDA rejected the one favourable nominator-submitted result as uninterpretable: findings that Deltaran (a product containing emideltide free base AND glycine) reduced chromosome aberrations and spontaneous malignant tumour incidence in female SHR mice 'could not be interpreted as evidence that emideltide-related BDSs have no potential to trigger genotoxicity or carcinogenicity in part because glycine has been reported to have antimutagenic and anticarcinogenic properties'. The confound is that the co-formulated ingredient could account for the effect — so the study cannot clear the peptide.", "source": { "url": "https://www.fda.gov/media/193344/download", "title": "Emideltide (DSIP)-Related Bulk Drug Substances — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, July 23-24, 2026", "publisher": "FDA", "date": "2026-07-23", "quote": "At the time of this evaluation, the nominator did not submit, and FDA did not identify nonclinical toxicity studies to inform safety considerations for potential clinical uses of emideltide (free base) or emideltide acetate." }, "verifiedAt": "2026-07-16" } ], "faqs": [ { "question": "Is DSIP legal in 2026?", "answer": "Emideltide (DSIP) appears nowhere on FDA's 503A bulks list — not in Category 1, 2 or 3 — on the list updated 14 May 2026, and a substance absent from that list may not lawfully be used in 503A compounding for any indication. Absence from the list is not a safety finding and not a green light; it means emideltide has no lawful route into a 503A compounded preparation, and says nothing either way about the molecule.", "source": { "url": "https://www.fda.gov/media/94155/download", "title": "Bulk Drug Substances Nominated for Use in Compounding Under Section 503A of the Federal Food, Drug, and Cosmetic Act", "publisher": "FDA", "date": "2026-05-14" }, "verifiedAt": "2026-07-16" }, { "question": "Did DSIP become legal again when the nominations were withdrawn?", "answer": "No. The two nominations to add emideltide (DSIP) to FDA's 503A bulks list were withdrawn, but FDA's briefing document for the July 2026 Pharmacy Compounding Advisory Committee meeting states that FDA 'is evaluating the substances at its discretion' and that it considered the withdrawn nominators' own submitted information as part of that evaluation. The withdrawal removed the sponsor, not the scrutiny: emideltide remains absent from the 503A bulks list, so it still may not lawfully be used in 503A compounding. Withdrawal moved its status sideways, not toward legality.", "source": { "url": "https://www.fda.gov/media/193344/download", "title": "Emideltide (DSIP)-Related Bulk Drug Substances — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, July 23-24, 2026", "publisher": "FDA", "date": "2026-07-23", "quote": "The nominations were withdrawn, and FDA is evaluating the substances at its discretion." }, "verifiedAt": "2026-07-16" }, { "question": "Did FDA approve DSIP?", "answer": "No. Emideltide (DSIP) has no FDA approval, and FDA's July 2026 briefing document states that 'Emideltide (free base) and emideltide acetate are not registered drugs in any country searched via GlobalEdge.' No form of emideltide is recognised in the European, Japanese or International Pharmacopoeia, there is no applicable USP or NF drug substance monograph for either form, and neither is a component of an FDA-approved drug.", "source": { "url": "https://www.fda.gov/media/193344/download", "title": "Emideltide (DSIP)-Related Bulk Drug Substances — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, July 23-24, 2026", "publisher": "FDA", "date": "2026-07-23", "quote": "Emideltide (free base) and emideltide acetate are not registered drugs in any country searched via GlobalEdge." }, "verifiedAt": "2026-07-16" }, { "question": "Is there any human evidence that DSIP works for sleep?", "answer": "There is real human data on emideltide (DSIP), and FDA judged it insufficient. FDA's July 2026 briefing document states it identified studies that administered emideltide intravenously to 209 subjects, and concluded: 'Based on available clinical data, there is insufficient evidence concerning effectiveness to support the use of emideltide (free base) or emideltide acetate via the IV ROA for the treatment of chronic insomnia, narcolepsy, and opioid withdrawal. Clinical studies for chronic insomnia appear to be inconclusive and at best preliminary.' FDA noted the studies that showed a positive response 'had poor study methodologies'. Every one of those trials was intravenous; for the subcutaneous route DSIP was nominated for, FDA identified no clinical studies at all.", "source": { "url": "https://www.fda.gov/media/193344/download", "title": "Emideltide (DSIP)-Related Bulk Drug Substances — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, July 23-24, 2026", "publisher": "FDA", "date": "2026-07-23", "quote": "Based on available clinical data, there is insufficient evidence concerning effectiveness to support the use of emideltide (free base) or emideltide acetate via the IV ROA for the treatment of chronic insomnia, narcolepsy, and opioid withdrawal. Clinical studies for chronic insomnia appear to be inconclusive and at best preliminary." }, "verifiedAt": "2026-07-16" }, { "question": "Can I get DSIP from a compounding pharmacy?", "answer": "There is no lawful route: emideltide (DSIP) is absent from FDA's 503A bulks list, so it may not lawfully be used in 503A compounding for any use. FDA's July 2026 briefing document reports that 'An online search did not identify any compounding pharmacies marketing emideltide-related compounded preparations' — while also recording that emideltide injection and intranasal products are available in the US through integrative neurology clinics, medical concierge services, medical spas, wellness clinics and online retailers. That a clinic will sell it establishes nothing about its lawful status.", "source": { "url": "https://www.fda.gov/media/193344/download", "title": "Emideltide (DSIP)-Related Bulk Drug Substances — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, July 23-24, 2026", "publisher": "FDA", "date": "2026-07-23", "quote": "An online search did not identify any compounding pharmacies marketing emideltide-related compounded preparations." }, "verifiedAt": "2026-07-16" }, { "question": "Is DSIP safe?", "answer": "Emideltide (DSIP) safety is, in FDA's own words, 'insufficiently characterized'. A FAERS search for adverse events through 3 March 2024 retrieved zero reports — an absence of data, not a finding of safety, since FAERS is passive and voluntary. FDA identified no nonclinical toxicity studies of either emideltide form, no developmental or reproductive toxicity studies, and no clinical safety data for the subcutaneous route. In a 1984 study of intravenous emideltide in 107 subjects with alcohol or opiate withdrawal, three subjects experienced serious adverse effects: two had hypotension at the beginning of the first injection, and a third had repetitive episodes of general discomfort with perspiration and nausea lasting 15 minutes. One of those three, after a second injection, experienced what FDA quoted as 'progressive hypotension'. FDA also flagged that emideltide's stimulation of the opioid system 'could lead to development of addiction' and that no nonclinical studies address it.", "source": { "url": "https://www.fda.gov/media/193344/download", "title": "Emideltide (DSIP)-Related Bulk Drug Substances — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, July 23-24, 2026", "publisher": "FDA", "date": "2026-07-23", "quote": "Considering that the context of use may be for chronic intermittent use, safety for emideltide-related products is insufficiently characterized." }, "verifiedAt": "2026-07-16" }, { "question": "What did FDA propose at the July 2026 PCAC meeting about DSIP?", "answer": "FDA staff proposed NOT adding it. The FDA briefing document for the Pharmacy Compounding Advisory Committee meeting on 23-24 July 2026 states: 'Accordingly, we propose not adding emideltide (free base) or emideltide acetate to the 503A Bulks List.' The stated grounds are three — 'lack of data related to physiochemical characterization, lack of evidence of effectiveness and insufficient safety information'. A staff proposal is not a final determination: the same document states FDA 'will not issue a final determination on the issues at hand until input from the advisory committee process has been considered and all reviews have been finalized.'", "source": { "url": "https://www.fda.gov/media/193344/download", "title": "Emideltide (DSIP)-Related Bulk Drug Substances — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, July 23-24, 2026", "publisher": "FDA", "date": "2026-07-23", "quote": "Accordingly, we propose not adding emideltide (free base) or emideltide acetate to the 503A Bulks List." }, "verifiedAt": "2026-07-16" } ] }, { "slug": "epitalon", "name": "Epitalon", "aliases": [ "Epithalon", "AEDG peptide", "Ala-Glu-Asp-Gly", "Epitalon acetate", "Epitalon (free base)" ], "url": "https://peptides101.com/compounds/epitalon", "moleculeNote": "A synthetic tetrapeptide (Ala-Glu-Asp-Gly). FDA evaluates two related substances: epitalon (free base) and epitalon acetate — and notes the nominators' own packages were internally inconsistent about WHICH of the two they meant, with each Certificate of Analysis naming one substance in the title and a different one by molecular weight/formula. Separately, and more consequentially for readers: EPITALON AND EPITHALAMIN ARE NOT THE SAME SUBSTANCE. Epithalamin is a polypeptide complex extracted from animal (bovine/calf) pineal gland; epitalon is a synthetic tetrapeptide first synthesised around 1999 precisely because calf pineal gland was in limited supply. FDA states it 'considers epitalon and epithalamin as different substances', and epithalamin is not listed as a synonym for epitalon under UNII O65P17785G. This matters because seven of the articles the nominators submitted in support of epitalon studied epithalamin instead. Marketing copy that cites the human 'pineal peptide prolongs life' literature is frequently citing the animal-extract substance, not the peptide in the vial.", "quickAnswer": "Epitalon is not an FDA-approved drug and is not a component of one, it has no USP or NF monograph, and FDA staff proposed, in their briefing document for the Pharmacy Compounding Advisory Committee meeting of 23-24 July 2026, not to add epitalon (free base) or epitalon acetate to the 503A bulks list — which would leave all three routes to eligibility under section 503A closed. It is absent from that list today because both nominations were withdrawn by the nominators, not because it was cleared. FDA's literature search found three published studies that administered epitalon to humans — one of them randomised and placebo-controlled — but all used sublingual or parabulbar routes rather than the subcutaneous injection the nominations proposed; FDA states it 'did not identify studies evaluating the use of these substances in patients with insomnia', and that the one study measuring a melatonin metabolite 'did not evaluate sleep outcomes'. FDA concluded there are no clinical data supporting the safety of either substance in humans, and found no pharmacokinetic data at all.", "fdaStatus": { "value": "not-approved", "note": "Not an FDA-approved drug for any indication, and not in active development toward approval. That says nothing about whether it is sold — it is.", "source": { "url": "https://www.fda.gov/media/193345/download", "title": "Epitalon-Related Bulk Drug Substances — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, July 23-24, 2026", "publisher": "FDA", "date": "2026-07-23" }, "verifiedAt": "2026-07-16" }, "compoundingStatus": { "value": "withdrawn-from-nomination", "note": "Absent from Categories 1, 2 and 3 in the list updated 2026-05-14 — verified by fetching and text-extracting the document directly. Category 2 contains exactly six substances, none of them epitalon. (Corrected 2026-07-16: this note previously said no consumer peptide was among the six, which is false — Kisspeptin-10 is a peptide and ibutamoren mesylate is sold throughout this same market. The accurate statement is narrower: none of the seven peptides before PCAC on 2026-07-23/24 is in Category 2. They are absent from the list entirely.) Epitalon was nominated (twice — Wells Pharmacy Network, and LDT Health Solutions on behalf of the International Peptide Society) and BOTH NOMINATIONS WERE WITHDRAWN by the nominators. That is why it is off the list: withdrawal, not legalisation. It did not enter Category 1, it is not on the 503A bulks list, and it remains non-compoundable. Note the unusual posture: FDA is evaluating epitalon ON ITS OWN INITIATIVE despite the withdrawals, and considered the withdrawn nomination materials as part of that evaluation — so withdrawal did not end FDA's scrutiny, it merely removed the nominators from it.", "source": { "url": "https://www.fda.gov/media/193345/download", "title": "Epitalon-Related Bulk Drug Substances — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, July 23-24, 2026", "publisher": "FDA", "date": "2026-07-23" }, "verifiedAt": "2026-07-16" }, "evidence": { "tier": "promising-but-unproven", "humanAdministrationChecked": true, "note": "ADMINISTRATION CHECK RUN AND PASSED — and it changes the answer. FDA's briefing document states verbatim: 'three studies were found in which epitalon was administered to humans.' These are NOT endogenous-biomarker studies (the trap that reduces MOTS-c and TB-500 to zero); the peptide was given to people. The strongest is Ivko et al. 2021, which FDA describes as 'a randomized, placebo-controlled study' of healthy women aged 40-50 primarily working night shifts (n = 75 screened; 40 with low melatonin-metabolite excretion randomised to peptide or saline placebo for 20 days), reporting a 1.7-fold rise in urinary 6-sulfatoxymelatonin versus no change on placebo. So the tier is NOT 'animal-or-in-vitro-only' (a human RCT exists) and NOT 'no-credible-evidence' (a placebo-controlled human signal exists). It is 'promising-but-unproven' in the strict sense the label carries here: human data exists, efficacy is established for nothing. WHY 'UNPROVEN' IS DOING ALL THE WORK: (i) the endpoint was a melatonin METABOLITE, a surrogate — FDA's reviewers note the study 'did not evaluate sleep outcomes' at all, so a peptide sold for sleep has never been measured against sleep; (ii) FDA: 'we did not identify studies evaluating the use of these substances in patients with insomnia'; (iii) the publication did not specify blinding, and the reviewers flag short duration and small size; (iv) the authors' claim that subjects showed 'distinct positive dynamics of psycho-emotional and general physical condition in 83% of cases' came with no description of how either was assessed; (v) ROUTE MISMATCH — all three human studies used sublingual or parabulbar routes, while the route the nominations proposed is subcutaneous injection, for which FDA identified no human data at all; (vi) PROVENANCE — all three human studies trace to a single research lineage (Khavinson's group, which originated the peptide and authored the telomerase hypothesis), and the two night-shift studies (Ivko et al. 2021; Khavinson et al. 2021) share authors and population, so they may not be independent replications of one another. ClinicalTrials.gov holds zero registrations under any spelling, so there is no registered, results-reporting programme behind any of this.", "source": { "url": "https://link.springer.com/article/10.1134/S2079057021010380", "title": "AEDG Peptide Regulation of the Expression of Human Circadian Rhythm Genes upon Accelerated Aging of the Pineal Gland (Ivko, Linkova, Ilina, Sharova, Ruzhak)", "publisher": "Advances in Gerontology", "date": "2021-01-01" }, "verifiedAt": "2026-07-16" }, "fdaApproval": null, "fdaFindings": [ { "finding": "FDA staff propose not adding epitalon (free base) or epitalon acetate to the 503A Bulks List, ahead of the Pharmacy Compounding Advisory Committee meeting on 23-24 July 2026.", "note": "A staff proposal is not a final determination. The briefing document states: 'The FDA will not issue a final determination on the issues at hand until input from the advisory committee process has been considered and all reviews have been finalized.' FDA rests the proposal on four grounds: poor physicochemical characterisation, lack of data supporting safety in humans plus immunogenicity concern, lack of evidence of effectiveness for insomnia, and the availability of approved drugs for that condition.", "source": { "url": "https://www.fda.gov/media/193345/download", "title": "Epitalon-Related Bulk Drug Substances — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, July 23-24, 2026", "publisher": "FDA", "date": "2026-07-23", "quote": "Accordingly, we propose not adding epitalon (free base) or epitalon acetate to the 503A Bulks List." }, "verifiedAt": "2026-07-16" }, { "finding": "Neither epitalon (free base) nor epitalon acetate has a USP or NF drug substance monograph, and neither is a component of an FDA-approved drug.", "note": "The two statutory doors that close before the list is even reached. Under section 503A a bulk drug substance may be used in compounding if it appears in an applicable USP or NF monograph, if it is a component of an FDA-approved drug, or if it appears on the 503A Bulks List. This sentence forecloses the first two. It also disposes of the 'FDA-approved' claim directly: if any approved drug product contained epitalon, epitalon would be a component of an FDA-approved drug.", "source": { "url": "https://www.fda.gov/media/193345/download", "title": "Epitalon-Related Bulk Drug Substances — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, July 23-24, 2026", "publisher": "FDA", "date": "2026-07-23", "quote": "There is no applicable United States Pharmacopeia (USP) or National Formulary (NF) drug substance monograph for epitalon (free base) or its acetate form, and neither is a component of an FDA-approved drug." }, "verifiedAt": "2026-07-16" }, { "finding": "FDA evaluated epitalon ONLY for insomnia. The uses it is actually marketed for — anti-aging, longevity, lengthening telomeres, prevention of age-related disease — were not evaluated, because the nominations did not include sufficient information for FDA to evaluate them.", "note": "AN EVIDENTIARY VACUUM, NOT A REGULATORY LOOPHOLE — and the mismatch is the whole story of this compound. The market sells epitalon as a longevity drug; FDA assessed it as a sleep drug, because insomnia is the only proposed use anyone submitted enough information to support. 'FDA did not evaluate the longevity claims' does not mean the longevity claims survived scrutiny; it means nobody brought evidence to be scrutinised. Per the BPC-157 briefing's footnote 3, inclusion on the 503A Bulks List may not be limited to a specific use, so a 'do not add' outcome bars the substance for ALL indications regardless of which one FDA examined.", "source": { "url": "https://www.fda.gov/media/193345/download", "title": "Epitalon-Related Bulk Drug Substances — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, July 23-24, 2026", "publisher": "FDA", "date": "2026-07-23" }, "verifiedAt": "2026-07-16" }, { "finding": "FDA found no clinical data supporting the safety of epitalon in humans, and identified no human safety data at all for the subcutaneous route the nominations proposed.", "note": "Reconcile this with the evidence note rather than reading it as a contradiction: three studies administered epitalon to humans, but none was a safety study and none used the subcutaneous route. 'Human exposure has occurred' and 'human safety data exist' are different claims.", "source": { "url": "https://www.fda.gov/media/193345/download", "title": "Epitalon-Related Bulk Drug Substances — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, July 23-24, 2026", "publisher": "FDA", "date": "2026-07-23", "quote": "we conclude that there are no clinical data to support the safety of epitalon (free base) or epitalon acetate when used in humans" }, "verifiedAt": "2026-07-16" }, { "finding": "Epitalon held an FDA orphan drug designation for retinitis pigmentosa granted 2010-09-02; the designation was withdrawn/revoked on 2016-01-06.", "note": "Recorded because vendors cite the designation as quasi-approval. ORPHAN DESIGNATION IS NOT APPROVAL — it is an incentive status for developing a drug for a rare disease, granted before efficacy is shown. This one was for an eye disease, delivered by parabulbar injection, and it no longer exists. There is no FDA-approved epitalon product, which is why this record carries no fdaApproval field. FDA's document does not state the reason for the revocation and neither do we.", "source": { "url": "https://www.fda.gov/media/193345/download", "title": "Epitalon-Related Bulk Drug Substances — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, July 23-24, 2026", "publisher": "FDA", "date": "2026-07-23" }, "verifiedAt": "2026-07-16" }, { "finding": "FDA could not establish historical use in compounding: no outsourcing facility has reported compounding epitalon to FDA, and FDA could not identify any pharmacy that compounds it.", "note": "FDA notes wellness clinics that market epitalon state they obtain it from a compounding pharmacy, yet FDA could locate none. It found the substance sold online in vials, capsules and an oral spray, several vendors labelling it 'research use only'. The one documented compounding instance FDA cites is a criminal matter: a Nicholasville, Kentucky pharmacy and its owner pleaded guilty to unlawful distribution, having compounded and distributed epitalon-containing products between 2018-10-25 and 2020-04-01. Note the pattern this site keeps finding: category status is neither the safety line nor the criminal line. The Watkins indictment (D. Utah, 1:26-cr-00015, 2026-04-01) charges misbranding under 352(b), which is why Category 1 substances sit in the same indictment as substances that were never listed at all. Sourcing and labeling are the line.", "source": { "url": "https://www.fda.gov/media/193345/download", "title": "Epitalon-Related Bulk Drug Substances — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, July 23-24, 2026", "publisher": "FDA", "date": "2026-07-23" }, "verifiedAt": "2026-07-16" }, { "finding": "FDA found no pharmacokinetic data whatsoever for either epitalon substance — nothing on absorption, distribution, metabolism or elimination in humans or animals.", "note": "Eight words, and they undercut the entire marketing category. Pharmacokinetics is the most basic characterisation a drug receives — it is what converts a substance into a regimen. With no PK data, nothing is known about what happens to epitalon after it enters a person: not its half-life, not its bioavailability by any route, not whether an intact tetrapeptide survives to reach the pineal gland at all. Every cycling schedule sold online is therefore constructed on no measured human pharmacokinetics. Note how this interacts with the route mismatch elsewhere in this record: the three human studies used sublingual and parabulbar routes, and without PK there is no basis even to extrapolate from those routes to the subcutaneous one that is sold.", "source": { "url": "https://www.fda.gov/media/193345/download", "title": "Epitalon-Related Bulk Drug Substances — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, July 23-24, 2026", "publisher": "FDA", "date": "2026-07-23", "quote": "No pharmacokinetic data were found for epitalon (free base) or epitalon acetate." }, "verifiedAt": "2026-07-16" }, { "finding": "FDA searched its adverse-event databases and found zero reports for epitalon: no FAERS reports through 2025-12-08, and no cases in the Human Foods Complaint System through 2025-12-05.", "note": "READ THIS BACKWARDS FROM HOW VENDORS READ IT. Zero adverse-event reports is not a safety finding; it is a reporting finding, and FDA says so in its own footnotes. Three mechanisms explain the zero without any reference to whether epitalon harms people: (i) FAERS reporting is voluntary — 'FDA does not receive all adverse event reports that may potentially occur with a product, especially for compounded products'; (ii) FDA states that compounders under section 503A 'generally do not report adverse events to FDA', and that unless a report is submitted the Agency 'may not be aware' of events; (iii) a substance sold in vials labelled for research has no reporting pathway at all, and a buyer who is injecting something they obtained online is poorly placed to file with FDA and may not know they can. FDA's own conclusion is the limiting one: it 'cannot make definitive conclusions regarding the safety of epitalon based on FAERS data alone'. An empty surveillance database on a substance nobody surveils is not evidence of anything, in either direction.", "source": { "url": "https://www.fda.gov/media/193345/download", "title": "Epitalon-Related Bulk Drug Substances — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, July 23-24, 2026", "publisher": "FDA", "date": "2026-07-23", "quote": "A search of HFCS was conducted for AEs associated with epitalon through December 5, 2025, and retrieved no cases." }, "verifiedAt": "2026-07-16" }, { "finding": "No epitalon product is approved anywhere FDA looked: not in the United States, and not in Canada, Australia, the United Kingdom, Belgium, Ireland, France, Norway, Germany, Spain or Italy. It is recognised in neither the European nor the Japanese Pharmacopeia.", "note": "Recorded because the 'approved in Russia / used in Europe for decades' claim is a fixture of epitalon marketing, and because a reader checking one jurisdiction deserves the whole set in one place. FDA also states there are no epitalon products authorised for use in the European Union by the European Medicines Agency. Two further absences from the same document compound this: there is no USP or NF drug substance monograph for epitalon (free base) or its acetate form, and neither is a component of an FDA-approved drug. Those two facts are not trivia — under section 503A a bulk drug substance qualifies for compounding by appearing in a USP/NF monograph, by being a component of an approved drug, or by appearing on the 503A Bulks List. Epitalon satisfies none of the three. Beware the epithalamin equivocation here as well: any foreign-approval claim that rests on the animal-extract substance is a claim about a different substance (see moleculeNote).", "source": { "url": "https://www.fda.gov/media/193345/download", "title": "Epitalon-Related Bulk Drug Substances — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, July 23-24, 2026", "publisher": "FDA", "date": "2026-07-23", "quote": "There are no approved products containing epitalon in Canada, Australia, the United Kingdom, Belgium, Ireland, France, Norway, Germany, Spain, and Italy." }, "verifiedAt": "2026-07-16" }, { "finding": "FDA concluded there is a lack of evidence supporting effectiveness of either epitalon substance for insomnia, and identified no study evaluating either substance in patients who have insomnia.", "note": "The precise shape of the gap, which is narrower and more damning than 'no evidence'. Human data exists; it is simply about the wrong thing, in the wrong people, by the wrong route. The one clinical study FDA retrieved measured a melatonin metabolite in HEALTHY night-shift women, not in patients with diagnosed insomnia, and FDA notes the study 'did not evaluate sleep outcomes' and 'did not discuss clinical applicability of study results or potential therapeutic effect for insomnia or other sleep disorders'. FDA's reviewers name the inferential leap explicitly: 'The potential therapeutic effect of changes in melatonin levels induced by these substances is unclear without a corresponding evaluation of clinical outcomes.' A surrogate moved. Whether anyone slept better was never measured.", "source": { "url": "https://www.fda.gov/media/193345/download", "title": "Epitalon-Related Bulk Drug Substances — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, July 23-24, 2026", "publisher": "FDA", "date": "2026-07-23", "quote": "we did not identify studies evaluating the use of these substances in patients with insomnia, particularly when administered via the proposed SC ROA" }, "verifiedAt": "2026-07-16" }, { "finding": "The 'no side effects' claim commonly cited for epitalon traces to a conference abstract FDA could not evaluate — it was published in Russian, and reported no route, no duration, no subject count and no method of collecting safety data.", "note": "Follow the citation and it evaporates. The Korkushko et al. 2007 abstract states that pineal gland preparations (epitalon and epithalamin) have 'no side effects' in elderly people — and that sentence, with nothing behind it, is a load-bearing beam of epitalon's safety reputation. FDA searched multiple databases and could not locate the full article in English. So the claim cannot be checked: no denominator, no follow-up period, no ascertainment method. It also lumps epitalon together with epithalamin, the animal-extract substance FDA treats as different. Note the asymmetry that makes this citation worthless rather than merely weak: an abstract too thin to describe its own methods is exactly the study least able to detect a side effect, and 'nothing was found' by a method that could not find anything is not a finding.", "source": { "url": "https://www.fda.gov/media/193345/download", "title": "Epitalon-Related Bulk Drug Substances — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, July 23-24, 2026", "publisher": "FDA", "date": "2026-07-23", "quote": "details such as ROA, dosing information, duration of administration, number of subjects and demographics, and methods of safety data collection were not provided in the abstract" }, "verifiedAt": "2026-07-16" } ], "safetySignals": [ { "signal": "The telomerase mechanism epitalon is marketed FOR is the same mechanism FDA flags as a carcinogenicity concern under chronic continuous use.", "note": "THE SINGLE MOST INVERTED CLAIM IN THIS COMPOUND'S MARKETING. Vendor and clinic pages sell telomerase activation as the benefit — 'the fountain of youth', per FDA's own survey of those sites. FDA's reviewers take the same reported mechanism and read it as a hazard: cells that evade senescence are the definition of cancerous. FDA also cites literature associating long telomeres with INCREASED malignancy risk (McNally et al. 2019). Attribute carefully, in both directions: the telomerase and telomere-elongation findings come from in-vitro work in cultured human fetal lung fibroblasts (Khavinson et al. 2003; Malinin and Khavinson 2005) — cell culture, not people — so neither the benefit claim nor the cancer concern is established in humans. The honest statement is that the mechanism is unproven and its DIRECTION of effect in a living human is unknown, and 'unknown' is not the same as 'safe'. FDA notes the dependence on regimen: the mouse studies reporting reduced tumour incidence used INTERMITTENT exposure, whereas the concern is raised for CONTINUOUS lifelong exposure — which is closer to how the substance is marketed for use.", "source": { "url": "https://www.fda.gov/media/193345/download", "title": "Epitalon-Related Bulk Drug Substances — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, July 23-24, 2026", "publisher": "FDA", "date": "2026-07-23", "quote": "reports that epitalon can activate telomerase and lengthen telomeres raise concerns that continuous exposure to epitalon through the lifespan could enable cells to evade senescence and become cancerous" }, "verifiedAt": "2026-07-16" }, { "signal": "No 2-year carcinogenicity study of epitalon exists, and FDA states the existing mouse tumour studies are too short to detect carcinogenic potential.", "note": "The three mouse studies most often cited as evidence that epitalon PREVENTS cancer (Anisimov et al. 2001b, 2002b, 2003) were all conducted by one research group, all used a single fixed dose (so no dose-response could be assessed), and all used female mice only. FDA notes total exposure in those studies fell far short of the 12+ months needed for sensitivity, citing Haseman et al. 2001 that 12-18 month rodent treatment already corresponds to evaluating cancer in 30-50 year old humans and markedly reduces detection sensitivity. FDA identified no 2-year carcinogenicity study and no data sufficient for a weight-of-evidence analysis. Absence of a tumour finding in an underpowered short study is not evidence of safety.", "source": { "url": "https://www.fda.gov/media/193345/download", "title": "Epitalon-Related Bulk Drug Substances — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, July 23-24, 2026", "publisher": "FDA", "date": "2026-07-23" }, "verifiedAt": "2026-07-16" }, { "signal": "FDA raised an immunogenicity concern specific to the injectable route the nominations proposed, and concluded available data are insufficient to rule the risk out.", "note": "Grounded in aggregation: peptides as short as two amino acids can aggregate, and aggregates are a risk factor for immunogenicity and anti-drug antibody formation. FDA notes injectable routes may present a particular (systemic rather than local) immunogenicity risk, and that peptide stability and immunogenic properties are highly sensitive to the manufacturing process and quality of the finished product — which is exactly the variable an unregulated supply chain does not control. No clinical study has assessed immunogenicity or aggregation of either epitalon substance.", "source": { "url": "https://www.fda.gov/media/193345/download", "title": "Epitalon-Related Bulk Drug Substances — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, July 23-24, 2026", "publisher": "FDA", "date": "2026-07-23" }, "verifiedAt": "2026-07-16" }, { "signal": "FDA identified no pharmacokinetic data and no clinical safety study for either epitalon substance, and states there is a lack of important information about subcutaneous use including whether it would cause harm in humans.", "note": "The honest summary of epitalon's safety record, in FDA's own words: the question is open. Not answered reassuringly, not answered alarmingly — unasked. Assembling the absences from across this document: no pharmacokinetic data of any kind; no clinical study assessing safety; no study assessing immunogenicity or aggregation; no 2-year carcinogenicity study; zero adverse-event reports from surveillance systems that a research-labelled online product never reaches. Each is separately sourced above. The failure mode this record exists to prevent is reading that stack of absences as a clean bill of health. Nothing here has been tested and passed. It has not been tested.", "source": { "url": "https://www.fda.gov/media/193345/download", "title": "Epitalon-Related Bulk Drug Substances — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, July 23-24, 2026", "publisher": "FDA", "date": "2026-07-23", "quote": "there is a lack of important information regarding the use of these substances administered subcutaneously, including whether the drug would cause harm if administered to humans" }, "verifiedAt": "2026-07-16" }, { "signal": "FDA could not adequately characterise the substance physicochemically: no Certificate of Analysis for epitalon (free base) existed in the nomination packages, and no bioburden or endotoxin testing was mentioned for epitalon acetate.", "note": "Unglamorous and arguably the most practically important signal here. Endotoxin and bioburden are the tests that catch a contaminated injectable; FDA notes the proposed subcutaneous route is generally associated with increased risk from impurities. Poor characterisation is the FIRST of the four grounds FDA gives for proposing not to add these substances — before efficacy. If the identity and purity of the powder are unestablished, every downstream claim about what it does is unanchored, whichever direction it points.", "source": { "url": "https://www.fda.gov/media/193345/download", "title": "Epitalon-Related Bulk Drug Substances — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, July 23-24, 2026", "publisher": "FDA", "date": "2026-07-23" }, "verifiedAt": "2026-07-16" } ], "faqs": [ { "question": "Is epitalon legal in 2026?", "answer": "Epitalon is not eligible for use in pharmacy compounding under section 503A. A bulk drug substance qualifies only by appearing in a USP or NF monograph, by being a component of an FDA-approved drug, or by appearing on FDA's 503A bulks list, and FDA's briefing document for the July 2026 advisory committee meeting states that epitalon meets none of the three: there is no USP or NF monograph for epitalon (free base) or its acetate form, neither is a component of an FDA-approved drug, and FDA staff propose not adding either to the bulks list. Its absence from the bulks list is not permission — the two nominations that would have placed it there were withdrawn by the nominators. Separately, a category or list status is not a statement about whether possessing or selling a substance is lawful: the compounding pharmacy FDA cites in connection with epitalon pleaded guilty to unlawful distribution over conduct in 2018-2020, when epitalon was in no category at all.", "source": { "url": "https://www.fda.gov/media/193345/download", "title": "Epitalon-Related Bulk Drug Substances — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, July 23-24, 2026", "publisher": "FDA", "date": "2026-07-23" }, "verifiedAt": "2026-07-16" }, { "question": "Did epitalon become legal again when FDA removed it from the nomination list?", "answer": "No. Epitalon left FDA's 503A nomination track because both nominations for it — from Wells Pharmacy Network and from LDT Health Solutions on behalf of the International Peptide Society — were withdrawn by the nominators, not because FDA evaluated it favourably. Withdrawal moves a substance sideways, not toward legality: epitalon did not enter Category 1, it is not on the 503A bulks list, and it remains ineligible for compounding. FDA's own posture shows withdrawal ended nothing — the Agency is evaluating epitalon (free base) and epitalon acetate on its own initiative despite the withdrawals, considered the withdrawn nomination materials as part of that evaluation, and its staff proposed not to add either substance to the list ahead of the advisory committee meeting of 23-24 July 2026.", "source": { "url": "https://www.fda.gov/media/193345/download", "title": "Epitalon-Related Bulk Drug Substances — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, July 23-24, 2026", "publisher": "FDA", "date": "2026-07-23" }, "verifiedAt": "2026-07-16" }, { "question": "Did FDA approve epitalon?", "answer": "No. There is no FDA-approved drug product containing epitalon, and FDA's briefing document for the July 2026 advisory committee meeting states that neither epitalon (free base) nor epitalon acetate is a component of an FDA-approved drug. FDA also found no approved epitalon products in Canada, Australia, the United Kingdom, Belgium, Ireland, France, Norway, Germany, Spain or Italy, none authorised in the European Union by the European Medicines Agency, and no recognition in the European or Japanese Pharmacopeia. Epitalon did hold an FDA orphan drug designation for retinitis pigmentosa granted 2010-09-02, and that designation was withdrawn or revoked on 2016-01-06 — orphan designation is an incentive status granted before efficacy is shown, it is not approval, and this one no longer exists.", "source": { "url": "https://www.fda.gov/media/193345/download", "title": "Epitalon-Related Bulk Drug Substances — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, July 23-24, 2026", "publisher": "FDA", "date": "2026-07-23" }, "verifiedAt": "2026-07-16" }, { "question": "Is there any human evidence that epitalon works?", "answer": "There is human data, but it establishes efficacy for nothing. FDA's literature search found three published studies in which epitalon was administered to humans — two in night-shift workers by the sublingual route and one by parabulbar injection in patients with congenital retinitis pigmentosa. FDA describes one of them (Ivko et al. 2021) as a randomised, placebo-controlled study in healthy women aged 40-50 in which researchers reported urinary excretion of a melatonin metabolite rose 1.7-fold against no change on placebo. FDA's reviewers note that study did not evaluate sleep outcomes, did not specify blinding, and was short and small, and that FDA 'did not identify studies evaluating the use of these substances in patients with insomnia'. No human study used the subcutaneous route the nominations proposed, and ClinicalTrials.gov holds no registrations under epitalon, epithalon or AEDG (queried 2026-07-16). No human study of any kind has tested the anti-aging or longevity uses epitalon is marketed for.", "source": { "url": "https://www.fda.gov/media/193345/download", "title": "Epitalon-Related Bulk Drug Substances — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, July 23-24, 2026", "publisher": "FDA", "date": "2026-07-23" }, "verifiedAt": "2026-07-16" }, { "question": "Can I get epitalon from a compounding pharmacy?", "answer": "FDA could not find a single pharmacy that compounds epitalon. Its briefing document for the July 2026 advisory committee meeting records that no outsourcing facility has reported compounding epitalon-containing drug products to FDA, and that although wellness clinics marketing epitalon state they obtain it from a compounding pharmacy, FDA was unable to identify any pharmacy that compounds any form of it. FDA concluded that available data are too limited for it to understand the historical use of any form of epitalon in compounded drug products. What FDA did find was epitalon sold online in vials, capsules and an oral spray, with several sites stating the product is intended for research use only. The one documented instance of epitalon compounding FDA cites is a criminal matter: a Nicholasville, Kentucky pharmacy and its owner pleaded guilty to unlawful distribution after compounding and distributing epitalon-containing products between 2018-10-25 and 2020-04-01.", "source": { "url": "https://www.fda.gov/media/193345/download", "title": "Epitalon-Related Bulk Drug Substances — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, July 23-24, 2026", "publisher": "FDA", "date": "2026-07-23" }, "verifiedAt": "2026-07-16" }, { "question": "Is epitalon safe?", "answer": "Nobody knows, and FDA says so: its briefing document for the July 2026 advisory committee meeting concludes there are no clinical data to support the safety of epitalon (free base) or epitalon acetate when used in humans, and that there is a lack of important information about subcutaneous use 'including whether the drug would cause harm if administered to humans'. FDA found no pharmacokinetic data for either substance, no clinical study assessing their safety, and no study assessing immunogenicity or aggregation. Searches of FDA's adverse-event systems returned zero reports, which is not evidence of safety: FDA notes that reporting is voluntary, that compounders under section 503A generally do not report adverse events to the Agency, and that it 'cannot make definitive conclusions regarding the safety of epitalon based on FAERS data alone'. FDA raised two specific unresolved concerns — immunogenicity from peptide aggregation and impurities by the injectable route, and carcinogenic potential. On the second, FDA's reviewers join two independent premises: that epitalon has been reported to activate telomerase and lengthen telomeres — reported in cultured human fetal lung fibroblasts (Khavinson et al. 2003; Malinin and Khavinson 2005), cell culture rather than people — and, separately from the epitalon literature, that longer telomeres are generally associated with increased risk for cancer (McNally et al. 2019). From those, FDA reasons that continuous exposure across the lifespan 'could enable cells to evade senescence and become cancerous'. There is no 2-year carcinogenicity study of epitalon.", "source": { "url": "https://www.fda.gov/media/193345/download", "title": "Epitalon-Related Bulk Drug Substances — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, July 23-24, 2026", "publisher": "FDA", "date": "2026-07-23" }, "verifiedAt": "2026-07-16" }, { "question": "Does epitalon lengthen telomeres?", "answer": "Not demonstrated in humans. FDA's briefing document for the July 2026 advisory committee meeting reports that epitalon has been shown to activate telomerase and lengthen telomeres, but the underlying work FDA cites (Khavinson et al. 2003; Malinin and Khavinson 2005) was conducted in cultured human fetal lung fibroblasts — cell culture, not people. No human study has measured telomere length after epitalon administration. FDA does not treat that reported mechanism as a benefit: its reviewers state that reports epitalon can activate telomerase and lengthen telomeres 'raise concerns that continuous exposure to epitalon through the lifespan could enable cells to evade senescence and become cancerous', and note that longer telomeres are generally associated with increased risk for cancer. The same in-vitro finding that vendor sites sell as anti-aging is the finding FDA flags as a carcinogenicity concern, and neither reading is established in humans.", "source": { "url": "https://www.fda.gov/media/193345/download", "title": "Epitalon-Related Bulk Drug Substances — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, July 23-24, 2026", "publisher": "FDA", "date": "2026-07-23" }, "verifiedAt": "2026-07-16" } ] }, { "slug": "exenatide", "name": "Exenatide", "aliases": [ "Byetta", "Bydureon", "Bydureon Pen", "Bydureon BCise", "exenatide synthetic", "exendin-4", "ITCA 650" ], "url": "https://peptides101.com/compounds/exenatide", "moleculeNote": "A glucagon-like peptide-1 (GLP-1) receptor agonist. The FDA-approved labeling describes it verbatim as follows: 'Exenatide is a synthetic peptide, GLP-1 receptor agonist, that was originally identified in the lizard Heloderma suspectum. Exenatide is a 39-amino acid peptide amide.' The label prints the complete amino acid sequence, which means the identity of anything sold under this name is checkable against a public FDA document rather than against a vendor's certificate of analysis. TWO DISAMBIGUATIONS THAT CARRY REAL CONSEQUENCES. (1) FORMULATION. Immediate-release exenatide injection and exenatide extended-release are not interchangeable records: the extended-release products carried a boxed warning for risk of thyroid C-cell tumors and the immediate-release labeling carries no boxed warning at all, and the extended-release products are the ones whose approvals were withdrawn. Same molecule, different label, different regulatory fate. (2) NAMING. FDA's labeling does not use the name 'exendin-4' anywhere — it says 'synthetic peptide … originally identified in the lizard Heloderma suspectum'. 'Exendin-4' is listed in the aliases above because material is sold under that name, not because an FDA document equates the two.", "quickAnswer": "Exenatide is an FDA-approved GLP-1 receptor agonist, first approved on 28 April 2005 as a new molecular entity under NDA 021773 (Byetta), and its sole approved indication is 'as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus' — no exenatide product has ever held an FDA indication for weight loss. FDA has since withdrawn approval of every branded exenatide application at the applicants' own request because the products were no longer marketed — Byetta (NDA 021773), Bydureon and Bydureon Pen (NDA 022200) and Bydureon BCise (NDA 209210), effective 3 September 2025 — leaving a generic exenatide injection (ANDA 206697, Amneal Pharmaceuticals, approved 19 November 2024). Drugs@FDA also lists BYETTA under NDA 021919 as 'Prescription', so this is not the only non-discontinued exenatide product on the database.", "fdaStatus": { "value": "approved", "note": "Approved, and the reason that word is right here is narrower than it looks. Every BRANDED exenatide application has had its approval withdrawn — see fdaFindings. What remains is a generic: exenatide injection under ANDA 206697 (Amneal Pharmaceuticals), approved 2024-11-19, which Drugs@FDA lists with marketing status 'Prescription' and for which FDA hosts a current approved label with an SPL effectiveTime of 2026-05-27. The vocabulary's own explainer for `approval-withdrawn` says 'No approved product is on the market'; that is not this compound's situation, so the badge would have been false. ONE DISCREPANCY, RECORDED RATHER THAN RESOLVED. Drugs@FDA also lists NDA 021919 (Byetta, Amylin, approved 2009-10-30 as a Type 6 New Indication) with marketing status 'Prescription'. That application appears in neither Federal Register withdrawal notice, and a full-text Federal Register search for 'NDA 021919' returns nothing. Whether that status is live or stale is not something the documents settle, so this record does not settle it either; the `approved` value does not depend on it, because the Amneal ANDA carries it independently.", "source": { "url": "https://www.accessdata.fda.gov/spl/data/2141c3ca-074a-4098-85da-1ef78ec4d4dc/2141c3ca-074a-4098-85da-1ef78ec4d4dc.xml", "title": "EXENATIDE injection, for subcutaneous use — Prescribing Information (SPL, ANDA 206697)", "publisher": "FDA", "date": "2026-05-27", "quote": "Exenatide injection is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus." }, "verifiedAt": "2026-08-02" }, "compoundingStatus": null, "evidence": { "tier": "proven-in-humans", "humanAdministrationChecked": true, "note": "QUOTE HANDLING: the label names the milligram-equivalent strengths of each arm and their administration frequency. They are elided above with ellipses under this site's no-dosing policy — a dose-to-outcome mapping is the actionable part for someone self-administering an unapproved vial. Nothing else in the quote is altered, and no finding below depends on the elided figures. ADMINISTRATION CHECK RUN, NOT ASSUMED. Section 14 of the current FDA-approved labeling was opened and read on 2026-08-02. Exenatide was injected subcutaneously into randomised human subjects and compared against placebo injected on the same schedule — it was not measured as an endogenous biomarker, which is the trap that reduces MOTS-c and TB-500 from an apparent five human RCTs to an actual zero. THE TRIALS, NAMED AS PRECISELY AS THE DOCUMENTS ALLOW. For the approved glycemic indication: a randomised, double-blind, placebo-controlled monotherapy trial of 24 weeks' duration (intent-to-treat n=232 across three arms); three randomised, double-blind, placebo-controlled trials of 30 weeks' duration in patients inadequately controlled on metformin, a sulfonylurea, or both (1,446 patients randomised); and a placebo-controlled trial of 16 weeks' duration adding exenatide to an existing thiazolidinedione with or without metformin (n=233). HONEST LIMITATION: the label does not carry NCT identifiers for these trials, which predate registration practice, so they are named by the label's own description and cannot be independently pulled from a registry by number. ONE TRIAL IS NCT-IDENTIFIED AND WAS CHECKED DIRECTLY. EXSCEL (NCT01144338) was opened on 2026-08-02 via the ClinicalTrials.gov API: study type INTERVENTIONAL, intervention type DRUG, exenatide once weekly versus placebo, Phase 3, enrolment 14,752 ACTUAL, lead sponsor AstraZeneca, status COMPLETED (primary completion 2017-04-21, completion 2017-04-24), hasResults true. SCOPE, AND IT IS THE WHOLE POINT. This tier attaches to the approved indication — glycemic control in adults with type 2 diabetes — and to the approved products. It does not travel to weight loss, for which no exenatide product has ever held an FDA indication; it does not travel to the neurodegenerative-disease uses exenatide is discussed for in the research literature; and it does not travel to unapproved material sold under this name or under 'exendin-4'. EXSCEL is also a caution against inflating the tier: a 14,752-patient cardiovascular outcomes trial ran, and FDA-approved labeling reports it did not meet the superiority test.", "source": { "url": "https://www.accessdata.fda.gov/spl/data/2141c3ca-074a-4098-85da-1ef78ec4d4dc/2141c3ca-074a-4098-85da-1ef78ec4d4dc.xml", "title": "EXENATIDE injection, for subcutaneous use — Prescribing Information (SPL, ANDA 206697)", "publisher": "FDA", "date": "2026-05-27", "quote": "In a randomized, double-blind, placebo-controlled trial of 24 weeks duration, exenatide … or placebo BID was used as monotherapy in patients with entry HbA1c ranging from 6.5% to 10%. … Exenatide or placebo was injected subcutaneously before the morning and evening meals. … Compared to placebo, exenatide … resulted in statistically significant reductions in HbA1c from baseline at Week 24." }, "verifiedAt": "2026-08-02" }, "fdaApproval": { "applicationNumber": "ANDA 206697 (exenatide injection, Amneal Pharmaceuticals) — approved 2024-11-19 and the exenatide application whose label is cited here. Drugs@FDA also lists BYETTA under NDA 021919 with marketing status 'Prescription', so this is not the only non-discontinued exenatide record. Approval of NDA 021773 (Byetta), NDA 022200 (Bydureon, Bydureon Pen) and NDA 209210 (Bydureon BCise) has been withdrawn.", "brandName": "Byetta, Bydureon, Bydureon Pen, Bydureon BCise — all withdrawn", "approvedIndication": "Exenatide injection is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. Limitations of Use: Exenatide injection contains exenatide. Co-administration with other exenatide-containing products is not recommended.", "discontinued": false, "discontinuedNote": "`discontinued` is false because an approved exenatide product is marketed — but the brands are gone, and the manner of their going is the record. FDA withdrew approval of Byetta (NDA 021773), Bydureon and Bydureon Pen (NDA 022200) and Bydureon BCise (NDA 209210) effective 2025-09-03. The Federal Register notice states the applicants informed FDA the products were no longer marketed and requested withdrawal under 21 CFR 314.150(c), and that they waived their opportunity for a hearing. READ WHAT THE NOTICE DOES AND DOES NOT SAY. It gives one stated reason: no longer marketed. It records no safety or effectiveness determination. This site does not read that silence as an endorsement — a withdrawal at the sponsor's request is the absence of a finding, not a finding of absence — and it does not read it as a safety withdrawal either. The notice also states withdrawal under this section is 'without prejudice to refiling'.", "source": { "url": "https://www.accessdata.fda.gov/spl/data/2141c3ca-074a-4098-85da-1ef78ec4d4dc/2141c3ca-074a-4098-85da-1ef78ec4d4dc.xml", "title": "EXENATIDE injection, for subcutaneous use — Prescribing Information (SPL, ANDA 206697)", "publisher": "FDA", "date": "2026-05-27", "quote": "Exenatide injection is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus." }, "verifiedAt": "2026-08-02" }, "fdaFindings": [ { "finding": "FDA withdrew approval of Byetta (NDA 021773), Bydureon and Bydureon Pen (NDA 022200) and Bydureon BCise (NDA 209210) effective September 3, 2025. The applicants informed FDA that the drug products were no longer marketed and requested that FDA withdraw approval under 21 CFR 314.150(c), waiving their opportunity for a hearing.", "note": "The single most load-bearing document on this record, and it is not what the secondary coverage says. 'Byetta was discontinued' describes a commercial decision. This is a regulatory act: the applications no longer exist as approvals. FDA's notice states that 'Introduction or delivery for introduction into interstate commerce of products listed in table 1 without an approved NDA violates sections 505(a) and 301(d) of the Federal Food, Drug, and Cosmetic Act', while permitting inventory on hand at the effective date to be dispensed until depleted or expired. Verified by reading table 1 of the raw Federal Register text line by line on 2026-08-02; all three application numbers are present. FDA's own typo is in the source, which prints 'Bydrueon BCise'.", "source": { "url": "https://www.federalregister.gov/documents/2025/08/04/2025-14683/teva-branded-pharmaceutical-products-randd-inc-et-al-withdrawal-of-approval-of-39-new-drug", "title": "Teva Branded Pharmaceutical Products R&D, Inc., et al.; Withdrawal of Approval of 39 New Drug Applications (90 FR 36440)", "publisher": "FDA", "date": "2025-08-04", "quote": "The applicants listed in table 1 have informed FDA that these drug products are no longer marketed and have requested that FDA withdraw approval of the applications under the process in Sec. 314.150(c) (21 CFR 314.150(c)). … Therefore, approval of the applications listed in table 1, and all amendments and supplements thereto, is hereby withdrawn as of September 3, 2025." }, "verifiedAt": "2026-08-02" }, { "finding": "FDA listed NDA 022200 (Bydureon, Bydureon Pen) and NDA 209210 (Bydureon BCise) a SECOND time, in a later withdrawal notice stating approval is withdrawn as of April 8, 2026. The same two applications appear in the earlier notice withdrawing approval as of September 3, 2025.", "note": "Recorded because it was found, not because it is explained. Both Federal Register notices were fetched as raw text and searched on 2026-08-02: NDA 022200 and NDA 209210 appear in table 1 of each, with different effective dates and slightly different applicant address blocks. Byetta (NDA 021773) appears only in the 2025 notice. This record does not guess at the cause — a duplicate listing, a re-issuance, or something else — and it does not average the dates. Anyone citing a single withdrawal date for Bydureon should know a second notice exists, because a citation that names one date without knowing about the other is a citation that has not read the documents.", "source": { "url": "https://www.federalregister.gov/documents/2026/03/09/2026-04546/aspen-global-inc-co-lachman-consultant-services-inc-et-al-withdrawal-of-approval-of-46-new-drug", "title": "Aspen Global Inc. c/o Lachman Consultant Services, Inc., et al.; Withdrawal of Approval of 46 New Drug Applications (91 FR 11321)", "publisher": "FDA", "date": "2026-03-09", "quote": "Therefore, approval of the applications listed in table 1, and all amendments and supplements thereto, is hereby withdrawn as of April 8, 2026." }, "verifiedAt": "2026-08-02" }, { "finding": "FDA issued an order refusing to approve NDA 209053 for ITCA 650 (exenatide in DUROS device), a subdermally implanted osmotic mini-pump delivering exenatide, finding that Intarcia Therapeutics had not demonstrated the product is safe for its intended use.", "note": "A full adjudicated refusal, which is rare and far stronger than a complete response letter. The procedural history in FDA's own notice: NDA submitted 2016-11-21 with three phase 3 trials (CLP-103, CLP-105 and CLP-107, the latter also called FREEDOM, a cardiovascular outcome trial); complete response 2017-09-21; resubmission 2019-09-19; second complete response 2020-03-09; hearing request 2021-03-16; notice of opportunity for a hearing 2021-09-02 (86 FR 49334); final decision 2024-08-23. READ THE SCOPE PRECISELY, because it is easy to over-read in both directions. FDA refused a specific DRUG-DEVICE COMBINATION, not the active ingredient — exenatide by injection was already approved and still is. But the deficiencies were not purely mechanical: FDA's notice records concerns about acute kidney injury, an unresolved cardiovascular risk signal, and drug-delivery variability that 'compare unfavorably to approved products with a similar or identical active ingredient'.", "source": { "url": "https://www.federalregister.gov/documents/2024/08/23/2024-18898/final-decision-on-the-proposal-to-refuse-to-approve-a-new-drug-application-for-itca-650", "title": "Final Decision on the Proposal To Refuse To Approve a New Drug Application for ITCA 650 (89 FR 68168)", "publisher": "FDA", "date": "2024-08-23", "quote": "FDA finds that the record shows that the approval criteria set forth in section 505(d)(2) of the FD&C Act have not been met, as ITCA 650's risks outweigh its benefits; therefore, Intarcia has not demonstrated that ITCA 650 is safe for its intended use. Therefore, under section 505(d) of the FD&C Act, FDA hereby denies approval to Intarcia's NDA in its current form." }, "verifiedAt": "2026-08-02" }, { "finding": "In EXSCEL, the cardiovascular outcomes trial of exenatide extended-release in 14,752 adults with type 2 diabetes, FDA-approved labeling reported that exenatide extended-release did not increase the risk of major adverse cardiac events, meeting the pre-specified non-inferiority margin but not the superiority test.", "note": "The finding that separates exenatide from the GLP-1 halo, and it is FDA-approved wording rather than a critic's characterisation. Independently corroborated on 2026-08-02 against the posted results for NCT01144338 on ClinicalTrials.gov, which record the same hazard ratio of 0.91 with a 95% confidence interval of 0.832 to 1.004, a superiority p-value of 0.061 against the null hypothesis HR ≥ 1, and a non-inferiority p-value of less than 0.001 against a margin of 1.3. WHY THIS IS WORTH RECORDING: the confidence interval crosses 1.00, so the trial is consistent with no cardiovascular benefit. That is a materially different result from the class members that did establish cardiovascular indications, and it is the reason no exenatide product ever carried one. The trial is also the strongest evidence on this record that a large, well-conducted, completed programme is not the same thing as a positive one.", "source": { "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/209210s025lbl.pdf", "title": "BYDUREON BCISE (exenatide) extended-release injectable suspension — Highlights of Prescribing Information (NDA 209210, SUPPL-25)", "publisher": "FDA", "date": "2025-05-28", "quote": "BYDUREON did not increase the risk of MACE in adult patients with type 2 diabetes mellitus (HR: 0.91; 95% CI: 0.832, 1.004; P<0.001 for non-inferiority; P=0.06 for superiority)." }, "verifiedAt": "2026-08-02" }, { "finding": "Exenatide appears in none of Categories 1, 2 or 3 of FDA's list of bulk drug substances nominated for use in compounding under section 503A, updated 2026-05-14.", "note": "Recorded to close a misreading, not to assert a status — which is why this record carries no `compoundingStatus` field at all. Verified by fetching the PDF with a browser user-agent and text-extracting it locally on 2026-08-02: zero hits for 'xenatide', 'yetta' or 'ydureon' across all seven pages. This absence means something entirely different from BPC-157's absence. BPC-157 was nominated and left Category 2 when the nominators withdrew. Exenatide was never in this system: a 503A bulks nomination is a route for substances without an approved product, and exenatide has one on the market. Categorical silence here is neither permission nor a safety finding.", "source": { "url": "https://www.fda.gov/media/94155/download", "title": "Bulk Drug Substances Nominated for Use in Compounding Under Section 503A of the Federal Food, Drug, and Cosmetic Act", "publisher": "FDA", "date": "2026-05-14" }, "verifiedAt": "2026-08-02" }, { "finding": "Drugs@FDA records five applications containing exenatide. The original approval, NDA 021773 (Byetta), was approved 2005-04-28 as a Type 1 New Molecular Entity. The generic, ANDA 206697 (Amneal), was approved 2024-11-19 and is listed with marketing status 'Prescription'; both of its products carry therapeutic equivalence code AP and are flagged as reference standard.", "note": "The chronology is the story. FDA approved the generic on 2024-11-19, nine months before the brand it references lost its approval on 2025-09-03 — and Drugs@FDA now flags the GENERIC as the reference standard, the role the brand used to hold. A first-in-class originator exited and its copy became the benchmark. A METHOD NOTE THAT IS ALSO A WARNING. Searching openFDA by `openfda.generic_name` returns only two of these five applications, because the openFDA block is empty or partial on several exenatide records; the query in the source URL uses `products.active_ingredients.name`, which returns all five. A NOT_FOUND from the wrong field is an artifact of the query, not a fact about the database — the same mistake once produced a false 'sermorelin is not in Drugs@FDA' claim in this library. ON 'THE FIRST GLP-1': the 2005-04-28 Type 1 New Molecular Entity approval is primary and sourced. The first-in-class superlative is NOT asserted anywhere in this record, because no single FDA document read here states it. Running the same Drugs@FDA query for other GLP-1 receptor agonists returns later original approvals (liraglutide NDA 022341, 2010-01-25; semaglutide NDA 209637, 2017-12-05; tirzepatide NDA 215866, 2022-05-13), which is consistent with the claim but is a derivation, not a citation.", "source": { "url": "https://api.fda.gov/drug/drugsfda.json?search=products.active_ingredients.name:%22EXENATIDE%22&limit=20", "title": "Drugs@FDA — applications containing exenatide (openFDA drug/drugsfda)", "publisher": "FDA", "date": "2026-07-31" }, "verifiedAt": "2026-08-02" } ], "safetySignals": [ { "signal": "Boxed warning on the withdrawn extended-release products — risk of thyroid C-cell tumors. Exenatide extended-release causes an increased incidence in thyroid C-cell tumors at clinically relevant exposures in rats compared to controls. It is unknown whether exenatide extended-release causes thyroid C-cell tumors, including medullary thyroid carcinoma (MTC), in humans. Contraindicated in patients with a personal or family history of MTC or in patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2).", "note": "Recorded against the extended-release label specifically, and the scoping is the finding. This boxed warning is NOT on the immediate-release exenatide injection that remains on the market — that label carries no boxed warning at all, and no MTC or MEN 2 contraindication. Same active ingredient, different formulation, different highest-level FDA warning. Anyone reasoning 'exenatide has a thyroid boxed warning' or 'exenatide has no thyroid boxed warning' is half right and cannot tell which half without naming the product. The applications carrying this warning had their approvals withdrawn, so the label is archival — it is cited here because it is the primary document and it is still on accessdata.fda.gov.", "source": { "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/209210s025lbl.pdf", "title": "BYDUREON BCISE (exenatide) extended-release injectable suspension — Highlights of Prescribing Information (NDA 209210, SUPPL-25)", "publisher": "FDA", "date": "2025-05-28", "quote": "Exenatide extended-release causes an increased incidence in thyroid C-cell tumors at clinically relevant exposures in rats compared to controls. It is unknown whether BYDUREON BCISE causes thyroid C-cell tumors, including medullary thyroid carcinoma (MTC), in humans, as the human relevance of exenatide extended-release-induced rodent thyroid C-cell tumors has not been determined." }, "verifiedAt": "2026-08-02" }, { "signal": "Contraindication and labeled warning on the marketed immediate-release product — drug-induced immune-mediated thrombocytopenia. Serious bleeding, which may be fatal, from drug-induced immune-mediated thrombocytopenia has been reported with exenatide use. Exenatide injection is contraindicated in patients with a history of drug-induced immune-mediated thrombocytopenia from exenatide products.", "note": "The exenatide-specific signal, and the one least likely to be known by someone generalising from the GLP-1 class. It is a contraindication, not merely a precaution, and the label instructs discontinuation and avoidance of re-exposure. Note the wording of the contraindication: it is scoped to 'exenatide products' as a class, so a reaction on one exenatide product rules out the others — the kind of cross-product screening question that only exists because there is a label to ask it.", "source": { "url": "https://www.accessdata.fda.gov/spl/data/2141c3ca-074a-4098-85da-1ef78ec4d4dc/2141c3ca-074a-4098-85da-1ef78ec4d4dc.xml", "title": "EXENATIDE injection, for subcutaneous use — Prescribing Information (SPL, ANDA 206697)", "publisher": "FDA", "date": "2026-05-27", "quote": "A history of drug-induced immune-mediated thrombocytopenia from exenatide products. Serious bleeding, which may be fatal, from drug-induced immune-mediated thrombocytopenia has been reported with exenatide use." }, "verifiedAt": "2026-08-02" }, { "signal": "Labeled warnings and precautions on the marketed immediate-release product include acute pancreatitis, hypoglycemia with concomitant use of insulin secretagogues or insulin, acute kidney injury due to volume depletion, severe gastrointestinal adverse reactions, immunogenicity, hypersensitivity including anaphylaxis and angioedema, drug-induced immune-mediated thrombocytopenia, acute gallbladder disease, and pulmonary aspiration during general anesthesia or deep sedation. The label also instructs that an exenatide injection pen must never be shared between patients, even if the needle is changed.", "note": "Reproduced because 'well-tolerated' does heavy lifting in how this class is sold. The label lists as most common, at 5% or greater and more frequent than placebo in clinical trials: nausea, hypoglycemia, vomiting, diarrhea, feeling jittery, dizziness, headache, dyspepsia, constipation and asthenia. The label also states exenatide is not recommended in patients with severe gastroparesis, and that patients may develop antibodies to exenatide — with the labeled consequence being worsening or failure to achieve target glycemic control, which is a loss-of-effect signal rather than a toxicity one.", "source": { "url": "https://www.accessdata.fda.gov/spl/data/2141c3ca-074a-4098-85da-1ef78ec4d4dc/2141c3ca-074a-4098-85da-1ef78ec4d4dc.xml", "title": "EXENATIDE injection, for subcutaneous use — Prescribing Information (SPL, ANDA 206697)", "publisher": "FDA", "date": "2026-05-27", "quote": "Acute Pancreatitis: Has been observed in patients treated with GLP-1 receptor agonists, including exenatide. Discontinue if pancreatitis is suspected. … Never share an exenatide injection pen between patients, even if the needle is changed." }, "verifiedAt": "2026-08-02" }, { "signal": "In a 104-week rat carcinogenicity study reported in the FDA-approved labeling for immediate-release exenatide injection, benign thyroid C-cell adenomas were observed in female rats at all exenatide dose levels. In a 104-week mouse carcinogenicity study, no evidence of tumors was observed. Exenatide was not mutagenic or clastogenic in the Ames bacterial mutagenicity assay or a chromosomal aberration assay in Chinese hamster ovary cells, and was negative in the in vivo mouse micronucleus assay.", "note": "Recorded because it sits in tension with the boxed-warning asymmetry above and a reader deserves both halves. A rodent thyroid C-cell finding appears in the NONCLINICAL TOXICOLOGY section of the immediate-release label, which carries no boxed warning; the extended-release label carried a boxed warning on a finding described in similar terms. This record does not attempt to explain FDA's line between the two — the exposure multiples, tumour types and formulations differ, and reconstructing a regulatory judgement from two labels would be a guess. The checkable statement is that both findings are in FDA-approved labeling and only one of them was elevated to a boxed warning. Specific dose levels and exposure multiples in the label's text are omitted here under this site's no-dosing policy; no finding above depends on them.", "source": { "url": "https://www.accessdata.fda.gov/spl/data/2141c3ca-074a-4098-85da-1ef78ec4d4dc/2141c3ca-074a-4098-85da-1ef78ec4d4dc.xml", "title": "EXENATIDE injection, for subcutaneous use — Prescribing Information (SPL, ANDA 206697)", "publisher": "FDA", "date": "2026-05-27", "quote": "Benign thyroid C-cell adenomas were observed in female rats at all exenatide doses." }, "verifiedAt": "2026-08-02" }, { "signal": "In FDA's final decision refusing approval of ITCA 650 (exenatide in DUROS device), FDA recorded that more subjects who received ITCA 650 experienced acute kidney injury events than those who received placebo, and that a majority of the serious AKI events in participants randomized to ITCA 650 appeared to be associated with vomiting, diarrhea and dehydration — known adverse reactions associated with exenatide therapy.", "note": "Included because the mechanism generalises even though the product does not. FDA's reasoning links a serious renal outcome to the ordinary gastrointestinal adverse reactions of the class, via volume depletion — which is precisely the pathway the marketed exenatide label warns about under 'Acute Kidney Injury Due to Volume Depletion'. FDA also recorded that sufficient risk mitigation approaches could not be identified, 'particularly because serious AKI events occurred in participants who received ITCA 650 who did not have known risk factors'. SCOPE: this is a finding about ITCA 650, an implanted continuous-delivery product FDA refused to approve. It is not a finding about the approved injection, whose renal risk is handled by a labeled warning rather than a refusal.", "source": { "url": "https://www.federalregister.gov/documents/2024/08/23/2024-18898/final-decision-on-the-proposal-to-refuse-to-approve-a-new-drug-application-for-itca-650", "title": "Final Decision on the Proposal To Refuse To Approve a New Drug Application for ITCA 650 (89 FR 68168)", "publisher": "FDA", "date": "2024-08-23", "quote": "a majority of the serious AKI events in participants randomized to ITCA 650 appeared to be associated with vomiting, diarrhea, and dehydration, which are known adverse reactions associated with exenatide therapy, supporting a causal relationship between ITCA 650 and AKI" }, "verifiedAt": "2026-08-02" } ], "faqs": [ { "question": "Is Byetta still available in 2026?", "answer": "No. FDA withdrew approval of Byetta (NDA 021773) effective 3 September 2025. The Federal Register notice states that the applicants 'have informed FDA that these drug products are no longer marketed and have requested that FDA withdraw approval of the applications under the process in Sec. 314.150(c) (21 CFR 314.150(c))', and that they waived their opportunity for a hearing. The same notice withdrew approval of Bydureon and Bydureon Pen (NDA 022200) and Bydureon BCise (NDA 209210). This is stronger than a discontinuation: FDA states that introducing a product listed in that table into interstate commerce without an approved NDA violates sections 505(a) and 301(d) of the Federal Food, Drug, and Cosmetic Act, though inventory on hand at the effective date could continue to be dispensed until depleted or expired. Exenatide itself is still available as an approved drug — a generic exenatide injection under ANDA 206697 (Amneal Pharmaceuticals) is what remains.", "source": { "url": "https://www.federalregister.gov/documents/2025/08/04/2025-14683/teva-branded-pharmaceutical-products-randd-inc-et-al-withdrawal-of-approval-of-39-new-drug", "title": "Teva Branded Pharmaceutical Products R&D, Inc., et al.; Withdrawal of Approval of 39 New Drug Applications (90 FR 36440)", "publisher": "FDA", "date": "2025-08-04", "quote": "Therefore, approval of the applications listed in table 1, and all amendments and supplements thereto, is hereby withdrawn as of September 3, 2025." }, "verifiedAt": "2026-08-02" }, { "question": "Is exenatide approved for weight loss?", "answer": "No. The FDA-approved labeling for the marketed exenatide product carries exactly one indication: 'Exenatide injection is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.' There is no weight management indication, no cardiovascular risk-reduction indication and no obesity indication. That is true of every exenatide label, not just the current one — the final Byetta label and the last Bydureon BCise label each carry the glycemic indication and nothing else. Exenatide therefore does not follow the rest of the GLP-1 class, several members of which do hold weight-management approvals. Prescribing exenatide for weight loss is off-label use, which is a decision for a licensed prescriber and is not something this label supports.", "source": { "url": "https://www.accessdata.fda.gov/spl/data/2141c3ca-074a-4098-85da-1ef78ec4d4dc/2141c3ca-074a-4098-85da-1ef78ec4d4dc.xml", "title": "EXENATIDE injection, for subcutaneous use — Prescribing Information (SPL, ANDA 206697)", "publisher": "FDA", "date": "2026-05-27", "quote": "Exenatide injection is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus." }, "verifiedAt": "2026-08-02" }, { "question": "Why was Bydureon discontinued?", "answer": "The primary document gives one stated reason and no other: the products were no longer marketed. FDA's Federal Register notice records that the applicants 'informed FDA that these drug products are no longer marketed and have requested that FDA withdraw approval of the applications under the process in Sec. 314.150(c)'. Approval of Bydureon and Bydureon Pen (NDA 022200) and of Bydureon BCise (NDA 209210) was withdrawn effective 3 September 2025. Read that carefully in both directions. The notice records no FDA determination that the products were unsafe or ineffective — but a withdrawal made at the sponsor's request is the absence of a finding, not an endorsement, and the notice does not say the products were withdrawn for reasons other than safety either. FDA also states this kind of withdrawal is 'without prejudice to refiling'. One further oddity worth knowing if you cite a date: both Bydureon applications appear a second time in a later FDA notice withdrawing approval as of 8 April 2026.", "source": { "url": "https://www.federalregister.gov/documents/2025/08/04/2025-14683/teva-branded-pharmaceutical-products-randd-inc-et-al-withdrawal-of-approval-of-39-new-drug", "title": "Teva Branded Pharmaceutical Products R&D, Inc., et al.; Withdrawal of Approval of 39 New Drug Applications (90 FR 36440)", "publisher": "FDA", "date": "2025-08-04", "quote": "The applicants listed in table 1 have informed FDA that these drug products are no longer marketed and have requested that FDA withdraw approval of the applications under the process in Sec. 314.150(c) (21 CFR 314.150(c)). The applicants have also, by their requests, waived their opportunity for a hearing. Withdrawal of approval of an application or abbreviated application under Sec. 314.150(c) is without prejudice to refiling." }, "verifiedAt": "2026-08-02" }, { "question": "Can you still get exenatide if Byetta and Bydureon are gone?", "answer": "Yes — as a generic. Drugs@FDA lists exenatide injection under ANDA 206697 (Amneal Pharmaceuticals), approved 19 November 2024, with marketing status 'Prescription', therapeutic equivalence code AP, and both of its products flagged as reference standard. FDA hosts a current approved label for it with an SPL effective date of 27 May 2026. Note the chronology, because it is unusual: FDA approved the generic nine months before the brand it references lost its approval, and Drugs@FDA now flags the generic as the reference standard — the role the originator used to hold. Only the immediate-release injection survives; there is no marketed extended-release exenatide product, so the once-weekly presentation and the paediatric indication that came with it both left the market with Bydureon.", "source": { "url": "https://api.fda.gov/drug/drugsfda.json?search=products.active_ingredients.name:%22EXENATIDE%22&limit=20", "title": "Drugs@FDA — applications containing exenatide (openFDA drug/drugsfda)", "publisher": "FDA", "date": "2026-07-31" }, "verifiedAt": "2026-08-02" }, { "question": "Does exenatide have a boxed warning for thyroid cancer?", "answer": "It depends entirely on which exenatide product you mean, and the answer flipped when the brands were withdrawn. The extended-release products carried a boxed warning: 'Exenatide extended-release causes an increased incidence in thyroid C-cell tumors at clinically relevant exposures in rats compared to controls. It is unknown whether BYDUREON BCISE causes thyroid C-cell tumors, including medullary thyroid carcinoma (MTC), in humans...' — together with a contraindication in patients with a personal or family history of MTC or with Multiple Endocrine Neoplasia syndrome type 2. Those applications had their approvals withdrawn effective 3 September 2025. The immediate-release exenatide injection that remains on the market carries no boxed warning at all and no MTC or MEN 2 contraindication. Its labeling does still report, in the nonclinical toxicology section, that benign thyroid C-cell adenomas were observed in female rats in a 104-week carcinogenicity study. Same active ingredient, different formulation, different highest-level FDA warning — so a claim about 'exenatide' that does not name the product cannot be checked.", "source": { "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/209210s025lbl.pdf", "title": "BYDUREON BCISE (exenatide) extended-release injectable suspension — Highlights of Prescribing Information (NDA 209210, SUPPL-25)", "publisher": "FDA", "date": "2025-05-28", "quote": "WARNING: RISK OF THYROID C-CELL TUMORS … BYDUREON BCISE is contraindicated in patients with a personal or family history of MTC or in patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2)." }, "verifiedAt": "2026-08-02" }, { "question": "Did FDA ever approve an exenatide implant?", "answer": "No. FDA issued an order refusing to approve NDA 209053 for ITCA 650 (exenatide in DUROS device), an osmotic mini-pump implanted in the subdermal space that was proposed for the same indication as the injection — as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. FDA concluded that 'Intarcia has not demonstrated that ITCA 650 is safe for its intended use' and denied approval. The grounds recorded in FDA's decision include acute kidney injury events occurring more often on ITCA 650 than on placebo, an unresolved cardiovascular risk signal, and drug-delivery variability that FDA found 'compare unfavorably to approved products with a similar or identical active ingredient'. This was a full adjudicated refusal after a hearing request, not a complete response letter — the notice is dated 23 August 2024, following an NDA first submitted in November 2016.", "source": { "url": "https://www.federalregister.gov/documents/2024/08/23/2024-18898/final-decision-on-the-proposal-to-refuse-to-approve-a-new-drug-application-for-itca-650", "title": "Final Decision on the Proposal To Refuse To Approve a New Drug Application for ITCA 650 (89 FR 68168)", "publisher": "FDA", "date": "2024-08-23", "quote": "FDA has determined that the approval criteria in the FD&C Act have not been met because Intarcia has failed to demonstrate that ITCA 650 is safe for its intended conditions of use." }, "verifiedAt": "2026-08-02" } ] }, { "slug": "ghk-cu", "name": "GHK-Cu", "aliases": [ "Copper tripeptide-1", "Glycyl-L-histidyl-L-lysine copper(II)", "GHK-Cu(II)", "Tripeptide-copper complex", "TCC", "Iamin" ], "url": "https://peptides101.com/compounds/ghk-cu", "moleculeNote": "The tripeptide glycyl-L-histidyl-L-lysine (GHK) complexed with copper(II). GHK and GHK-Cu are distinct substances, and FDA's Category 1 entry names only GHK-Cu. The older wound-healing literature calls the same complex 'tripeptide-copper complex' (TCC) or by the Procyte trade name Iamin, so a search for 'GHK-Cu' alone misses the two human RCTs that actually exist.", "quickAnswer": "GHK-Cu is not approved by FDA for any use: FDA lists GHK-Cu in Category 1 of its 503A nomination process — under evaluation, which is not approval and not a finding of safety — and only for non-injectable routes, with FDA intending to consult its Pharmacy Compounding Advisory Committee about GHK-Cu before the end of February 2027. FDA has separately stated that injectable GHK-Cu may pose an immunogenicity risk and that there are limited data in humans to inform safety, and the only two randomised trials of GHK-Cu that have reported results were both topical and both reported no significant benefit on their objective endpoints.", "fdaStatus": { "value": "not-approved", "note": "Not an FDA-approved drug for any indication, and not in active development toward approval. That says nothing about whether it is sold — it is.", "source": { "url": "https://www.fda.gov/media/94155/download", "title": "Bulk Drug Substances Nominated for Use in Compounding Under Section 503A of the Federal Food, Drug, and Cosmetic Act", "publisher": "FDA", "date": "2026-05-14", "quote": "GHK-Cu (except for injectable routes of administration) was removed from category 1 on April 22, 2026, because the nominations for GHK-Cu were withdrawn by the nominators. On May 5, 2026, one of those nominators clarified that it intended to withdraw only its nomination of the injectable route of administration with respect to GHK-Cu and would like to retain its nomination for GHK-Cu for non-injectable routes of administration." }, "verifiedAt": "2026-07-16" }, "compoundingStatus": { "value": "category-1", "note": "SCOPE IS EVERYTHING, AND THE SCOPE EXCLUDES INJECTION. Verified by fetching and text-extracting the list updated 2026-05-14: GHK-Cu appears exactly once in the categories, in Category 1, written as 'GHK-Cu (except for injectable routes of administration)'. It is not in Category 2 (which contains exactly six substances, and GHK-Cu is not among them) and not in Category 3. But do not read that as GHK-Cu never having carried a safety concern: FDA's safety-risks page lists 'GHK-Cu (for injectable routes of administration)' among substances PREVIOUSLY in category 2 and withdrawn by the nominators — see fdaFindings. Absence from the current Category 2 table reflects the withdrawal of the injectable nomination, not a resolution of the concern. The sequence was: nominations withdrawn 2026-04-22, removing it from Category 1 entirely; one nominator clarified on 2026-05-05 that it meant to withdraw only the INJECTABLE route; the non-injectable scope will be added back to Category 1. FDA has announced it intends to consult the Pharmacy Compounding Advisory Committee before the end of February 2027 regarding potential inclusion on the 503A bulks list — so GHK-Cu is NOT among the seven substances before PCAC on 2026-07-23/24. Two things this status is not. It is not the 503A bulks list — Category 1 means under evaluation, and evaluation is not approval, endorsement, or a safety finding. And it is not a licence for the injectable route, which is the one route the nominator affirmatively dropped.", "source": { "url": "https://www.fda.gov/media/94155/download", "title": "Bulk Drug Substances Nominated for Use in Compounding Under Section 503A of the Federal Food, Drug, and Cosmetic Act", "publisher": "FDA", "date": "2026-05-14", "quote": "GHK-Cu (except for injectable routes of administration) was removed from category 1 on April 22, 2026, because the nominations for GHK-Cu were withdrawn by the nominators. On May 5, 2026, one of those nominators clarified that it intended to withdraw only its nomination of the injectable route of administration with respect to GHK-Cu and would like to retain its nomination for GHK-Cu for non-injectable routes of administration." }, "verifiedAt": "2026-07-16" }, "evidence": { "tier": "promising-but-unproven", "humanAdministrationChecked": true, "note": "THE TRIAL COUNT IS REAL AND IT POINTS THE WRONG WAY. Both cited studies were opened and confirmed to ADMINISTER GHK-Cu to humans — neither is an endogenous-biomarker study — and both are null on their objective endpoints. Bishop 1992 (J Vasc Surg, n=86 evaluable, venous stasis ulcers, randomised, evaluator-blinded, vehicle-placebo-controlled): tripeptide-copper complex 0.4% cream was NO DIFFERENT FROM PLACEBO, and silver sulfadiazine beat both. This is a controlled human trial in which GHK-Cu failed. Miller 2006 (Arch Facial Plast Surg, n=13 completers, CO2 laser-resurfaced circumoral skin, randomised): researchers reported no statistically significant difference between groups for resolution of erythema, and no significant improvement in wrinkles or overall skin quality on objective evaluation; only a patient-completed questionnaire reached significance (P = .04). Limitations: thirteen completers, and the single positive endpoint is self-reported satisfaction in a trial whose blinded and computer-analysed endpoints were negative. Tier reasoning: not animal-or-in-vitro-only, because genuine human administration RCTs exist; not no-credible-evidence, because controlled ANIMAL wound-healing data reporting benefit does exist (rabbit and rat models); not proven-in-humans, because the human trials did not establish efficacy. 'Promising-but-unproven' is the enum's bucket for programmes that were tested and failed, which is what this is — the label is more generous than the data. ROUTE ASYMMETRY: both human RCTs are TOPICAL. We found no human administration data for injectable GHK-Cu by any route, at any phase — which is precisely the route being sold and precisely the route whose nomination was withdrawn. NOT COUNTED, DELIBERATELY: NCT07437586 ('Topical GHK-Cu Gel for Acute Skin Wound Healing') is a Hudson Biotech registration — a sponsor that sells research peptides — start date 2026-02-02, still RECRUITING, hasResults false. It matches the contamination pattern of eight registrations from one sponsor and one site, all starting February 2026. A registration is a self-reported filing, not evidence, and this one has produced no data. Also not counted: Watson 2009 (Br J Dermatol), which vendor pages and AI summaries routinely cite as GHK-Cu's strongest human evidence. We read it. It tests an unnamed over-the-counter 'cosmetic anti-ageing product' and never identifies GHK-Cu as an ingredient anywhere in the record, so it cannot support a GHK-Cu claim — and its own 6-month between-group comparison for facial wrinkles was non-significant regardless.", "source": { "url": "https://pubmed.ncbi.nlm.nih.gov/1495150/", "title": "A prospective randomized evaluator-blinded trial of two potential wound healing agents for the treatment of venous stasis ulcers", "publisher": "PubMed", "date": "1992-08-01", "quote": "Silver sulfadiazine 1% in a cream proved to statistically reduce the ulcer size compared with a biologically active tripeptide copper complex 0.4% cream formulation or the placebo. There was no difference between the latter two treatments." }, "verifiedAt": "2026-07-16" }, "fdaApproval": null, "fdaFindings": [ { "finding": "FDA has not made any determination on GHK-Cu. It is in Category 1 — under evaluation — for non-injectable routes only, and FDA intends to consult the Pharmacy Compounding Advisory Committee before the end of February 2027 regarding its potential inclusion on the 503A bulks list.", "note": "Unlike the seven substances before PCAC on 2026-07-23/24, GHK-Cu has no FDA briefing document, so there is no full FDA efficacy review of GHK-Cu to quote and no 'we propose not adding' finding, because FDA has not yet written one. The absence of that finding is not a positive FDA finding — it is a pending evaluation with a stated deadline. CORRECTED 2026-07-16: an earlier version of this note said GHK-Cu had 'no published FDA safety or efficacy review to quote' at all. That was wrong, and wrong in the direction that flatters the compound. FDA has published a safety characterisation of the INJECTABLE route on its safety-risks page — immunogenicity risk, limited human data — quoted in full below. What GHK-Cu lacks is a PCAC briefing document, which is a narrower claim than the one this note used to make.", "source": { "url": "https://www.fda.gov/media/94155/download", "title": "Bulk Drug Substances Nominated for Use in Compounding Under Section 503A of the Federal Food, Drug, and Cosmetic Act", "publisher": "FDA", "date": "2026-05-14", "quote": "FDA has announced it intends to consult the Pharmacy Compounding Advisory Committee (PCAC) before the end of February 2027 regarding the potential inclusion of GHK-Cu on the 503A bulks list." }, "verifiedAt": "2026-07-16" }, { "finding": "The injectable route of administration is excluded from the surviving nomination, so the route most commonly sold to consumers is not the route FDA is evaluating.", "note": "The Category 1 entry is written verbatim as 'GHK-Cu (except for injectable routes of administration)'. Read plainly: a nominator withdrew the injectable nomination and kept the non-injectable one. Any future addition to the bulks list under this nomination would carry the same carve-out. Coverage framing this as 'GHK-Cu is back in Category 1' drops the parenthetical, which is the only part that determines what a compounder could ever lawfully make.", "source": { "url": "https://www.fda.gov/media/94155/download", "title": "Bulk Drug Substances Nominated for Use in Compounding Under Section 503A of the Federal Food, Drug, and Cosmetic Act", "publisher": "FDA", "date": "2026-05-14" }, "verifiedAt": "2026-07-16" }, { "finding": "FDA has published a safety characterisation of INJECTABLE GHK-Cu specifically: it lists 'GHK-Cu (for injectable routes of administration)' among bulk drug substances it describes as previously in category 2 — its category for substances that may present significant safety risks — and withdrawn by the nominators. FDA's stated concern is immunogenicity, and FDA characterises the human data as limited.", "note": "THIS IS THE FDA FINDING THE RECORD PREVIOUSLY LACKED, AND IT INVERTS THE OBVIOUS READING OF THE CARVE-OUT. The 503A bulks list alone makes the injectable exclusion look like a clerical act — a nominator narrowing its own paperwork. This page shows FDA had already written a significant-safety-risk characterisation for the injectable route. The two documents are consistent and they are not the same fact: one records that the injectable nomination is gone, the other records what FDA said about it while it was there. Scope discipline, because the sentence is quotable and therefore easy to over-read. 'There are limited data in humans to inform safety-related considerations' is FDA reporting an ABSENCE OF INFORMATION, not a finding of harm. It is not evidence that injectable GHK-Cu hurt anyone; no such evidence is cited here or anywhere we found. It is also not evidence that it is safe — an agency saying it lacks the data to know is the opposite of an agency saying there is nothing to find. Two limits we hold deliberately. The table mixes the 503A and 503B interim policies and has no date column, so we do not say under which policy or from when injectable GHK-Cu was in category 2. And note the polarity of the parentheticals across the two documents: Category 1 covers GHK-Cu '(except for injectable routes of administration)'; this page covers GHK-Cu '(for injectable routes of administration)'. The route that FDA flagged is exactly the route the surviving nomination excludes, and exactly the route the market sells.", "source": { "url": "https://www.fda.gov/drugs/human-drug-compounding/certain-bulk-drug-substances-use-compounding-may-present-significant-safety-risks", "title": "Certain Bulk Drug Substances for Use in Compounding May Present Significant Safety Risks", "publisher": "FDA", "date": "2026-04-22", "quote": "Compounded injectable drugs containing GHK-Cu may pose risk for immunogenicity due to the potential for aggregation and peptide-related impurities. There are limited data in humans to inform safety-related considerations." }, "verifiedAt": "2026-07-16" } ], "safetySignals": [ { "signal": "One serious FAERS report (safetyreportid 25484639, received 2025-06-26) names GHK-Cu as a CONCOMITANT — not a suspect — product in an anaphylactic shock event whose sole suspect drug was sermorelin acetate. The reported reactions include anaphylactic shock, syncope, loss of consciousness, decreased blood pressure and decreased heart rate.", "note": "THE CODING IS THE FINDING — DO NOT ATTRIBUTE THIS EVENT TO GHK-Cu. In this report GHK-Cu carries drugcharacterization=2, which openFDA's own field reference defines as 'Concomitant (the drug was reported as being taken along with the suspect drug)'. BPC-157 is likewise coded 2. Only SERMORELIN ACETATE is coded drugcharacterization=1 (Suspect), and it is the only drug in the report carrying a route (058) and an indication (growth hormone deficiency); no route or indication is recorded for GHK-Cu at all. So the reporter did not identify GHK-Cu as a cause — the report affirmatively records it as a drug taken alongside the one that was suspected. It is also a consumer report (primary source qualification 3), unverified by a health professional, and it is exactly one report — the entire FAERS return for this query is one record. We record it because it is the only documented human safety report naming GHK-Cu that we could find, and because omitting it would be as dishonest as overstating it. It establishes that a person who used GHK-Cu had a serious event attributed by the reporter to a different drug. It establishes nothing about GHK-Cu's causation, and it is not a GHK-Cu safety finding.", "source": { "url": "https://api.fda.gov/drug/event.json?search=patient.drug.medicinalproduct:%22GHK-CU%22", "title": "FDA Adverse Event Reporting System (FAERS) — public dashboard API, GHK-Cu query", "publisher": "FDA", "date": "2025-06-26", "quote": "{\"drugcharacterization\": \"2\", \"medicinalproduct\": \"GHK-Cu\"}" }, "verifiedAt": "2026-07-16" }, { "signal": "A 2026 narrative review in the American Journal of Sports Medicine reported that no clinical data support the use of GHK-Cu for musculoskeletal conditions.", "note": "A narrative review, not primary data — cited for its scope statement, not as evidence of effect. Relevant here because it is the injectable-orthopaedic market that the reviewers surveyed, and it is the injectable route that the 503A nomination excludes. The same review notes that indications, dosing, frequency and duration remain unknown for these peptides generally.", "source": { "url": "https://pubmed.ncbi.nlm.nih.gov/41476424/", "title": "Injectable Peptide Therapy: A Primer for Orthopaedic and Sports Medicine Physicians", "publisher": "PubMed", "date": "2026-01-01", "quote": "GHK-Cu showed promise in wound healing and anti-inflammatory effects, but no clinical data support its use for musculoskeletal conditions." }, "verifiedAt": "2026-07-16" } ], "faqs": [ { "question": "Did GHK-Cu become legal again when FDA put it back in Category 1?", "answer": "No. Category 1 on FDA's 503A list means a substance is under evaluation for possible future inclusion on the compounding bulks list — it is not FDA approval, not a finding that GHK-Cu is safe, and not permission to sell, buy, or use it. GHK-Cu was removed from Category 1 on April 22, 2026 because its nominators withdrew the nominations, and it returns only in the narrowed form FDA writes verbatim as 'GHK-Cu (except for injectable routes of administration)' after one nominator clarified on May 5, 2026 that it had meant to withdraw only the injectable route. Nothing in that sequence was granted to anyone: the status moved sideways, not toward legality.", "source": { "url": "https://www.fda.gov/media/94155/download", "title": "Bulk Drug Substances Nominated for Use in Compounding Under Section 503A of the Federal Food, Drug, and Cosmetic Act", "publisher": "FDA", "date": "2026-05-14", "quote": "GHK-Cu (except for injectable routes of administration) was removed from category 1 on April 22, 2026, because the nominations for GHK-Cu were withdrawn by the nominators." }, "verifiedAt": "2026-07-16" }, { "question": "Is injectable GHK-Cu legal to buy or compound in 2026?", "answer": "No route of GHK-Cu is FDA-approved, and the injectable route is the one route excluded from the only GHK-Cu nomination FDA is still evaluating — its Category 1 entry reads 'GHK-Cu (except for injectable routes of administration)'. FDA's safety-risks page separately lists 'GHK-Cu (for injectable routes of administration)' among substances it describes as previously in category 2 — FDA's category for substances that may present significant safety risks — and withdrawn by the nominators, stating that compounded injectable GHK-Cu may pose a risk for immunogenicity and that there are limited data in humans to inform safety. Injectable GHK-Cu is nonetheless the form most widely sold.", "source": { "url": "https://www.fda.gov/drugs/human-drug-compounding/certain-bulk-drug-substances-use-compounding-may-present-significant-safety-risks", "title": "Certain Bulk Drug Substances for Use in Compounding May Present Significant Safety Risks", "publisher": "FDA", "date": "2026-04-22", "quote": "Compounded injectable drugs containing GHK-Cu may pose risk for immunogenicity due to the potential for aggregation and peptide-related impurities. There are limited data in humans to inform safety-related considerations." }, "verifiedAt": "2026-07-16" }, { "question": "Is there any human evidence that GHK-Cu works?", "answer": "Two randomised controlled trials have administered GHK-Cu to humans and reported their results, and both reported no significant benefit on their objective endpoints. In a 1992 evaluator-blinded trial of 86 evaluable patients with venous stasis ulcers, researchers reported that a tripeptide copper complex cream was no different from placebo, and that silver sulfadiazine cream outperformed both. In a 2006 randomised trial of 13 completers with CO2 laser-resurfaced skin, researchers reported that computer analysis and blinded evaluators found no statistically significant difference between groups. Both trials were topical; no human trial data for injectable GHK-Cu was found by any route.", "source": { "url": "https://pubmed.ncbi.nlm.nih.gov/1495150/", "title": "A prospective randomized evaluator-blinded trial of two potential wound healing agents for the treatment of venous stasis ulcers", "publisher": "PubMed", "date": "1992-08-01", "quote": "Eighty-six evaluable patients completed the trial. Silver sulfadiazine 1% in a cream proved to statistically reduce the ulcer size compared with a biologically active tripeptide copper complex 0.4% cream formulation or the placebo. There was no difference between the latter two treatments." }, "verifiedAt": "2026-07-16" }, { "question": "Does GHK-Cu help skin healing or wrinkles after laser resurfacing?", "answer": "Not on any objective measure, in the one randomised trial that tested it. Researchers reporting on 13 patients who completed a 2006 randomised trial of circumoral CO2 laser-resurfaced skin found no statistically significant difference between the copper tripeptide complex group and the control group for earlier resolution of erythema, on both computer analysis and blinded evaluator assessment. Every patient in the trial improved significantly in wrinkles and overall skin quality, but the researchers reported no difference between the groups — so the improvement tracked the laser resurfacing, not the group assignment. One endpoint did separate: on a patient-completed questionnaire, researchers reported a significant difference in improvement of overall skin quality favouring the GHK-Cu group (P = .04). That endpoint is self-reported, in a trial whose blinded and computer-analysed endpoints were negative. GHK-Cu is not FDA-approved for wound healing, skin healing, or any other indication.", "source": { "url": "https://pubmed.ncbi.nlm.nih.gov/16847171/", "title": "Effects of topical copper tripeptide complex on CO2 laser-resurfaced skin", "publisher": "PubMed", "date": "2006-07-01", "quote": "Thirteen patients completed the study. Computer analysis and blinded evaluators found no statistically significant differences between groups for earlier resolution of erythema. All the patients experienced significant improvement in wrinkles and overall skin quality, but no differences were found between groups. The results of the questionnaire indicated a significant difference in the posttreatment improvement of overall skin quality for patients using GHK-Cu (P = .04)." }, "verifiedAt": "2026-07-16" }, { "question": "Who withdrew the GHK-Cu nomination, and why does it matter?", "answer": "Private nominators withdrew it, not FDA. In an April 14, 2026 filing to FDA docket FDA-2015-N-3534, Wells Pharmacy Network withdrew its nominations of twelve peptide bulk drug substances, listing GHK-Cu fifth. This matters because it establishes the direction of the change: the parties seeking to have GHK-Cu evaluated for compounding gave up on that request. FDA granted nothing, approved nothing, and made no finding about GHK-Cu in the process.", "source": { "url": "https://www.regulations.gov/document/FDA-2015-N-3534-0484", "title": "Withdrawal from Wells Pharmacy Network — Docket FDA-2015-N-3534", "publisher": "Regulations.gov (FDA)", "date": "2026-04-14", "quote": "Wells Pharmacy Network hereby withdraws the following nominations of Bulk Drug Substances That Can Be Used To Compound Drug Products in Accordance With Section 503A of the Federal Food, Drug, and Cosmetic Act: 1. Emideltide (DSIP) 2. BPC-157 3. Semax 4. Epitalon (Epithalon) 5. GHK-Cu 6. Melanotan II ..." }, "verifiedAt": "2026-07-16" }, { "question": "Was GHK-Cu withdrawn by more than one nominator?", "answer": "Yes — two separate filers withdrew GHK-Cu on the same day, April 14, 2026, in FDA docket FDA-2015-N-3534. Wells Pharmacy Network withdrew twelve peptide bulk drug substances, and LDT Health Solutions, Inc. separately withdrew six, GHK-Cu among them. That both filings landed together is why FDA's 503A bulks list refers to 'the nominators' in the plural, and why it records that only one of them later clarified it had meant to withdraw just the injectable route — the clarification that produced the surviving Category 1 entry for non-injectable routes. Neither filing is an FDA action, and neither says anything about whether GHK-Cu works or is safe.", "source": { "url": "https://www.regulations.gov/document/FDA-2015-N-3534-0485", "title": "Withdrawal from LDT Health Solutions, Inc. — Docket FDA-2015-N-3534", "publisher": "Regulations.gov (FDA)", "date": "2026-04-14", "quote": "LDT Health Solutions, Inc. hereby withdraws the nomination of Emideltide (DSIP), BPC-157, Semax, Epitalon, GHK-Cu, and Melanotan II to Bulk Drug Substances That Can Be Used To Compound Drug Products in Accordance With Section 503A of the Federal Food, Drug, and Cosmetic Act ..." }, "verifiedAt": "2026-07-16" } ] }, { "slug": "glucagon", "name": "Glucagon", "aliases": [ "Baqsimi", "Gvoke", "Gvoke HypoPen", "Gvoke PFS", "Gvoke Kit", "Gvoke VialDx", "GlucaGen", "glucagon hydrochloride", "glucagon (rDNA origin)", "G-Pen", "LY900018" ], "url": "https://peptides101.com/compounds/glucagon", "moleculeNote": "A peptide hormone, and one of the few substances on this site that is simultaneously endogenous and an approved drug. FDA-approved labeling for GVOKE describes it verbatim as 'a single chain containing 29 amino acid residues', with 'a molecular weight of 3483', 'identical to human glucagon' and 'of synthetic origin produced by solid phase synthesis'. Two disambiguations matter when reading a carton. FIRST, ACTIVE MOIETY: Drugs@FDA records some glucagon products with the active ingredient 'GLUCAGON' (Gvoke, Baqsimi, the modern generic vials) and others with 'GLUCAGON HYDROCHLORIDE' expressed as equivalent base (Fresenius Kabi's NDA 201849, Novo Nordisk's GlucaGen, Lilly's original NDA 012122). SECOND, and more consequential, PRESENTATION: 'Glucagon for Injection' is not one product. Under a single application number, NDA 201849, Fresenius Kabi markets one presentation approved for both severe hypoglycemia and diagnostic use and another approved only as a diagnostic aid, whose own labeling states it is not indicated for the emergency treatment of hypoglycemia. The generic name on the vial does not identify which one you are holding.", "quickAnswer": "Glucagon is an FDA-approved drug as well as a human hormone, marketed in the United States under NDA 212097 (Gvoke and Gvoke VialDx, Xeris), NDA 210134 (Baqsimi nasal powder, Amphastar) and NDA 201849 (Glucagon for Injection, Fresenius Kabi), with the first glucagon application approved on 14 November 1960. Across those labels FDA has approved glucagon for exactly two things: treating severe hypoglycemia in patients with diabetes, and use as a diagnostic aid during radiologic examinations to temporarily inhibit movement of the gastrointestinal tract. No label read for this record approves glucagon for weight loss, body composition or metabolic enhancement. The products are not interchangeable — one presentation of Glucagon for Injection under NDA 201849 states in its own FDA-approved labeling that it 'is not indicated for the emergency treatment of hypoglycemia', and the approved paediatric age floor is two years for Gvoke and one year for Baqsimi. FDA-approved labeling also records limits on when glucagon works and when it must not be given: Baqsimi labeling states it 'is effective in treating hypoglycemia only if sufficient hepatic glycogen is present', and the products are contraindicated in pheochromocytoma and in insulinoma. Glucagon appears in none of Categories 1, 2 or 3 of FDA's 503A bulk drug substances list updated 14 May 2026 — an absence that reflects its status as a component of approved drugs rather than a withdrawn or rejected nomination.", "fdaStatus": { "value": "approved", "note": "FDA-approved, and approved for a long time — Drugs@FDA records the original Lilly glucagon application, NDA 012122, as approved on 1960-11-14. Approval is always for a specific indication and population, and glucagon's are unusually narrow relative to the breadth of the word: see the approval record below and the verbatim indications recorded under fdaFindings. COMPOUNDING STATUS IS DELIBERATELY OMITTED FROM THIS RECORD. Glucagon appears nowhere in FDA's 503A bulk drug substances list updated 2026-05-14 — verified by fetching and text-extracting the document on 2026-08-02, zero hits for 'glucagon' across all seven pages. That absence is recorded as a finding below rather than as a status, because asserting a 503A category would imply glucagon was part of a nomination proceeding it was never in. A 503A bulks nomination is a route for substances WITHOUT an approved product; glucagon has several.", "source": { "url": "https://www.accessdata.fda.gov/spl/data/8c693dd2-e196-41fe-bd0f-584c1254174c/8c693dd2-e196-41fe-bd0f-584c1254174c.xml", "title": "GVOKE (glucagon) injection and GVOKE VialDx (glucagon) injection — Highlights of Prescribing Information (SPL)", "publisher": "FDA", "date": "2025-12-23", "quote": "GVOKE is an antihypoglycemic agent indicated for subcutaneous use for the treatment of severe hypoglycemia in adult and pediatric patients aged two years and older with diabetes (1.1) GVOKE VialDx is a gastrointestinal motility inhibitor indicated for intravenous use as a diagnostic aid during radiologic examinations to temporarily inhibit movement of the gastrointestinal tract in adult patients (1.2)" }, "verifiedAt": "2026-08-02" }, "compoundingStatus": null, "evidence": { "tier": "proven-in-humans", "humanAdministrationChecked": true, "note": "ADMINISTRATION CHECK RUN, NOT ASSUMED — and on this compound the check is not a formality, because glucagon is the single worst offender for the endogenous-biomarker trap that reduces MOTS-c and TB-500 from an apparent five human trials to an actual zero. Glucagon is a hormone every human already secretes, and the literature contains a very large number of studies that MEASURE circulating glucagon as a metabolic readout without administering anything. None of those count. The four trials named here were opened individually on ClinicalTrials.gov on 2026-08-02 and every one records intervention type DRUG with glucagon given to participants. BAQSIMI (NDA 210134), section 14.1 of the label: Study 1 is NCT03339453 — Eli Lilly and Company, phase 1, randomised open-label 2-period crossover in adults with type 1 diabetes, enrolment 70 ACTUAL, status COMPLETED (primary completion 2017-12-17 ACTUAL), results posted; interventions 'Nasal Glucagon' (Administered nasally) and 'Intramuscular Glucagon' (Administered IM). Study 2 is NCT01994746 — same sponsor, phase 3, randomised open-label 2-period crossover, enrolment 77 ACTUAL, COMPLETED 2015-01, results posted. GVOKE (NDA 212097), section 14.1: Study A is NCT02656069 — Xeris Pharmaceuticals, phase 3, randomised crossover, TRIPLE masking, enrolment 80 ACTUAL, COMPLETED (primary completion 2017-08-14 ACTUAL), results posted. Study B is NCT03439072 — same sponsor, phase 3, randomised crossover, SINGLE masking, enrolment 81 ACTUAL, COMPLETED 2018-04-18, results posted. Both compared a glucagon injection against another glucagon injection. TWO DISCREPANCIES, recorded rather than smoothed over. (1) The BAQSIMI label states Study 2 'enrolled 83 patients' while the registry records enrolment 77 ACTUAL; the label's own efficacy analysis population is 80. We have not reconciled these and do not assert a single number. (2) The label describes GVOKE Study A as 'double-blinded' while the registry records TRIPLE masking. Neither discrepancy touches whether the drug was administered, which is what this tier turns on. SCOPE — the tier attaches to the approved indications and the approved products, and travels no further. Every trial above tested reversal of insulin-induced hypoglycaemia against an active glucagon comparator on a non-inferiority design. None of them is evidence about any other use of glucagon, and a non-inferiority result against another glucagon product is not a placebo-controlled demonstration of anything else.", "source": { "url": "https://clinicaltrials.gov/study/NCT03339453", "title": "Comparison of Glucagon Administered by Either the Nasal (LY900018) or Intra-muscular (GlucaGen) Routes in Adult Patients With Type 1 Diabetes Mellitus During Controlled Insulin-Induced Hypoglycemia", "publisher": "ClinicalTrials.gov", "date": "2017-12-17", "quote": "Nasal Glucagon | Administered nasally" }, "verifiedAt": "2026-08-02" }, "fdaApproval": { "applicationNumber": "NDA 212097 (Gvoke HypoPen, Gvoke PFS, Gvoke Kit, Gvoke VialDx — Xeris); NDA 210134 (Baqsimi nasal powder — Amphastar); NDA 201849 (Glucagon for Injection — Fresenius Kabi); NDA 020928 and NDA 012122 (Glucagon — Lilly, both recorded Discontinued); NDA 020918 (GlucaGen — Novo Nordisk, recorded Discontinued); plus ANDA 204468 (Mylan), ANDA 208086 (Amphastar), ANDA 214457 (Lupin), ANDA 218813 (Cipla)", "brandName": "Gvoke, Gvoke VialDx, Baqsimi, GlucaGen, Glucagon", "approvedIndication": "1.1 Severe Hypoglycemia in Adult and Pediatric Patients Aged 2 Years and Older with Diabetes — GVOKE is indicated for subcutaneous use for the treatment of severe hypoglycemia in adult and pediatric patients aged two and older with diabetes. 1.2 Diagnostic Aid in Adults — GVOKE VialDx is indicated for intravenous use as a diagnostic aid during radiologic examinations to temporarily inhibit movement of the gastrointestinal tract in adult patients.", "discontinued": false, "source": { "url": "https://www.accessdata.fda.gov/spl/data/8c693dd2-e196-41fe-bd0f-584c1254174c/8c693dd2-e196-41fe-bd0f-584c1254174c.xml", "title": "GVOKE (glucagon) injection and GVOKE VialDx (glucagon) injection — Highlights of Prescribing Information (SPL)", "publisher": "FDA", "date": "2025-12-23" }, "verifiedAt": "2026-08-02" }, "fdaFindings": [ { "finding": "Drugs@FDA records twelve applications with glucagon or glucagon hydrochloride as an active ingredient: NDA 012122 and NDA 020928 (Lilly), NDA 020918 (Novo Nordisk, GlucaGen), NDA 201849 (Fresenius Kabi), NDA 210134 (Amphastar, Baqsimi), NDA 212097 (Xeris, Gvoke), ANDA 071022 and ANDA 071023 (Quad), ANDA 204468 (Mylan), ANDA 208086 (Amphastar), ANDA 214457 (Lupin) and ANDA 218813 (Cipla). The earliest, NDA 012122, was approved on 1960-11-14.", "note": "RECORDED PRIMARILY AS A QUERY WARNING, because this record nearly published a wrong count. Searching the same endpoint on `openfda.generic_name:\"glucagon\"` returns SEVEN applications, not twelve: the openfda block is empty on NDA 012122, NDA 020918, NDA 020928, ANDA 071022 and ANDA 071023, so a generic_name query drops the original 1960 approval and GlucaGen entirely. The site has already published one false 'not in Drugs@FDA' claim generated exactly this way. Query by `products.active_ingredients.name` and cross-check. Marketing status as recorded on 2026-07-31: Prescription for Gvoke HypoPen (both presentations), Gvoke PFS (one presentation), Gvoke Kit, Baqsimi, both Fresenius Kabi presentations and all four modern ANDAs; Discontinued for Gvoke VialDx, one Gvoke PFS presentation, both GlucaGen presentations, both Lilly NDAs and both Quad ANDAs.", "source": { "url": "https://api.fda.gov/drug/drugsfda.json?search=products.active_ingredients.name:%22GLUCAGON%22&limit=100", "title": "Drugs@FDA — applications with glucagon or glucagon hydrochloride as an active ingredient", "publisher": "FDA", "date": "2026-07-31" }, "verifiedAt": "2026-08-02" }, { "finding": "One presentation of Glucagon for Injection under NDA 201849 is approved ONLY as a diagnostic aid, and its FDA-approved labeling carries a Limitation of Use stating that it is not indicated for the emergency treatment of hypoglycemia because it is not packaged with a syringe and diluent necessary for rapid preparation and administration during an emergency outside of a healthcare facility.", "note": "The single most useful sentence on this record, and it is easy to miss because nothing about the product name signals it. Same application number as the dual-indication presentation, same sponsor, same words on the carton — 'Glucagon for Injection'. FDA's stated reason is not pharmacological, it is about PACKAGING: the presentation is not supplied with what a caregiver would need to reconstitute and inject it under emergency conditions. That is a distinction no amount of reading about the molecule would surface, and it is the kind of distinction that disappears entirely once a substance is discussed by its generic name alone.", "source": { "url": "https://www.accessdata.fda.gov/spl/data/9e17207f-b348-4be8-8416-2f0aa1392390/9e17207f-b348-4be8-8416-2f0aa1392390.xml", "title": "Glucagon for Injection (diagnostic aid presentation, NDA 201849) — Highlights of Prescribing Information (SPL)", "publisher": "FDA", "date": "2022-04-01", "quote": "Glucagon for Injection is indicated for use as a diagnostic aid during radiologic examinations to temporarily inhibit movement of the gastrointestinal tract. Limitations of Use: Glucagon for Injection is not indicated for the emergency treatment of hypoglycemia because it is not packaged with a syringe and diluent necessary for rapid preparation and administration during an emergency outside of a healthcare facility." }, "verifiedAt": "2026-08-02" }, { "finding": "BAQSIMI (NDA 210134) is indicated for the treatment of severe hypoglycemia in adults and pediatric patients aged 1 year and older with diabetes. It carries no diagnostic indication.", "note": "Recorded verbatim because the age floor differs from GVOKE's and because BAQSIMI is the one non-injected glucagon product — a nasal powder, absorbed across the nasal mucosa. Note also a sponsor change the secondary corpus has largely not caught up with: Drugs@FDA records the sponsor of NDA 210134 as Amphastar Pharmaceuticals, and the current label directs adverse-event reporting to Amphastar, not to Eli Lilly, which developed the product and sponsored its pivotal trials.", "source": { "url": "https://www.accessdata.fda.gov/spl/data/54988ebe-c60f-a434-e063-6394a90a20d5/54988ebe-c60f-a434-e063-6394a90a20d5.xml", "title": "BAQSIMI (glucagon) nasal powder — Highlights of Prescribing Information (SPL)", "publisher": "FDA", "date": "2026-06-19", "quote": "BAQSIMI is an antihypoglycemic agent indicated for the treatment of severe hypoglycemia in adults and pediatric patients aged 1 year and older with diabetes." }, "verifiedAt": "2026-08-02" }, { "finding": "The dual-indication presentation of Glucagon for Injection under NDA 201849 is indicated for the treatment of severe hypoglycemia in pediatric and adult patients with diabetes, and as a diagnostic aid for use during radiologic examinations to temporarily inhibit movement of the gastrointestinal tract in adult patients.", "note": "The counterpart to the Limitation-of-Use label above, recorded so that the contrast is carried by two sourced labels rather than by one label and an assertion. Both are NDA 201849. Both are Fresenius Kabi. Both are 'Glucagon for Injection'. Only this one is approved for the emergency use most people assume the name implies. Note this label states no numeric paediatric age floor, where GVOKE's is two years and BAQSIMI's is one.", "source": { "url": "https://www.accessdata.fda.gov/spl/data/3d6add4a-5d95-4e63-9761-7e97a92137ba/3d6add4a-5d95-4e63-9761-7e97a92137ba.xml", "title": "Glucagon for Injection (severe hypoglycemia and diagnostic aid presentation, NDA 201849) — Highlights of Prescribing Information (SPL)", "publisher": "FDA", "date": "2025-03-31", "quote": "Glucagon for Injection is an antihypoglycemic agent and a gastrointestinal motility inhibitor indicated: for the treatment of severe hypoglycemia in pediatric and adult patients with diabetes (1.1) as a diagnostic aid for use during radiologic examinations to temporarily inhibit movement of the gastrointestinal tract in adult patients (1.2)" }, "verifiedAt": "2026-08-02" }, { "finding": "Glucagon appears in none of Categories 1, 2 or 3 of FDA's 503A bulk drug substances list updated 2026-05-14.", "note": "Recorded to close a misreading, not to assert a status — which is why this record carries no compoundingStatus field at all. Verified by fetching the document with a browser user-agent and text-extracting it locally on 2026-08-02: zero hits for 'glucagon' across all seven pages. This absence means something entirely different from BPC-157's absence. BPC-157 was nominated and left Category 2 when its nominators withdrew. Glucagon was never in that system: the 503A nomination track exists for bulk substances that are neither the subject of a USP monograph nor a component of an FDA-approved drug, and glucagon is a component of several. Categorical silence here is neither permission nor a safety finding, and it is not a gap in FDA's evaluation.", "source": { "url": "https://www.fda.gov/media/94155/download", "title": "Bulk Drug Substances Nominated for Use in Compounding Under Section 503A of the Federal Food, Drug, and Cosmetic Act", "publisher": "FDA", "date": "2026-05-14" }, "verifiedAt": "2026-08-02" }, { "finding": "FDA-approved labeling for GVOKE states that hepatic stores of glycogen are necessary for glucagon to produce an antihypoglycemic effect, and describes glucagon's extrahepatic effects as relaxation of the smooth muscle of the stomach, duodenum, small bowel and colon.", "note": "Both approved indications fall out of these two sentences, which is why the label's mechanism section is worth quoting in full. The hepatic action is the rescue indication; the extrahepatic smooth-muscle action is the radiology indication. The first sentence is also the direct source of the efficacy limitation recorded under safety signals: a patient with depleted hepatic glycogen has nothing for the drug to act on.", "source": { "url": "https://www.accessdata.fda.gov/spl/data/8c693dd2-e196-41fe-bd0f-584c1254174c/8c693dd2-e196-41fe-bd0f-584c1254174c.xml", "title": "GVOKE (glucagon) injection and GVOKE VialDx (glucagon) injection — Highlights of Prescribing Information (SPL)", "publisher": "FDA", "date": "2025-12-23", "quote": "Glucagon increases blood glucose concentration by activating hepatic glucagon receptors, thereby stimulating glycogen breakdown and release of glucose from the liver. Hepatic stores of glycogen are necessary for glucagon to produce an antihypoglycemic effect. Extrahepatic effects of glucagon include relaxation of the smooth muscle of the stomach, duodenum, small bowel, and colon." }, "verifiedAt": "2026-08-02" } ], "safetySignals": [ { "signal": "Labeled lack of efficacy in patients with decreased hepatic glycogen. FDA-approved labeling for BAQSIMI states it is effective in treating hypoglycemia only if sufficient hepatic glycogen is present, and that patients in states of starvation, with adrenal insufficiency or chronic hypoglycemia may not have adequate levels of hepatic glycogen for it to be effective. The GVOKE label carries the same limitation for subcutaneous use.", "note": "A labeled failure mode, not a side effect, and the populations it names are exactly the ones most likely to be hypoglycaemic in the first place. The label's instruction in those conditions is to give glucose instead. This is the clearest case on the site of an approved drug whose label states in advance the circumstances in which it will not work.", "source": { "url": "https://www.accessdata.fda.gov/spl/data/54988ebe-c60f-a434-e063-6394a90a20d5/54988ebe-c60f-a434-e063-6394a90a20d5.xml", "title": "BAQSIMI (glucagon) nasal powder — Highlights of Prescribing Information (SPL)", "publisher": "FDA", "date": "2026-06-19", "quote": "BAQSIMI is effective in treating hypoglycemia only if sufficient hepatic glycogen is present. Patients in states of starvation, with adrenal insufficiency or chronic hypoglycemia may not have adequate levels of hepatic glycogen for BAQSIMI to be effective. Patients with these conditions should be treated with glucose." }, "verifiedAt": "2026-08-02" }, { "signal": "Contraindicated in pheochromocytoma, because of the risk of a substantial increase in blood pressure from catecholamine release; contraindicated in insulinoma, because of the risk of hypoglycemia; and contraindicated in patients with prior hypersensitivity reaction to glucagon or to the product's excipients. GVOKE VialDx used as a diagnostic aid is additionally contraindicated in glucagonoma.", "note": "Two of these are paradoxical and worth stating plainly. In insulinoma the label records that glucagon administration may produce an initial rise in blood glucose but may then stimulate exaggerated insulin release and cause hypoglycemia — a hyperglycaemic agent producing the condition it is given to reverse. In glucagonoma the diagnostic use may cause secondary hypoglycemia. These are screening questions a prescriber asks, and the identical contraindications appear on the BAQSIMI label.", "source": { "url": "https://www.accessdata.fda.gov/spl/data/8c693dd2-e196-41fe-bd0f-584c1254174c/8c693dd2-e196-41fe-bd0f-584c1254174c.xml", "title": "GVOKE (glucagon) injection and GVOKE VialDx (glucagon) injection — Highlights of Prescribing Information (SPL)", "publisher": "FDA", "date": "2025-12-23", "quote": "GVOKE and GVOKE VialDx are contraindicated in patients with: Pheochromocytoma because of the risk of substantial increase in blood pressure … Insulinoma because of the risk of hypoglycemia … Prior hypersensitivity reaction to glucagon or to any of the excipients in GVOKE or GVOKE VialDx. … GVOKE VialDx for use as a diagnostic aid is also contraindicated in patients with glucagonoma because of risk of hypoglycemia" }, "verifiedAt": "2026-08-02" }, { "signal": "Serious hypersensitivity reactions have been reported with glucagon products, including generalized rash and, in some cases, anaphylactic shock with breathing difficulties and hypotension.", "note": "Recorded because 'it is a hormone your body already makes' is the standard reassurance attached to endogenous compounds across this market, and it does not follow. The same warning appears verbatim on the BAQSIMI label. Endogenous identity is not a safety argument: insulin is endogenous too.", "source": { "url": "https://www.accessdata.fda.gov/spl/data/8c693dd2-e196-41fe-bd0f-584c1254174c/8c693dd2-e196-41fe-bd0f-584c1254174c.xml", "title": "GVOKE (glucagon) injection and GVOKE VialDx (glucagon) injection — Highlights of Prescribing Information (SPL)", "publisher": "FDA", "date": "2025-12-23", "quote": "Serious hypersensitivity reactions have been reported with glucagon products, including generalized rash, and in some cases anaphylactic shock with breathing difficulties and hypotension." }, "verifiedAt": "2026-08-02" }, { "signal": "Necrolytic migratory erythema, a skin rash, has been reported postmarketing following continuous glucagon infusion and resolved with discontinuation of the glucagon. FDA approved labeling states GVOKE and GVOKE VialDx are not approved for continuous infusion.", "note": "The one labeled signal attached to a mode of use that is outside the approval. The approved products are single-administration rescue or a single diagnostic administration; the reported rash follows continuous infusion, which the label expressly states is not an approved use of these products. Anyone reasoning from 'glucagon is well characterised in humans' toward sustained or repeated exposure is reasoning past the evidence base recorded here, all of which is single-administration.", "source": { "url": "https://www.accessdata.fda.gov/spl/data/8c693dd2-e196-41fe-bd0f-584c1254174c/8c693dd2-e196-41fe-bd0f-584c1254174c.xml", "title": "GVOKE (glucagon) injection and GVOKE VialDx (glucagon) injection — Highlights of Prescribing Information (SPL)", "publisher": "FDA", "date": "2025-12-23", "quote": "Necrolytic Migratory Erythema (NME): a skin rash, has been reported postmarketing following continuous glucagon infusion and resolved with discontinuation of the glucagon. GVOKE and GVOKE VialDx are not approved for continuous infusion." }, "verifiedAt": "2026-08-02" }, { "signal": "Labeled warnings specific to intravenous diagnostic use of GVOKE VialDx include hyperglycemia in patients with diabetes mellitus, and increases in myocardial oxygen demand, blood pressure and pulse rate in patients with cardiac disease, for whom cardiac monitoring is recommended.", "note": "Route- and indication-specific, and recorded separately for that reason: these warnings attach to the intravenous diagnostic presentation, not to the subcutaneous rescue presentations. Note the direction of the first one — the product given to raise blood glucose in an emergency is warned, in its diagnostic role, for raising blood glucose too much in the same patient population.", "source": { "url": "https://www.accessdata.fda.gov/spl/data/8c693dd2-e196-41fe-bd0f-584c1254174c/8c693dd2-e196-41fe-bd0f-584c1254174c.xml", "title": "GVOKE (glucagon) injection and GVOKE VialDx (glucagon) injection — Highlights of Prescribing Information (SPL)", "publisher": "FDA", "date": "2025-12-23", "quote": "Hyperglycemia with Intravenous Use as a Diagnostic Aid in Patients with Diabetes Mellitus: GVOKE VialDx in patients with diabetes mellitus may cause hyperglycemia. … Blood Pressure and Heart Rate Increases with Intravenous Use as a Diagnostic Aid in Patients with Cardiac Disease: GVOKE VialDx may increase myocardial oxygen demand, blood pressure, and pulse rate. Cardiac monitoring is recommended in patients with cardiac disease during use of GVOKE VialDx as a diagnostic aid" }, "verifiedAt": "2026-08-02" }, { "signal": "The most common adverse reactions reported at an incidence of 10% or greater in BAQSIMI trials were nausea, vomiting, headache, upper respiratory tract irritation (rhinorrhea, nasal discomfort, nasal congestion, cough and epistaxis), watery eyes, redness of eyes, and itchy nose, throat and eyes.", "note": "Reproduced because the nasal route is frequently described as the gentler option and the label does not support that framing. In the pooled adult trials the label reports nausea in 26 percent, headache in 18 percent and vomiting in 15 percent of BAQSIMI recipients; among solicited symptoms, 59 percent reported an increase in watery eyes and 43 percent in nasal congestion. These are percentages of participants reporting a reaction, not amounts of anything.", "source": { "url": "https://www.accessdata.fda.gov/spl/data/54988ebe-c60f-a434-e063-6394a90a20d5/54988ebe-c60f-a434-e063-6394a90a20d5.xml", "title": "BAQSIMI (glucagon) nasal powder — Highlights of Prescribing Information (SPL)", "publisher": "FDA", "date": "2026-06-19", "quote": "Most common (≥10%) adverse reactions associated with BAQSIMI are nausea, vomiting, headache, upper respiratory tract irritation (i.e., rhinorrhea, nasal discomfort, nasal congestion, cough, and epistaxis), watery eyes, redness of eyes, itchy nose, throat and eyes." }, "verifiedAt": "2026-08-02" } ], "faqs": [ { "question": "Is glucagon FDA-approved?", "answer": "Yes. Glucagon is an approved drug, not a research chemical, and it has been approved for a long time — Drugs@FDA records the original Lilly glucagon application, NDA 012122, as approved on 14 November 1960. Twelve applications list glucagon or glucagon hydrochloride as an active ingredient. The ones currently recorded as marketed are NDA 212097 (Gvoke HypoPen, Gvoke PFS and Gvoke Kit, from Xeris), NDA 210134 (Baqsimi nasal powder, from Amphastar), NDA 201849 (Glucagon for Injection, from Fresenius Kabi) and four abbreviated applications from Mylan, Amphastar, Lupin and Cipla. Several are recorded as Discontinued, including Eli Lilly's two glucagon NDAs and Novo Nordisk's GlucaGen. A caution for anyone checking this themselves: querying the openFDA Drugs@FDA endpoint by generic name returns only seven of the twelve applications, because the openfda block is empty on five of them, including the 1960 approval. Query by active ingredient instead.", "source": { "url": "https://api.fda.gov/drug/drugsfda.json?search=products.active_ingredients.name:%22GLUCAGON%22&limit=100", "title": "Drugs@FDA — applications with glucagon or glucagon hydrochloride as an active ingredient", "publisher": "FDA", "date": "2026-07-31" }, "verifiedAt": "2026-08-02" }, { "question": "What is glucagon actually approved to treat?", "answer": "Two things, and they are less alike than they sound. The first is emergency treatment of severe hypoglycemia in patients with diabetes. The second is diagnostic: FDA has approved glucagon as a gastrointestinal motility inhibitor, given during radiologic examinations to temporarily stop the gut moving so it can be imaged. The GVOKE label states both: 'GVOKE is indicated for subcutaneous use for the treatment of severe hypoglycemia in adult and pediatric patients aged two and older with diabetes' and 'GVOKE VialDx is indicated for intravenous use as a diagnostic aid during radiologic examinations to temporarily inhibit movement of the gastrointestinal tract in adult patients.' Both fall directly out of the label's mechanism section, which states that glucagon raises blood glucose by activating hepatic glucagon receptors and that its extrahepatic effects include relaxation of the smooth muscle of the stomach, duodenum, small bowel and colon. Baqsimi carries only the hypoglycemia indication; the Fresenius Kabi presentations under NDA 201849 carry one or both depending on the presentation.", "source": { "url": "https://www.accessdata.fda.gov/spl/data/8c693dd2-e196-41fe-bd0f-584c1254174c/8c693dd2-e196-41fe-bd0f-584c1254174c.xml", "title": "GVOKE (glucagon) injection and GVOKE VialDx (glucagon) injection — Highlights of Prescribing Information (SPL)", "publisher": "FDA", "date": "2025-12-23", "quote": "1.1 Severe Hypoglycemia in Adult and Pediatric Patients Aged 2 Years and Older with Diabetes GVOKE is indicated for subcutaneous use for the treatment of severe hypoglycemia in adult and pediatric patients aged two and older with diabetes. 1.2 Diagnostic Aid in Adults GVOKE VialDx is indicated for intravenous use as a diagnostic aid during radiologic examinations to temporarily inhibit movement of the gastrointestinal tract in adult patients." }, "verifiedAt": "2026-08-02" }, { "question": "Is glucagon approved for weight loss or fat burning?", "answer": "No. No FDA-approved glucagon label read for this record contains a weight, body composition or metabolic-enhancement indication. Every approved indication across the current labels is one of two things — treating severe hypoglycemia in patients with diabetes, or acting as a diagnostic aid during radiologic examinations to temporarily inhibit movement of the gastrointestinal tract. Worth separating two distinct things that share a word: glucagon-receptor agonism is one arm of several investigational multi-agonist obesity drugs, but those are different molecules with their own development programmes and their own regulatory status, and nothing about them transfers to the approved glucagon products. The clinical evidence behind the approved products is also specific to the approved use: the pivotal trials tested reversal of insulin-induced hypoglycaemia against another glucagon injection, and none of them studied weight or body composition. Note also that the approved rescue products are labeled for single emergency administration, and their labeling states they are not approved for continuous infusion.", "source": { "url": "https://www.accessdata.fda.gov/spl/data/3d6add4a-5d95-4e63-9761-7e97a92137ba/3d6add4a-5d95-4e63-9761-7e97a92137ba.xml", "title": "Glucagon for Injection (severe hypoglycemia and diagnostic aid presentation, NDA 201849) — Highlights of Prescribing Information (SPL)", "publisher": "FDA", "date": "2025-03-31", "quote": "Glucagon for Injection is an antihypoglycemic agent and a gastrointestinal motility inhibitor indicated: for the treatment of severe hypoglycemia in pediatric and adult patients with diabetes (1.1) as a diagnostic aid for use during radiologic examinations to temporarily inhibit movement of the gastrointestinal tract in adult patients (1.2)" }, "verifiedAt": "2026-08-02" }, { "question": "Can any product labeled 'Glucagon for Injection' be used to treat severe hypoglycemia?", "answer": "No, and this is the trap on this compound. Under one application number — NDA 201849, Fresenius Kabi — there are two presentations of Glucagon for Injection with different approved indications. One is approved for both severe hypoglycemia and diagnostic use. The other is approved only as a diagnostic aid, and its FDA-approved labeling carries an explicit Limitation of Use: 'Glucagon for Injection is not indicated for the emergency treatment of hypoglycemia because it is not packaged with a syringe and diluent necessary for rapid preparation and administration during an emergency outside of a healthcare facility.' The reason FDA gives is about packaging rather than pharmacology — the diagnostic presentation is not supplied with what someone would need to prepare and give it in an emergency. The generic name on the carton does not distinguish the two, so the indication section of the specific product's labeling is the only thing that answers the question.", "source": { "url": "https://www.accessdata.fda.gov/spl/data/9e17207f-b348-4be8-8416-2f0aa1392390/9e17207f-b348-4be8-8416-2f0aa1392390.xml", "title": "Glucagon for Injection (diagnostic aid presentation, NDA 201849) — Highlights of Prescribing Information (SPL)", "publisher": "FDA", "date": "2022-04-01", "quote": "Limitations of Use: Glucagon for Injection is not indicated for the emergency treatment of hypoglycemia because it is not packaged with a syringe and diluent necessary for rapid preparation and administration during an emergency outside of a healthcare facility." }, "verifiedAt": "2026-08-02" }, { "question": "Does glucagon always work for severe hypoglycemia?", "answer": "No — FDA-approved labeling names in advance the circumstances in which it will not. The BAQSIMI label states: 'BAQSIMI is effective in treating hypoglycemia only if sufficient hepatic glycogen is present. Patients in states of starvation, with adrenal insufficiency or chronic hypoglycemia may not have adequate levels of hepatic glycogen for BAQSIMI to be effective. Patients with these conditions should be treated with glucose.' The GVOKE label carries the same limitation for subcutaneous use. The mechanism explains it: glucagon raises blood glucose by activating hepatic glucagon receptors and stimulating glycogen breakdown, so a patient whose liver glycogen is already depleted has nothing for the drug to act on. Separately, the products are contraindicated in pheochromocytoma, because glucagon can stimulate catecholamine release from the tumour, and in insulinoma, where labeling records that an initial rise in blood glucose may be followed by exaggerated insulin release and hypoglycemia.", "source": { "url": "https://www.accessdata.fda.gov/spl/data/54988ebe-c60f-a434-e063-6394a90a20d5/54988ebe-c60f-a434-e063-6394a90a20d5.xml", "title": "BAQSIMI (glucagon) nasal powder — Highlights of Prescribing Information (SPL)", "publisher": "FDA", "date": "2026-06-19", "quote": "BAQSIMI is effective in treating hypoglycemia only if sufficient hepatic glycogen is present. Patients in states of starvation, with adrenal insufficiency or chronic hypoglycemia may not have adequate levels of hepatic glycogen for BAQSIMI to be effective. Patients with these conditions should be treated with glucose." }, "verifiedAt": "2026-08-02" }, { "question": "Are Baqsimi and Gvoke the same thing?", "answer": "No. They are the same active ingredient in different products, approved under different applications, and their labeling differs in ways that matter at the point of use. BAQSIMI (NDA 210134, Amphastar) is a nasal powder, and its label indicates it 'for the treatment of severe hypoglycemia in adults and pediatric patients aged 1 year and older with diabetes' — a hypoglycemia indication only. GVOKE (NDA 212097, Xeris) is a subcutaneous injection indicated from age two, and the same application also covers GVOKE VialDx, an intravenous presentation approved for a completely different purpose: use as a diagnostic aid during radiologic examinations. So the paediatric age floors differ, the routes differ, and only one of the two applications carries a diagnostic indication. Drugs@FDA also records the GVOKE VialDx presentation as Discontinued.", "source": { "url": "https://www.accessdata.fda.gov/spl/data/54988ebe-c60f-a434-e063-6394a90a20d5/54988ebe-c60f-a434-e063-6394a90a20d5.xml", "title": "BAQSIMI (glucagon) nasal powder — Highlights of Prescribing Information (SPL)", "publisher": "FDA", "date": "2026-06-19", "quote": "BAQSIMI is an antihypoglycemic agent indicated for the treatment of severe hypoglycemia in adults and pediatric patients aged 1 year and older with diabetes." }, "verifiedAt": "2026-08-02" }, { "question": "Is glucagon on FDA's 503A bulk drug substances list?", "answer": "No. Glucagon appears in none of Categories 1, 2 or 3 of FDA's 503A bulk drug substances list updated 14 May 2026, verified by fetching the document and text-extracting it directly on 2 August 2026. That absence means something different from the absence of the compounds this site usually covers. BPC-157 and the other consumer peptides are absent because their nominations were withdrawn, and they remain unusable in 503A compounding. Glucagon was never in that process: the 503A nomination track exists for bulk substances that are neither the subject of a USP monograph nor a component of an FDA-approved drug, and glucagon is a component of several currently marketed approved drugs. Silence in the categories here is neither a permission nor a safety finding, and this record deliberately records no 503A category for glucagon rather than assert a status in a proceeding it was never part of.", "source": { "url": "https://www.fda.gov/media/94155/download", "title": "Bulk Drug Substances Nominated for Use in Compounding Under Section 503A of the Federal Food, Drug, and Cosmetic Act", "publisher": "FDA", "date": "2026-05-14" }, "verifiedAt": "2026-08-02" } ] }, { "slug": "gonadorelin", "name": "Gonadorelin", "aliases": [ "GnRH", "gonadotropin-releasing hormone", "LHRH", "luteinizing hormone-releasing hormone", "gonadorelin hydrochloride", "gonadorelin acetate", "Factrel", "Lutrepulse" ], "url": "https://peptides101.com/compounds/gonadorelin", "moleculeNote": "Gonadorelin is the synthetic form of the native hypothalamic decapeptide itself, not an analogue of it. The FDA-approved veterinary labeling states that gonadorelin 'is the gonadotropin releasing hormone (GnRH) which is produced by the hypothalamus' and that the product 'has the identical amino acid sequence as endogenous gonadorelin'. TWO DISAMBIGUATIONS, both of which change what a claim means. (1) SALT FORM AND APPLICATION. The two human applications are not the same product: NDA 018123 (Factrel) contains gonadorelin hydrochloride, NDA 019687 (Lutrepulse Kit) contains gonadorelin acetate. They were approved seven years apart by different sponsors under different submission classifications. Anything true of one is not automatically true of the other. (2) GONADORELIN IS NOT A GnRH AGONIST ANALOGUE. Leuprolide, goserelin and triptorelin are modified, long-acting GnRH analogues with their own approvals and their own labeled effects; gonadorelin is the short-lived natural sequence. Evidence and approvals attaching to those molecules do not transfer to this one, in either direction. A third collision is purely a naming problem but trips people constantly: 'Factrel' is also the brand name of a currently marketed FDA-approved ANIMAL drug for cattle (NADA 139-237). A search for Factrel labeling returns that product, not the human one.", "quickAnswer": "Gonadorelin, the synthetic form of gonadotropin-releasing hormone (GnRH), is the active ingredient of two FDA-approved new drug applications — Factrel (gonadorelin hydrochloride, NDA 018123, approved 1982-09-30) and Lutrepulse Kit (gonadorelin acetate, NDA 019687, approved 1989-10-10) — and Drugs@FDA lists every product under both applications in marketing status Discontinued, so no approved gonadorelin product for human use is marketed in the United States. No Federal Register notice withdrawing either approval was found, which is why this record says discontinued rather than withdrawn. FDA has not published the approved labeling for either application — Drugs@FDA states 'Label is not available on this site.' for every submission on both — so the approved indications are recorded here as a blank rather than taken from secondary sources. The only gonadorelin labeling FDA currently publishes belongs to approved ANIMAL drugs for cattle, one of which is also branded Factrel and states 'For use in animals only. Not for human use.' Gonadorelin appears in none of the three categories of FDA's 503A bulk drug substances list updated 2026-05-14. On 17 June 2026 FDA issued warning letter 729447 to Wholesale Peptide stating that its 'Gonadorelin' product is an unapproved new drug under section 505(a) of the FD&C Act.", "fdaStatus": { "value": "approved", "note": "READ THIS ONE CAREFULLY, BECAUSE THE LABEL ON THE BADGE IS THE LEAST PRECISE THING ABOUT IT. Gonadorelin is the active ingredient of two FDA-approved new drug applications, and NEITHER HAS A MARKETED PRODUCT. Drugs@FDA lists all five products across the two applications — three Factrel presentations under NDA 018123 (original approval 1982-09-30, classification 'Type 1 - New Molecular Entity', sponsor now Hikma) and two Lutrepulse Kit presentations under NDA 019687 (original approval 1989-10-10, classification 'Type 2 - New Active Ingredient', review priority 'STANDARD; Orphan', sponsor Ferring) — every one of them in marketing status Discontinued. WHY NOT `approval-withdrawn`, WHICH IS WHAT THIS RECORD WAS EXPECTED TO SAY. Because discontinuation from marketing and withdrawal of approval are different acts and only the first is documented. Withdrawal under 21 CFR 314.150(c) requires the applicant to REQUEST it, and FDA announces such withdrawals in the Federal Register. A full-text search of FDA's Federal Register documents for 'gonadorelin' returns seventeen documents, all of them NEW ANIMAL DRUG notices; 'Lutrepulse' returns zero across the entire Federal Register; and the NDA numbers return nothing. Both applications also remain in the Orange Book's Discontinued Drug Product List as of the data file read on 2026-08-02. This is the compound where sermorelin's pattern does NOT repeat: sermorelin's GEREF NDAs have an actual withdrawal notice (74 FR 23407), and gonadorelin's do not. THE LIMIT OF THAT REASONING, stated rather than hidden. It is negative evidence. The Federal Register's full-text index begins in 1994. For NDA 018123 that gap cannot matter — FDA approved a supplement to it in July 2002, so any withdrawal is necessarily inside the indexed period. For NDA 019687 the last recorded FDA action is 1993-12-02, leaving a theoretical four-week window at the end of 1993. And FDA's own Orange Book preface says the Discontinued list can include products that 'have had their approvals withdrawn for other than safety or effectiveness reasons subsequent to being discontinued from marketing', so presence on that list is corroborating rather than conclusive. If a withdrawal notice for either application surfaces, this field becomes `approval-withdrawn` and the note becomes the correction. WHAT NOBODY SHOULD TAKE FROM THE WORD `approved`: that an approved gonadorelin product for human use can be obtained. None is marketed, none is listed in the NDC directory as a finished human drug, and FDA has not published the approved labeling for either application.", "source": { "url": "https://api.fda.gov/drug/drugsfda.json?search=products.active_ingredients.name:\"GONADORELIN\"&limit=20", "title": "Drugs@FDA — applications containing gonadorelin (openFDA drug/drugsfda)", "publisher": "FDA", "date": "2026-07-31", "quote": "\"application_number\": \"NDA018123\" … \"brand_name\": \"FACTREL\" … \"name\": \"GONADORELIN HYDROCHLORIDE\" … \"marketing_status\": \"Discontinued\" … \"application_number\": \"NDA019687\" … \"brand_name\": \"LUTREPULSE KIT\" … \"name\": \"GONADORELIN ACETATE\" … \"marketing_status\": \"Discontinued\"" }, "verifiedAt": "2026-08-02" }, "compoundingStatus": null, "evidence": { "tier": "verification-pending", "pendingReason": "Not assigned, and the reason is specific rather than a shrug. The normal shortcut for an FDA-approved drug is to read the pivotal trials out of the label — here that shortcut does not exist, because THE LABEL DOES NOT EXIST IN PUBLIC. Drugs@FDA returns 'Label is not available on this site.' against the 1982 original approval of NDA 018123 and against every one of its fourteen supplements, and the same against the 1989 original approval of NDA 019687 and all of its supplements. Checked on 2026-08-02: openFDA's drug/label endpoint returns NOT_FOUND for both application numbers and for the substance names, DailyMed holds no human gonadorelin SPL (its five gonadorelin labels are all animal drugs), and no label PDF exists for either application under accessdata.fda.gov/drugsatfda_docs/label. So we cannot name the pivotal trials, which means we cannot open them, which means we cannot run the administration check this site requires before assigning any tier. There is a large published human literature in which GnRH was administered to people, and on its face gonadorelin looks like an easy 'proven-in-humans'. It is not being assigned on its face. An approval is evidence that FDA once saw adequate and well-controlled evidence for a SPECIFIC indication in a SPECIFIC population, and with the indication itself unrecoverable there is nothing here to scope a tier to. The blank is the honest answer until the pivotal studies are identified and opened one by one." }, "fdaApproval": { "applicationNumber": "NDA 018123 (Factrel, gonadorelin hydrochloride, sponsor Hikma, approved 1982-09-30); NDA 019687 (Lutrepulse Kit, gonadorelin acetate, sponsor Ferring, approved 1989-10-10)", "brandName": "Factrel, Lutrepulse Kit", "approvedIndication": "NOT RECOVERABLE FROM A PRIMARY SOURCE — recorded as a sourced blank rather than filled in from drug-reference sites. FDA has not published the approved labeling for either application. The Drugs@FDA record for NDA 018123 states, verbatim, 'Label is not available on this site.' against the original 1982 approval and against every one of its fourteen supplements, and the record for NDA 019687 states the same against its original 1989 approval and all of its supplements. What Drugs@FDA does record is the product identity and history: FACTREL, gonadorelin hydrochloride, INJECTABLE;INJECTION, three presentations, marketing status Discontinued, original approval 09/30/1982, submission classification 'Type 1 - New Molecular Entity', review priority PRIORITY; and LUTREPULSE KIT, gonadorelin acetate, INJECTABLE;INJECTION, two presentations, marketing status Discontinued, original approval 10/10/1989, classification 'Type 2 - New Active Ingredient', review priority 'STANDARD; Orphan'. The indications repeated across the secondary corpus for both products may well be accurate; they are not sourced to FDA, and this record will not quote them as if they were.", "discontinued": true, "discontinuedNote": "Discontinued from marketing, which is NOT the same as withdrawn from approval. No Federal Register notice withdrawing either approval was found (see the fdaStatus note for the search and its limits). FDA's Orange Book preface describes the Discontinued Drug Product List as covering approved products that 'have never been marketed, are for exportation, are for military use, have been discontinued from marketing and we have not determined that they were withdrawn from sale for safety or effectiveness reasons, or have had their approvals withdrawn for other than safety or effectiveness reasons subsequent to being discontinued from marketing' — a list that deliberately mixes several situations, so membership in it is corroboration and not proof. Nothing in any document read for this record attributes either discontinuation to a safety or effectiveness finding; equally, no FDA determination to that effect was found, and the preface notes such determinations are only reflected in the Orange Book from 1995 onward. A discontinuation with no stated reason is a blank, not an endorsement.", "source": { "url": "https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=018123", "title": "Drugs@FDA: FDA-Approved Drugs — New Drug Application (NDA) 018123, FACTREL", "publisher": "FDA", "date": "2002-07-19", "quote": "Label is not available on this site." }, "verifiedAt": "2026-08-02" }, "fdaFindings": [ { "finding": "FDA has stated that the product sold as 'Gonadorelin' by Wholesale Peptide is an unapproved new drug under section 505(a) of the FD&C Act, and that introducing or delivering it for introduction into interstate commerce violates sections 301(d) and 505(a).", "note": "The reasoning matters more than the conclusion, and it is the reasoning that generalises past this one seller. FDA's finding is not that the molecule is unapproved in the abstract — it is that THIS PRODUCT is a new drug, because the seller's own website made it one. FDA's stated basis is that the products 'are intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease, and/or intended to affect the structure or any function of the body', citing the intended-use regulation at 21 CFR 201.128, and that 'No approved applications pursuant to section 505 of the FD&C Act … are in effect for these products'. Read that last clause precisely: it is about the seller's products, not about the substance. Two approved applications containing gonadorelin do exist, as this record documents — but an approval covers the product described in the application, not every vial that shares an ingredient name. That is the same structure as the salt-form and research-vial problems elsewhere on this site.", "source": { "url": "https://www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/warning-letters/wholesale-peptide-729447-06172026", "title": "Wholesale Peptide — Warning Letter, reference number 729447", "publisher": "FDA", "date": "2026-06-17", "quote": "Based on our review, “Prostamax” and “Gonadorelin” are unapproved new drugs under section 505(a) of the Federal Food, Drug, and Cosmetic Act (FD&C Act), 21 U.S.C. 355(a). As explained further below, introducing or delivering these products for introduction into interstate commerce violates sections 301(d) and 505(a) of the FD&C Act, 21 U.S.C. 331(d) and 355(a)." }, "verifiedAt": "2026-08-02" }, { "finding": "FDA identified statements on the seller's own gonadorelin product page as evidence of intended use, including: 'Spermatogenesis Research: Investigations show how gonadorelin affects testosterone production and supports testes function in experimental subjects.' and a passage describing exploration of 'applications in cancer research, particularly in hormone-dependent cancers'.", "note": "Recorded because it documents what actually triggered the letter, and because the phrasing is instructive. The page was written in a research-literature register — 'investigations', 'experimental subjects', 'laboratory settings' — and FDA reproduced it as the evidence of intended use anyway. The research voice is the exhibit, not the defence. This is the third time in 2026 that FDA has declined to treat research framing as a disclaimer that changes what a product is.", "source": { "url": "https://www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/warning-letters/wholesale-peptide-729447-06172026", "title": "Wholesale Peptide — Warning Letter, reference number 729447", "publisher": "FDA", "date": "2026-06-17", "quote": "“Spermatogenesis Research: Investigations show how gonadorelin affects testosterone production and supports testes function in experimental subjects.”" }, "verifiedAt": "2026-08-02" }, { "finding": "The Drugs@FDA record for NDA 019687 (Lutrepulse Kit, gonadorelin acetate) states 'Label is not available on this site.' against the original 1989 approval and against every supplement, and lists both products in marketing status Discontinued.", "note": "The second application's page, recorded separately so the record's two-application framing is carried by two documents rather than one. Two details on this page are worth keeping: the original approval is classified 'Type 2 - New Active Ingredient' and its review priority line reads 'STANDARD; Orphan', which is FDA recording an orphan designation on the application. An orphan designation is a statement about the size of the treated population, not about the strength of the evidence.", "source": { "url": "https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=019687", "title": "Drugs@FDA: FDA-Approved Drugs — New Drug Application (NDA) 019687, LUTREPULSE KIT", "publisher": "FDA", "date": "1993-12-02", "quote": "Label is not available on this site." }, "verifiedAt": "2026-08-02" }, { "finding": "Gonadorelin appears in none of Categories 1, 2 or 3 of FDA's list of bulk drug substances nominated for use in compounding under section 503A, updated 2026-05-14.", "note": "Verified by downloading the PDF with a browser user-agent and extracting the text locally on 2026-08-02: zero hits for 'gonadorelin', and zero for 'GnRH', 'gonadotropin' and 'luteinizing' as well, so it is not hiding under a synonym. Recorded to close a misreading rather than to assert a status, and the misreading runs in BOTH directions here. Absence from this list is not permission and it is not a safety finding. It is also not a prohibition: the 503A bulks list is only the THIRD of three statutory routes for a bulk drug substance, and it is reached only when the first two do not apply — see the next finding, where FDA states the sequence in its own words. Gonadorelin's absence here means something categorically different from BPC-157's absence, which followed a withdrawn nomination.", "source": { "url": "https://www.fda.gov/media/94155/download", "title": "Bulk Drug Substances Nominated for Use in Compounding Under Section 503A of the Federal Food, Drug, and Cosmetic Act", "publisher": "FDA", "date": "2026-05-14" }, "verifiedAt": "2026-08-02" }, { "finding": "FDA has stated that state-licensed physicians and pharmacists compounding under section 503A may only compound using bulk drug substances that comply with an applicable USP or NF monograph if one exists and the USP chapter on pharmacy compounding; are components of FDA-approved drug products if an applicable USP or NF monograph does not exist; or appear on the 503A bulks list if such a monograph does not exist and the substance is not a component of an FDA-approved drug product.", "note": "Recorded here because it is the finding that makes the approved-versus-withdrawn distinction at the top of this record carry weight rather than being a technicality. The three conditions are SEQUENTIAL, and the second one turns on being a component of an FDA-approved drug product. WHAT THIS RECORD DOES NOT DO IS APPLY THAT TEST. Whether a substance whose only approved products are discontinued is a 'component of an FDA-approved drug product' for this purpose is a question FDA has not answered for gonadorelin in any document found on 2026-08-02, and it is not one an editor should answer on FDA's behalf. Nor is the monograph question resolved here: whether a USP or NF monograph exists for gonadorelin or its salts was not verified, and it is the FIRST condition, so it governs. The whole of what this record establishes is the sequence and the absence from the list. Anyone reading either as a green light or a red light is reading something that is not there. Note also the scope: section 503A concerns compounding by licensed pharmacists and physicians against prescriptions for identified patients. It has nothing to say about the sale of research-labelled vials, which is what the warning letter above is about.", "source": { "url": "https://www.fda.gov/drugs/human-drug-compounding/bulk-drug-substances-used-compounding-under-section-503a-fdc-act", "title": "Bulk Drug Substances Used in Compounding Under Section 503A of the FD&C Act", "publisher": "FDA", "date": "2026-05-14", "quote": "State-licensed physicians and pharmacists that compound under section 503A of the Federal Food, Drug, and Cosmetic Act (FD&C Act) may only compound drug products using bulk drug substances that: Comply with an applicable United States Pharmacopeia (USP) or National Formulary (NF) monograph if one exists, and the USP chapter on pharmacy compounding; Are components of FDA-approved drug products if an applicable USP or NF monograph does not exist; or Appear on FDA's list of bulk drug substances that can be used in compounding (the 503A bulks list) if such a monograph does not exist and the substance is not a component of an FDA-approved drug product." }, "verifiedAt": "2026-08-02" }, { "finding": "The only gonadorelin products with current FDA-approved labeling published in DailyMed are approved ANIMAL drugs — Factrel (Zoetis, NADA 139-237), Cystorelin, Fertagyl, GonaBreed and Ovacyst. The Factrel animal labeling states: 'For use in animals only. Not for human use.'", "note": "The naming collision is not trivia — it is the reason a search for 'Factrel label' returns a cattle drug, and the reason someone can find an FDA-approved gonadorelin label and believe they have found the human one. The animal Factrel labeling is indicated 'For the treatment of ovarian follicular cysts in lactating dairy cows, beef cows, and replacement dairy and beef heifers' and for oestrous synchronisation in dairy cows. It is a different application (a NADA, not an NDA), a different sponsor, a different strength and a different species. The description section of that same label is also the best public FDA statement of what the molecule is, and is quoted in this record's molecule note for exactly that reason — an animal label is a fine source for chemistry and a worthless source for human effects.", "source": { "url": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=1451663c-b85a-4b45-8b27-6d572d0032f9", "title": "FACTREL (gonadorelin hydrochloride) injection, Zoetis Inc. — FDA-approved animal drug labeling", "publisher": "DailyMed (U.S. National Library of Medicine)", "date": "2026-06-18", "quote": "For use in animals only. Not for human use." }, "verifiedAt": "2026-08-02" }, { "finding": "The NDC Directory contains no finished human drug product with the generic name gonadorelin. Every gonadorelin entry is a BULK INGREDIENT listing by an active pharmaceutical ingredient manufacturer, none of which carries an application number.", "note": "Queried on 2026-08-02: thirteen listings, all product type BULK INGREDIENT, from API suppliers including Bachem, Polypeptide Laboratories, Piramal, Aspen Oss, Darmerica and several Chinese manufacturers, with marketing start dates running from 1993 to 2026. TWO OPPOSITE MISREADINGS TO AVOID. This is not evidence that gonadorelin API is approved — an NDC listing is a registration and listing act under section 510, not an approval, and the entries carry no application number precisely because there is no application behind them. Nor is it evidence that the API is illicit; registering and listing is what a compliant supplier is supposed to do. What it establishes is narrower and more useful: a live, FDA-registered supply chain for the raw substance exists in 2026 while no finished human product does.", "source": { "url": "https://api.fda.gov/drug/ndc.json?search=generic_name:\"gonadorelin\"&limit=20", "title": "NDC Directory — listings with generic name gonadorelin (openFDA drug/ndc)", "publisher": "FDA", "date": "2026-07-31" }, "verifiedAt": "2026-08-02" }, { "finding": "FDA describes the Orange Book's Discontinued Drug Product List as 'a cumulative list of approved products that have never been marketed, are for exportation, are for military use, have been discontinued from marketing and we have not determined that they were withdrawn from sale for safety or effectiveness reasons, or have had their approvals withdrawn for other than safety or effectiveness reasons subsequent to being discontinued from marketing'. Both gonadorelin applications appear in that list.", "note": "Recorded because it is the caveat on this record's own central claim, and leaving it in a note would mean asserting a limitation with no document behind it. The Orange Book data file downloaded on 2026-08-02 carries all five gonadorelin products with the DISCN flag: three FACTREL entries under application 018123 (Hikma) and two LUTREPULSE KIT entries under 019687 (Ferring). FDA's own definition of the list mixes several situations, one of which IS a withdrawn approval — so this listing corroborates the `approved` status but cannot establish it alone. The Federal Register search does the load-bearing work; this document says why that second check was necessary. FDA also notes on the same page that Federal Register determinations about whether a product was withdrawn for safety or effectiveness reasons are only reflected in the Orange Book from 1995 onward, so no such annotation appears on these entries either way.", "source": { "url": "https://www.fda.gov/drugs/development-approval-process-drugs/orange-book-preface", "title": "Orange Book Preface — Approved Drug Products with Therapeutic Equivalence Evaluations", "publisher": "FDA", "date": "2026-01-15", "quote": "a cumulative list of approved products that have never been marketed, are for exportation, are for military use, have been discontinued from marketing and we have not determined that they were withdrawn from sale for safety or effectiveness reasons, or have had their approvals withdrawn for other than safety or effectiveness reasons subsequent to being discontinued from marketing (Discontinued Drug Product List)." }, "verifiedAt": "2026-08-02" }, { "finding": "Under 21 CFR 314.150(c), FDA withdraws approval of an application because a drug is no longer being marketed only when the APPLICANT REQUESTS that withdrawal: 'FDA will withdraw approval of an application or abbreviated application if the applicant requests its withdrawal because the drug subject to the application or abbreviated application is no longer being marketed…'", "note": "The regulation that makes 'discontinued' and 'withdrawn' genuinely different rather than two words for the same event. Withdrawal is an affirmative act with a trigger — an applicant's written request — and it does not follow automatically from a product leaving the market. That is why this record treats the absence of a withdrawal notice as meaningful rather than as a filing gap. Note the last clause of the quoted sentence, which is doing quiet work: this route is available only when none of the safety or effectiveness grounds in paragraphs (a) and (b) applies. The same section elsewhere provides that where FDA and an applicant agree to a withdrawal, the agency withdraws approval 'in a notice published in the Federal Register'. `date` on this source is the section's last amendment (64 FR 402, Jan. 5, 1999), not the date we read it.", "source": { "url": "https://www.ecfr.gov/current/title-21/chapter-I/subchapter-D/part-314/subpart-D/section-314.150", "title": "21 CFR 314.150 — Withdrawal of approval of an application or abbreviated application", "publisher": "Office of the Federal Register (eCFR)", "date": "1999-01-05", "quote": "FDA will withdraw approval of an application or abbreviated application if the applicant requests its withdrawal because the drug subject to the application or abbreviated application is no longer being marketed, provided none of the conditions listed in paragraphs (a) and (b) of this section applies to the drug." }, "verifiedAt": "2026-08-02" }, { "finding": "FDA approved a supplement to NDA 018123 (Factrel, gonadorelin HCl) on 19 July 2002, twenty years after the original approval, stating: 'We have completed the review of this supplemental application, and it is approved.'", "note": "A small document with one important job on this record: it fixes a floor under the search window. NDA 018123 was demonstrably an approved application in July 2002, so any withdrawal of it must postdate 2002 — which places it inside the Federal Register's full-text index, where nothing was found. Without this letter the negative search result would be much weaker, because a pre-1994 withdrawal could not be ruled out. The letter also records the details Drugs@FDA compresses: the applicant was Wyeth Pharmaceuticals, the supplement covered a change in the site of manufacture, packaging, testing and release of the diluent, and the review sat with the Division of Reproductive and Urologic Drug Products. The same reasoning is NOT available for NDA 019687, whose last recorded action is 1993-12-02.", "source": { "url": "https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2002/18123scs014ltr.pdf", "title": "NDA 18-123/SCS-014 approval letter, Factrel (gonadorelin HCl)", "publisher": "FDA", "date": "2002-07-19", "quote": "We have completed the review of this supplemental application, and it is approved." }, "verifiedAt": "2026-08-02" } ], "safetySignals": [ { "signal": "FDA has stated that products of this kind are especially concerning from a public health perspective because injectable drug products can pose risks of serious harm to users, since injectables are delivered directly into the body, sometimes directly into the bloodstream, and therefore bypass some of the body's key defenses against toxins and microorganisms that can lead to serious and life-threatening conditions.", "note": "FDA wrote this about the specific products in the letter, one of which was sold as gonadorelin. Note what the concern is ABOUT: it is a route-and-sterility argument, not a pharmacological finding about the molecule. It applies to an unapproved injectable whatever is in the vial, which is the point — with no approval, no label and no released batch record, sterility and identity are assertions by the seller.", "source": { "url": "https://www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/warning-letters/wholesale-peptide-729447-06172026", "title": "Wholesale Peptide — Warning Letter, reference number 729447", "publisher": "FDA", "date": "2026-06-17", "quote": "These products are especially concerning from a public health perspective because injectable drug products can pose risks of serious harm to users. Injectable products are delivered directly into the body, sometimes directly into the bloodstream, and therefore, bypass some of the body's key defenses against toxins and microorganisms that can lead to serious and life-threatening conditions." }, "verifiedAt": "2026-08-02" }, { "signal": "No FDA-approved human prescribing information for gonadorelin is publicly available, so there is no published set of contraindications, warnings, precautions or adverse reactions from either approved application. FDA's Drugs@FDA record returns 'Label is not available on this site.' for every submission on both NDA 018123 and NDA 019687.", "note": "Recorded as a safety signal rather than buried as an administrative footnote, because the absence has a consequence. On every other approved compound in this library the labeled contraindications are the screening questions a purchaser of an unapproved vial is never asked. Here nobody can ask them, because the questions are not published. That is a statement about the public record and not about the molecule: an unavailable label is not evidence of a benign safety profile, and it is not evidence of a bad one either.", "source": { "url": "https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=018123", "title": "Drugs@FDA: FDA-Approved Drugs — New Drug Application (NDA) 018123, FACTREL", "publisher": "FDA", "date": "2002-07-19", "quote": "Label is not available on this site." }, "verifiedAt": "2026-08-02" } ], "faqs": [ { "question": "Is gonadorelin FDA-approved?", "answer": "Yes as a substance, and no as anything you can obtain. Gonadorelin is the active ingredient of two FDA-approved new drug applications — NDA 018123 (Factrel, gonadorelin hydrochloride, approved 30 September 1982, classified by FDA as 'Type 1 - New Molecular Entity', now held by Hikma) and NDA 019687 (Lutrepulse Kit, gonadorelin acetate, approved 10 October 1989, 'Type 2 - New Active Ingredient', held by Ferring). Drugs@FDA lists all five products across those two applications in marketing status Discontinued, so no approved gonadorelin product for human use is marketed in the United States, and the NDC Directory contains no finished human gonadorelin product at all. Two things follow that people routinely get backwards. An approval attaches to the products described in the application, not to every vial sharing the ingredient name — FDA issued a warning letter in June 2026 stating that a product sold online as 'Gonadorelin' was an unapproved new drug. And the existence of an approval says nothing about what the approval was FOR: FDA has not published the labeling for either application, so the approved indications cannot be quoted here.", "source": { "url": "https://api.fda.gov/drug/drugsfda.json?search=products.active_ingredients.name:\"GONADORELIN\"&limit=20", "title": "Drugs@FDA — applications containing gonadorelin (openFDA drug/drugsfda)", "publisher": "FDA", "date": "2026-07-31", "quote": "\"application_number\": \"NDA018123\" … \"brand_name\": \"FACTREL\" … \"marketing_status\": \"Discontinued\" … \"application_number\": \"NDA019687\" … \"brand_name\": \"LUTREPULSE KIT\" … \"marketing_status\": \"Discontinued\"" }, "verifiedAt": "2026-08-02" }, { "question": "What was Factrel approved for, and why can't I find the label?", "answer": "The label is not published by FDA, so this site does not state the indication. Drugs@FDA carries the approval history for NDA 018123 (Factrel, gonadorelin hydrochloride, approved 30 September 1982, fourteen supplements through July 2002) and returns the same line against every one of them: 'Label is not available on this site.' The same is true of NDA 019687 (Lutrepulse Kit). Checked on 2 August 2026, there is also no gonadorelin human label in DailyMed, none in openFDA's drug/label endpoint under either application number, and no label PDF under accessdata.fda.gov/drugsatfda_docs/label. Drug-reference sites do state indications for both products, and they may be right, but they are not FDA and this site does not requote them as though they were. One warning while you search: 'Factrel' is also the brand name of a currently marketed FDA-approved animal drug for cattle, so a search for Factrel labeling will return a document whose own text reads 'For use in animals only. Not for human use.'", "source": { "url": "https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=018123", "title": "Drugs@FDA: FDA-Approved Drugs — New Drug Application (NDA) 018123, FACTREL", "publisher": "FDA", "date": "2002-07-19", "quote": "Label is not available on this site." }, "verifiedAt": "2026-08-02" }, { "question": "Did FDA withdraw approval of gonadorelin?", "answer": "No withdrawal was found, and the distinction matters. Discontinuing a product from marketing and withdrawing an application's approval are separate acts: under 21 CFR 314.150(c) FDA withdraws approval when the applicant REQUESTS withdrawal because the drug is no longer being marketed, and FDA announces such withdrawals in the Federal Register. A full-text search of FDA's Federal Register documents for 'gonadorelin', run on 2 August 2026, returns seventeen documents — every one of them a NEW ANIMAL DRUG notice. 'Lutrepulse' returns zero documents across the entire Federal Register, and the two application numbers return nothing. Both applications also still appear in the Orange Book's Discontinued Drug Product List. The honest limits: this is negative evidence, the Federal Register's full-text index begins in 1994, and FDA's own Orange Book preface says the Discontinued list can include products whose approvals were withdrawn for reasons other than safety or effectiveness. For NDA 018123 the gap cannot matter, because FDA approved a supplement to it in July 2002. This is where gonadorelin differs from sermorelin, whose GEREF approvals have an actual Federal Register withdrawal notice.", "source": { "url": "https://www.federalregister.gov/documents/search?conditions%5Bagencies%5D%5B%5D=food-and-drug-administration&conditions%5Bterm%5D=gonadorelin", "title": "Federal Register full-text search — FDA documents mentioning gonadorelin", "publisher": "Office of the Federal Register", "date": "2026-08-02", "quote": "New Animal Drugs; Approval of New Animal Drug Applications; Withdrawal of Approval of New Animal Drug Applications; Changes of Sponsorship" }, "verifiedAt": "2026-08-02" }, { "question": "Is it legal to buy gonadorelin as a research peptide online?", "answer": "FDA has treated at least one such sale as illegal. In warning letter 729447, issued 17 June 2026 after a review of the seller's website, FDA stated that the product offered as 'Gonadorelin' is an unapproved new drug under section 505(a) of the FD&C Act and that 'introducing or delivering these products for introduction into interstate commerce violates sections 301(d) and 505(a)'. FDA's basis was the seller's own product page: the statements there showed the product was 'intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease, and/or intended to affect the structure or any function of the body', which makes it a drug under section 201(g)(1). Note that the page FDA quoted was written in research language — 'Investigations show how gonadorelin affects testosterone production … in experimental subjects' — and FDA reproduced that language as the evidence rather than accepting it as a disclaimer. FDA also stated 'No approved applications pursuant to section 505 of the FD&C Act … are in effect for these products', which is about the seller's products: two approved applications containing gonadorelin do exist, and neither of them describes a vial bought from a website.", "source": { "url": "https://www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/warning-letters/wholesale-peptide-729447-06172026", "title": "Wholesale Peptide — Warning Letter, reference number 729447", "publisher": "FDA", "date": "2026-06-17", "quote": "Based on our review, “Prostamax” and “Gonadorelin” are unapproved new drugs under section 505(a) of the Federal Food, Drug, and Cosmetic Act (FD&C Act), 21 U.S.C. 355(a)." }, "verifiedAt": "2026-08-02" }, { "question": "Can a compounding pharmacy legally compound gonadorelin?", "answer": "This record does not answer that, and the reason is worth reading, because both confident answers circulating are unsupported. FDA states that a pharmacist or physician compounding under section 503A may use a bulk drug substance only if it, in FDA's own sequence, complies with an applicable USP or NF monograph if one exists; or is a component of an FDA-approved drug product if no such monograph exists; or appears on the 503A bulks list if no monograph exists and it is not a component of an FDA-approved drug product. Two facts are established here: gonadorelin appears in none of the three categories of the 503A bulks list updated 14 May 2026, verified by extracting the document's text on 2 August 2026; and gonadorelin is the active ingredient of two approved NDAs whose products are all discontinued. What is NOT established is how the first two conditions apply — whether a USP or NF monograph exists for gonadorelin or its salts was not verified, and FDA has published no determination on whether a substance whose only approved products are discontinued counts as a component of an FDA-approved drug product. Absence from the bulks list is therefore not a prohibition, because the list is the third route and is reached only if the first two fail. Separately, section 503A is about compounding against prescriptions for identified patients; it has nothing to say about buying a research-labelled vial online.", "source": { "url": "https://www.fda.gov/drugs/human-drug-compounding/bulk-drug-substances-used-compounding-under-section-503a-fdc-act", "title": "Bulk Drug Substances Used in Compounding Under Section 503A of the FD&C Act", "publisher": "FDA", "date": "2026-05-14", "quote": "State-licensed physicians and pharmacists that compound under section 503A of the Federal Food, Drug, and Cosmetic Act (FD&C Act) may only compound drug products using bulk drug substances that: Comply with an applicable United States Pharmacopeia (USP) or National Formulary (NF) monograph if one exists, and the United States Pharmacopeia chapter on pharmacy compounding; Are components of FDA-approved drug products if an applicable USP or NF monograph does not exist; or Appear on FDA's list of bulk drug substances that can be used in compounding (the 503A bulks list) if such a monograph does not exist and the substance is not a component of an FDA-approved drug product." }, "verifiedAt": "2026-08-02" }, { "question": "Is the Factrel sold for cattle the same as human gonadorelin?", "answer": "Same molecule, different drug product, and the labeling says so. The Factrel currently marketed in the United States is an FDA-approved ANIMAL drug from Zoetis under NADA 139-237, indicated 'For the treatment of ovarian follicular cysts in lactating dairy cows, beef cows, and replacement dairy and beef heifers' and for synchronising oestrous cycles in dairy cows. Its labeling states: 'For use in animals only. Not for human use.' The human Factrel is a separate application (NDA 018123, gonadorelin hydrochloride, approved 1982), it is a different sponsor and a different formulation, and Drugs@FDA lists all of its products as Discontinued. The two share a brand name and an active ingredient and nothing else that matters. This is worth knowing because the animal label is the only FDA-approved gonadorelin labeling a member of the public can currently read, which makes it easy to mistake for the human one.", "source": { "url": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=1451663c-b85a-4b45-8b27-6d572d0032f9", "title": "FACTREL (gonadorelin hydrochloride) injection, Zoetis Inc. — FDA-approved animal drug labeling", "publisher": "DailyMed (U.S. National Library of Medicine)", "date": "2026-06-18", "quote": "For use in animals only. Not for human use." }, "verifiedAt": "2026-08-02" } ] }, { "slug": "ibutamoren", "name": "Ibutamoren", "aliases": [ "MK-677", "MK-0677", "Ibutamoren Mesylate", "L-163,191", "Oratrope" ], "url": "https://peptides101.com/compounds/ibutamoren", "moleculeNote": "Not a peptide, despite being sold throughout the research-peptide market and routinely catalogued alongside GHRPs. Ibutamoren is an orally active non-peptide spiropiperidine — a ghrelin-receptor (GHS-R1a) agonist that acts as a growth hormone secretagogue. This distinction is not pedantry: FDA's Category 2 rationale for the surrounding peptides (ipamorelin, GHRP-2, GHRP-6, kisspeptin-10) turns on immunogenicity and peptide-related impurities. Ibutamoren's does not. Its listed risk is pharmacological, and it is cardiac. FDA lists the mesylate salt, which is the form nominated and the form sold.", "quickAnswer": "Ibutamoren (MK-677) is not approved by FDA, which states that its safety and efficacy have not been established; FDA has determined that it is excluded from the definition of a dietary supplement; and FDA has placed ibutamoren mesylate in Category 2 of its 503A bulk drug substances list — substances that raise significant safety risks — over the potential for congestive heart failure. It does have real human trial data, and that data is largely negative: in a 2008 two-year placebo-controlled trial of 65 healthy adults aged 60 to 81, researchers reported that fat-free mass increased but that the gain produced no change in strength or function, while fasting glucose rose and insulin sensitivity decreased.", "fdaStatus": { "value": "not-approved", "note": "Not an FDA-approved drug for any indication, and not in active development toward approval. That says nothing about whether it is sold — it is.", "source": { "url": "https://www.fda.gov/media/94155/download", "title": "Bulk Drug Substances Nominated for Use in Compounding Under Section 503A of the Federal Food, Drug, and Cosmetic Act", "publisher": "FDA", "date": "2026-05-14" }, "verifiedAt": "2026-07-16" }, "compoundingStatus": { "value": "category-2", "note": "Present by name, as 'Ibutamoren Mesylate', in Category 2 of the list updated 2026-05-14 — verified by fetching and text-extracting the document directly. Category 2 contains exactly six substances: Cesium Chloride, Domperidone, Germanium Sesquioxide, Ibutamoren Mesylate, Kisspeptin-10, and Quinacrine Hydrochloride for intrauterine administration. Ibutamoren is therefore one of the few compounds in this corpus whose Category 2 status is current fact rather than a stale claim about a withdrawn nomination. It is also listed under 503B (designated 2022-12-29). Category 2 is not the criminal line either: the Watkins indictment (D. Utah, 1:26-cr-00015, 2026-04-01) charges misbranding under 352(b), which is why Category 1 substances appear in the same indictment as Category 2 and unlisted ones. Sourcing and labeling are the line.", "source": { "url": "https://www.fda.gov/media/94155/download", "title": "Bulk Drug Substances Nominated for Use in Compounding Under Section 503A of the Federal Food, Drug, and Cosmetic Act", "publisher": "FDA", "date": "2026-05-14" }, "verifiedAt": "2026-07-16" }, "evidence": { "tier": "promising-but-unproven", "humanAdministrationChecked": true, "note": "Administration check run per-study, not inferred from counts. Both trials below were opened and confirmed to have ADMINISTERED ibutamoren orally to human participants — neither measures an endogenous analyte as a biomarker, so the trap that voids the apparent human evidence for MOTS-c and TB-500 does not apply. In a 2008 two-year double-blind placebo-controlled modified-crossover trial of 65 healthy adults aged 60-81 (Nass et al., Ann Intern Med, PMID 18981485), researchers administered oral MK-677 or placebo daily and reported that GH and IGF-I rose into the young-adult range and mean fat-free mass increased by 1.1 kg versus a 0.5 kg decrease on placebo. The authors also reported that the fat-free mass gain did not translate into strength or function, that fasting glucose rose and insulin sensitivity decreased, that cortisol rose, and that limb fat increased more than on placebo. Limitations, stated by the authors: 'Study power (duration and participant number) was insufficient to evaluate functional end points in healthy elderly persons.' The scope-limiting phrase is the authors' own and is kept: they stated the limitation for the population they studied, not as a general claim about the drug. In a 2011 multicenter randomized placebo-controlled Phase IIb trial of 123 elderly hip fracture patients (Adunsky et al., Arch Gerontol Geriatr, PMID 21067829), researchers administered oral MK-0677 or placebo daily and reported that IGF-1 rose by 51.4 ng/ml while most functional performance measures did not improve; the trial was terminated early for a congestive heart failure signal, and the authors concluded an unfavorable safety profile in that population. The precise statement: real, adequately-blinded human administration data exists, and it is largely NEGATIVE on the outcomes people buy this compound for. Ibutamoren reliably raises GH and IGF-1 — that pharmacodynamic effect is well established and is not in dispute. What is not established is that the hormonal change produces clinical benefit: the two trials that looked for strength and function did not find it. 'Promising but unproven' here means tested and failed, not untested. No FDA approval for any indication was ever granted; Merck's development programme did not yield one. Separately, NCT05364684 (ibutamoren in nonalcoholic fatty liver disease) was checked and is a legitimate registration — Massachusetts General Hospital, Phase 2, started 2022-08-10, COMPLETED, results posted. It is unrelated to the eight-registration Hudson Biotech cluster contaminating this vertical. Its results were not read for this record, so no outcome is claimed from it and it is not relied on for the tier.", "source": { "url": "https://pubmed.ncbi.nlm.nih.gov/18981485/", "title": "Effects of an oral ghrelin mimetic on body composition and clinical outcomes in healthy older adults: a randomized trial", "publisher": "Annals of Internal Medicine", "date": "2008-11-04", "quote": "Increased fat-free mass did not result in changes in strength or function." }, "verifiedAt": "2026-07-16" }, "fdaApproval": null, "fdaFindings": [ { "finding": "FDA placed ibutamoren mesylate in Category 2 — bulk drug substances that raise significant safety risks — for both 503A (2023-09-29) and 503B (2022-12-29) compounding, on the basis of a cardiac signal seen in a human trial.", "note": "Unlike the seven substances before PCAC on 23-24 July 2026, ibutamoren has no briefing document and is not on that agenda — its status is settled rather than pending, so there is no 'we propose not adding' language to quote and no advisory-committee outcome to await. Do not compress the category into the legal bar: these are two distinct facts, and an earlier draft of this note fused them into one causal claim ('Category 2 placement means it cannot be used in compounding'). It does not mean that. What bars lawful use is the baseline section 503A(b)(1)(A) requirement, which would bite identically on a Category 1 or an unlisted substance; Category 2 is the separate fact that FDA declines to extend its Category 1 enforcement forbearance. FDA's guidance says in terms that Category 2 substances 'may be eligible for inclusion on the 503A bulks list' — see the interim-policy finding below, which carries both mechanisms in FDA's own words. Note what FDA's rationale rests on: not an absence of data, but the presence of it. The trial FDA cites is Adunsky et al. 2011 (PMID 21067829), which is the same trial the market cites as evidence ibutamoren 'works' for recovery. It is the reason FDA calls it unsafe.", "source": { "url": "https://www.fda.gov/drugs/human-drug-compounding/certain-bulk-drug-substances-use-compounding-may-present-significant-safety-risks", "title": "Certain Bulk Drug Substances for Use in Compounding that May Present Significant Safety Risks", "publisher": "FDA", "date": "2023-09-29", "quote": "Ibutamoren mesylate poses significant safety risks due to the potential for congestive heart failure in certain patients. The agency is aware of a randomized, placebo-controlled trial assessing ibutamoren mesylate for the treatment of patients recovering from hip fracture that “was terminated early due to a potential safety signal of congestive heart failure.”" }, "verifiedAt": "2026-07-16" }, { "finding": "FDA states that ibutamoren is not an FDA-approved active ingredient and that its safety and efficacy have not been established, and that the long-term effects of ibutamoren use are unknown.", "note": "The flattest, most quotable statement of ibutamoren's approval status in FDA's own voice, and it is not in the bulks list — it is in a consumer health-fraud notification. Word-for-word identical language appears in the Agebox warning letter (MARCS-CMS 718252, 2025-12-19) — two documents, but one firm and one laboratory finding, so treat this as FDA saying it twice rather than as independent corroboration. An earlier draft of this note also cited the Musclepower Enterprise letter (MARCS-CMS 719339, 2025-12-12) for this language. That letter does not contain it: it carries the dietary-supplement exclusion determination and nothing about approval status or side effects. The citation was removed rather than softened. Read the finding against the record's own evidence note: 'not approved' and 'safety and efficacy have not been established' are true, and are NOT the same claim as 'untested'. Merck ran real placebo-controlled human trials. Nothing came of them. The middle of the ellipsis is FDA's adverse-effect enumeration, quoted in full in the finding below.", "source": { "url": "https://www.fda.gov/drugs/medication-health-fraud-notifications/agebox-ikids-growth-day-formula-may-be-harmful-due-hidden-ingredient", "title": "Agebox iKids Growth Day Formula may be harmful due to hidden ingredient", "publisher": "FDA", "date": "2025-09-23", "quote": "Ibutamoren (also known as MK-677) is an active ingredient not approved by FDA, and therefore its safety and efficacy have not been established. Ibutamoren is a growth hormone secretagogue that stimulates the release of growth hormone. ... Long-term effects of ibutamoren use are unknown and may pose additional health risks." }, "verifiedAt": "2026-07-16" }, { "finding": "FDA has determined that ibutamoren is excluded from the definition of a dietary supplement, because it was authorized for investigation as a new drug and substantial clinical investigations were instituted and made public before it was ever marketed as a supplement or food.", "note": "The most useful finding on this record for anyone reading a label, and the one with the sharpest irony in it. The drug-exclusion clause bites BECAUSE Merck did the clinical work: the very existence of the public IND is what forecloses the supplement route forever. A compound with no trials behind it would not be excluded on this ground. So the trials the market cites as proof ibutamoren works are, verbatim, FDA's stated reason it cannot lawfully be sold as a supplement. There is no combination of formulation, labeling or disclaimer that cures this — the exclusion attaches to the substance, not to the marketing.", "source": { "url": "https://www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/warning-letters/agebox-inc-718252-12192025", "title": "Warning Letter — Agebox Inc., MARCS-CMS 718252", "publisher": "FDA", "date": "2025-12-19", "quote": "Based on available evidence, ibutamoren has been authorized for investigation as a new drug, substantial clinical investigations of ibutamoren as a new drug have been instituted, and the existence of such investigations has been made public, and ibutamoren was not marketed as a dietary supplement or as a conventional food prior to such authorization. Therefore, FDA has determined that ibutamoren is excluded from the definition of a dietary supplement under section 201(ff)(3)(B)(ii) of the FD&C Act, 21 U.S.C. 321(ff)(3)(B)(ii)." }, "verifiedAt": "2026-07-16" }, { "finding": "In a warning letter, FDA enumerated the adverse effects it associates with ibutamoren: increased appetite, water retention, fatigue, muscle pain, potential alterations in glucose metabolism and insulin sensitivity, and increased potential for congestive heart failure in certain individuals.", "note": "Notable for being broader than the Category 2 entry, which cites only the congestive heart failure signal. Here FDA independently names the glucose and insulin-sensitivity effects, the edema and the muscle pain — which is the full published adverse-event profile of the 2008 Nass trial (PMID 18981485), reassembled in FDA's voice without the trial's favorable body-composition result beside it. The context matters and is not incidental: FDA's laboratory analysis had found ibutamoren mesylate UNDECLARED in products sold for children aged five and older, so this list was written about children who were given the drug without anyone knowing.", "source": { "url": "https://www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/warning-letters/agebox-inc-718252-12192025", "title": "Warning Letter — Agebox Inc., MARCS-CMS 718252", "publisher": "FDA", "date": "2025-12-19", "quote": "Use of ibutamoren may cause serious side effects including increased appetite, water retention, fatigue, muscle pain, potential alterations in glucose metabolism and insulin sensitivity, and even may increase the potential for congestive heart failure in certain individuals." }, "verifiedAt": "2026-07-16" }, { "finding": "FDA's interim policy defines Category 2 as substances that were nominated with enough information to evaluate and that may still be eligible for the 503A bulks list, but for which FDA has identified significant safety risks in compounding — and for which it therefore does not intend to adopt the enforcement policy it applies to Category 1.", "note": "The finding that stops this record from saying something FDA did not say. Two mechanisms live in this guidance and they are constantly fused into one. Mechanism one, the statutory bar, which is what actually makes ibutamoren unusable: 'a bulk drug substance that is not the subject of an applicable USP or NF monograph or is not a component of an FDA-approved drug product cannot be used in compounding unless it appears on a list promulgated as a regulation ... A drug product compounded from a bulk drug substance that does not meet any of these three conditions is not eligible for the exemptions in section 503A and may violate the FD&C Act.' That bar does not care about categories. Mechanism two, the enforcement forbearance, which is what the category actually governs: FDA states it 'does not intend to take action against a State-licensed pharmacy, Federal facility, or licensed physician compounding a drug product using a bulk drug substance' meeting none of the three statutory conditions, but only 'if all of the following circumstances are present: (1) The bulk drug substance appears in 503A Category 1 on FDA's website'. Ibutamoren mesylate is in Category 2, so that forbearance is not extended to it. Read those together and the honest sentence is narrow: Category 2 does not make ibutamoren illegal to compound — the statutory bar already did that — it means FDA has not said it will refrain from acting against a compounder who uses it anyway. Note also what Category 2 does NOT mean, because the inverse error is just as common: FDA's own definition says these substances 'may be eligible for inclusion on the 503A bulks list'. Category 2 is a pending safety determination, not a permanent ban.", "source": { "url": "https://www.fda.gov/media/174456/download", "title": "Interim Policy on Compounding Using Bulk Drug Substances Under Section 503A of the Federal Food, Drug, and Cosmetic Act — Guidance for Industry", "publisher": "FDA", "date": "2025-01-07", "quote": "503A Category 2 – Substances Nominated for the Bulks List That Raise Significant Safety Risks: These substances were nominated with sufficient supporting information to permit FDA to evaluate them, and they may be eligible for inclusion on the 503A bulks list. However, FDA has identified significant safety risks relating to the use of these substances in compounding pending further evaluation and, therefore, does not intend to adopt the policy described for the substances in Category 1." }, "verifiedAt": "2026-07-16" }, { "finding": "FDA lists ibutamoren mesylate in the table of substances currently in Category 2 — not in the separate list of substances previously in Category 2 whose nominations were withdrawn by the nominators.", "note": "A structural finding, and the one that separates ibutamoren from most of this corpus. FDA's page carries two distinct lists, and which list a substance is on is the whole question. BPC-157, MOTS-c, TB-500, epitalon, KPV, semax and the rest sit in the withdrawn list — their nominators walked away, and the market misreads that departure as FDA relenting. Ibutamoren mesylate sits in the live table, by name, with its designation dates in the adjacent column, verified against the list updated 2026-05-14. Nothing here moved sideways. Neither list is a route to lawful supply, but only one of them is a standing FDA safety determination, and ibutamoren is on it.", "source": { "url": "https://www.fda.gov/drugs/human-drug-compounding/certain-bulk-drug-substances-use-compounding-may-present-significant-safety-risks", "title": "Certain Bulk Drug Substances for Use in Compounding that May Present Significant Safety Risks", "publisher": "FDA", "date": "2023-09-29", "quote": "Bulk drug substances that may present significant safety risks have been placed in category 2 under the interim policies. ... Bulk drug substances nominated but withdrawn ... This list of bulk drug substances previously in category 2 of the interim policies were withdrawn by the nominators." }, "verifiedAt": "2026-07-16" } ], "safetySignals": [ { "signal": "A randomized, double-blind, placebo-controlled Phase IIb trial of 123 elderly hip fracture patients was terminated early for a congestive heart failure signal. The authors concluded that MK-0677 has an unfavorable safety profile in this population, and that the rise in IGF-1 was not paralleled by improvement in most functional performance measures.", "note": "This is the trial FDA relies on for the Category 2 designation. An earlier draft of this entry reported the congestive-heart-failure events as a 4-of-62 versus 1-of-61 split. Those per-arm counts are not in the abstract this entry cites — the abstract says only 'a limited number of patients' — and the draft attributed them to unspecified 'secondary reporting' while citing PubMed. A number sourced to a document that does not contain it is the defect this site exists to correct, so the counts are removed rather than re-attributed to a source we have not read. What the abstract does carry, verbatim, is the termination, the unfavorable safety conclusion, and the arm sizes (n = 62 MK-0677, n = 61 placebo). The population was elderly hip fracture patients, who carry elevated baseline cardiac risk — this signal should not be silently generalized to healthy younger users, nor dismissed as irrelevant to them.", "source": { "url": "https://pubmed.ncbi.nlm.nih.gov/21067829/", "title": "MK-0677 (ibutamoren mesylate) for the treatment of patients recovering from hip fracture: a multicenter, randomized, placebo-controlled phase IIb study", "publisher": "Archives of Gerontology and Geriatrics", "date": "2011-09-01", "quote": "Trial was terminated early due to a safety signal of congestive heart failure in a limited number of patients." }, "verifiedAt": "2026-07-16" }, { "signal": "In the 2008 two-year trial in healthy older adults, researchers reported that fasting blood glucose rose an average of 0.3 mmol/L (5 mg/dL) and insulin sensitivity decreased in the MK-677 group, and that cortisol rose by 47 nmol/L.", "note": "Reported in the trial the market cites most often for the fat-free mass result. The same paper that supplies the favorable body-composition number also supplies the glucose, insulin-sensitivity and cortisol findings, and reports that the fat-free mass gain did not produce strength or function gains.", "source": { "url": "https://pubmed.ncbi.nlm.nih.gov/18981485/", "title": "Effects of an oral ghrelin mimetic on body composition and clinical outcomes in healthy older adults: a randomized trial", "publisher": "Annals of Internal Medicine", "date": "2008-11-04", "quote": "Fasting blood glucose level increased an average of 0.3 mmol/L (5 mg/dL) in the MK-677 group (P = 0.015), and insulin sensitivity decreased." }, "verifiedAt": "2026-07-16" }, { "signal": "The most frequent side effects in the 2008 trial were an increase in appetite that subsided within a few months, and transient mild lower-extremity edema and muscle pain.", "note": "Edema is worth reading alongside the congestive heart failure signal from the hip fracture trial rather than in isolation, given fluid retention is a recognized consequence of raising GH/IGF-1. The two reports are consistent with one mechanism; that connection is ours and is not asserted by either paper or by FDA.", "source": { "url": "https://pubmed.ncbi.nlm.nih.gov/18981485/", "title": "Effects of an oral ghrelin mimetic on body composition and clinical outcomes in healthy older adults: a randomized trial", "publisher": "Annals of Internal Medicine", "date": "2008-11-04", "quote": "The most frequent side effects were an increase in appetite that subsided in a few months and transient, mild lower-extremity edema and muscle pain." }, "verifiedAt": "2026-07-16" } ], "faqs": [ { "question": "Is MK-677 legal in 2026?", "answer": "No, MK-677 (ibutamoren) has no lawful route to consumer sale in the United States. FDA has determined that ibutamoren is excluded from the definition of a dietary supplement under section 201(ff)(3)(B)(ii) of the Federal Food, Drug, and Cosmetic Act, so it cannot be sold as a supplement; it is not an FDA-approved drug; and FDA has told a firm selling an ibutamoren-containing product that its products are \"unapproved new drugs introduced or delivered for introduction into interstate commerce in violation of sections 505(a) and 301(d) of the Federal Food, Drug, and Cosmetic Act.\" Note who that violation runs to: FDA addressed it to the seller, not to buyers.", "source": { "url": "https://www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/warning-letters/agebox-inc-718252-12192025", "title": "Warning Letter — Agebox Inc., MARCS-CMS 718252", "publisher": "FDA", "date": "2025-12-19", "quote": "As described below, these products are unapproved new drugs introduced or delivered for introduction into interstate commerce in violation of sections 505(a) and 301(d) of the Federal Food, Drug, and Cosmetic Act (FD&C Act), 21 U.S.C. 355(a) and 331(d)." }, "verifiedAt": "2026-07-16" }, { "question": "Did FDA approve ibutamoren (MK-677)?", "answer": "No. FDA has never approved ibutamoren (MK-677) for any indication or population. FDA states directly that ibutamoren \"is an active ingredient not approved by FDA, and therefore its safety and efficacy have not been established\" and that \"long-term effects of ibutamoren use are unknown and may pose additional health risks.\" Ibutamoren was developed as an investigational drug and taken into human trials, but that development programme never produced an approval.", "source": { "url": "https://www.fda.gov/drugs/medication-health-fraud-notifications/agebox-ikids-growth-day-formula-may-be-harmful-due-hidden-ingredient", "title": "Agebox iKids Growth Day Formula may be harmful due to hidden ingredient", "publisher": "FDA", "date": "2025-09-23" }, "verifiedAt": "2026-07-16" }, { "question": "Is there any human evidence that MK-677 builds muscle?", "answer": "There is real human trial evidence for MK-677 (ibutamoren), and it does not support a strength or function benefit. In a 2008 two-year randomized, double-blind, placebo-controlled trial of 65 healthy adults aged 60 to 81 (Nass et al., Annals of Internal Medicine, PMID 18981485), researchers administered oral MK-677 or placebo and reported that growth hormone and IGF-I rose into the young-adult range and mean fat-free mass increased by 1.1 kg versus a 0.5 kg decrease on placebo — but concluded that \"increased fat-free mass did not result in changes in strength or function.\" The same trial reported that fasting glucose rose and insulin sensitivity decreased. MK-677 raises GH and IGF-1 reliably; that hormonal effect is well established. What the trials did not find is that the hormonal change delivers the outcome.", "source": { "url": "https://pubmed.ncbi.nlm.nih.gov/18981485/", "title": "Effects of an oral ghrelin mimetic on body composition and clinical outcomes in healthy older adults: a randomized trial", "publisher": "Annals of Internal Medicine", "date": "2008-11-04", "quote": "Increased fat-free mass did not result in changes in strength or function." }, "verifiedAt": "2026-07-16" }, { "question": "Can I get MK-677 from a compounding pharmacy?", "answer": "No. FDA placed ibutamoren mesylate (MK-677) in Category 2 of both the 503A list (September 29, 2023) and the 503B list (December 29, 2022) — bulk drug substances that raise significant safety risks — and it remains there on the list updated May 14, 2026. FDA's stated reason is that \"ibutamoren mesylate poses significant safety risks due to the potential for congestive heart failure in certain patients,\" and that the agency \"is aware of a randomized, placebo-controlled trial assessing ibutamoren mesylate for the treatment of patients recovering from hip fracture that 'was terminated early due to a potential safety signal of congestive heart failure.'\" Ibutamoren is one of only six substances in 503A Category 2, alongside cesium chloride, domperidone, germanium sesquioxide, kisspeptin-10, and quinacrine hydrochloride for intrauterine administration.", "source": { "url": "https://www.fda.gov/drugs/human-drug-compounding/certain-bulk-drug-substances-use-compounding-may-present-significant-safety-risks", "title": "Certain Bulk Drug Substances for Use in Compounding that May Present Significant Safety Risks", "publisher": "FDA", "date": "2023-09-29", "quote": "Ibutamoren mesylate poses significant safety risks due to the potential for congestive heart failure in certain patients. The agency is aware of a randomized, placebo-controlled trial assessing ibutamoren mesylate for the treatment of patients recovering from hip fracture that “was terminated early due to a potential safety signal of congestive heart failure.”" }, "verifiedAt": "2026-07-16" }, { "question": "What does Category 2 actually mean — is it a ban?", "answer": "No, Category 2 is not a ban, and it is not what makes MK-677 unavailable. Two separate things are at work in FDA's interim policy guidance. First, the statutory bar: FDA states that \"a bulk drug substance that is not the subject of an applicable USP or NF monograph or is not a component of an FDA-approved drug product cannot be used in compounding unless it appears on a list promulgated as a regulation,\" and that a drug compounded from a substance meeting none of those three conditions \"is not eligible for the exemptions in section 503A and may violate the FD&C Act.\" That bar applies regardless of category. Second, the enforcement policy: FDA says it does not intend to take action against a state-licensed pharmacy, federal facility, or licensed physician compounding with a nominated substance, but only \"if all of the following circumstances are present: (1) The bulk drug substance appears in 503A Category 1 on FDA's website.\" Ibutamoren mesylate is in Category 2, so that forbearance does not extend to it. FDA defines Category 2 substances as ones that \"may be eligible for inclusion on the 503A bulks list\" but for which it \"has identified significant safety risks relating to the use of these substances in compounding pending further evaluation.\" So Category 2 means FDA has not promised to refrain from acting against a compounder who uses it — not that the question is permanently closed.", "source": { "url": "https://www.fda.gov/media/174456/download", "title": "Interim Policy on Compounding Using Bulk Drug Substances Under Section 503A of the Federal Food, Drug, and Cosmetic Act — Guidance for Industry", "publisher": "FDA", "date": "2025-01-07", "quote": "However, FDA has identified significant safety risks relating to the use of these substances in compounding pending further evaluation and, therefore, does not intend to adopt the policy described for the substances in Category 1. ... However, at this time, until a substance has been evaluated and is identified in a final rule as being included or not included on the 503A bulks list, FDA does not intend to take action against a State-licensed pharmacy, Federal facility, or licensed physician compounding a drug product using a bulk drug substance that is not a component of an FDA-approved drug product, the subject of an applicable USP or NF monograph, or on the 503A bulks list codified at 21 CFR 216.23(a), if all of the following circumstances are present: (1) The bulk drug substance appears in 503A Category 1 on FDA's website ..." }, "verifiedAt": "2026-07-16" }, { "question": "Is MK-677 banned in sport?", "answer": "Yes. MK-677 is named on the World Anti-Doping Agency's 2026 Prohibited List, which came into effect on 1 January 2026. It appears at S2.2.4 under growth hormone releasing factors, in the entry for \"growth hormone secretagogues (GHS) and their mimetics [e.g. anamorelin, capromorelin, ibutamoren (MK-677), ipamorelin, lenomorelin (ghrelin), macimorelin and tabimorelin].\" Class S2 is prohibited at all times — both in-competition and out-of-competition — and WADA states that all prohibited substances in the S2 class are non-Specified Substances.", "source": { "url": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "title": "World Anti-Doping Code International Standard: Prohibited List 2026", "publisher": "World Anti-Doping Agency", "date": "2026-01-01", "quote": "growth hormone secretagogues (GHS) and their mimetics [e.g. anamorelin, capromorelin, ibutamoren (MK-677), ipamorelin, lenomorelin (ghrelin), macimorelin and tabimorelin]" }, "verifiedAt": "2026-07-16" }, { "question": "Has ibutamoren been found in products that don't list it on the label?", "answer": "Yes. FDA laboratory analysis confirmed that Agebox iKids Growth Day Formula — a product promoted and sold to stimulate growth in children ages five and older — contained ibutamoren that was not listed on the product label. FDA advised consumers not to purchase or use the product in a health fraud notification dated September 23, 2025, and issued a warning letter to Agebox Inc. on December 19, 2025 stating that the failure to disclose ibutamoren mesylate rendered the products misbranded under section 502(a) of the Federal Food, Drug, and Cosmetic Act. FDA also states that it is unable to test and identify all products marketed as dietary supplements that have potentially harmful hidden ingredients.", "source": { "url": "https://www.fda.gov/drugs/medication-health-fraud-notifications/agebox-ikids-growth-day-formula-may-be-harmful-due-hidden-ingredient", "title": "Agebox iKids Growth Day Formula may be harmful due to hidden ingredient", "publisher": "FDA", "date": "2025-09-23", "quote": "FDA laboratory analysis confirmed that Agebox iKids Growth Day Formula contains ibutamoren not listed on the product label." }, "verifiedAt": "2026-07-16" } ] }, { "slug": "icatibant", "name": "Icatibant", "aliases": [ "Firazyr", "icatibant acetate", "HOE 140", "JE049" ], "url": "https://peptides101.com/compounds/icatibant", "moleculeNote": "A synthetic decapeptide, described in the FDA-approved labeling as containing five non-proteinogenic amino acids. Its pharmacological class per the label is bradykinin B2 receptor ANTAGONIST — it blocks a receptor rather than stimulating one, which is the opposite of the growth-factor and secretagogue peptides most of this site covers. The approved products contain the ACETATE SALT: FDA's product records list the active ingredient as icatibant acetate, with strength expressed as icatibant free-base equivalent. Unlike the semaglutide case, the salt is what is approved, not a substitute for it.", "quickAnswer": "Icatibant is an FDA-approved drug: FDA approved Firazyr (icatibant) injection under NDA 022150 on 25 August 2011, and the approved labeling indicates it 'for the treatment of acute attacks of hereditary angioedema (HAE) in adults 18 years of age and older' — acute attacks rather than prophylaxis, and adults only, with safety and effectiveness in patients below 18 years not established. Approval came on the second cycle: FDA took a Not Approval action on the original application in April 2008 because substantial evidence of efficacy was not demonstrated in the two pivotal studies, and the placebo-controlled trial of that pair, FAST-1, did not meet its prespecified primary endpoint; a third trial, FAST-3, showed icatibant statistically superior to placebo and carried the approval. That approval does not reach angioedema induced by ACE inhibitors — the FIRAZYR label states that clinical trials to date have excluded subjects taking ACE inhibitors, and in a later Phase 3 randomised placebo-controlled trial of 121 subjects the investigators reported no difference between icatibant and placebo in time to meeting discharge criteria. Six generic icatibant injection products are also approved, and icatibant appears in none of the three categories of FDA's 503A bulk drug substances list.", "fdaStatus": { "value": "approved", "note": "FDA-approved and marketed. Approval is always for a specific indication and population, and here it is narrow — see the approval record below. STILL CURRENT, checked rather than assumed: Drugs@FDA (openFDA `drug/drugsfda`, dataset last updated 2026-07-31) returns seven applications whose active ingredient is icatibant acetate — NDA 022150 (FIRAZYR, Takeda Pharmaceuticals U.S.A.) plus six ANDAs — and every one of the seven carries marketing status 'Prescription' rather than 'Discontinued'. Sponsorship moved over the product's life: the NDA was filed by Jerini, approved to Shire Orphan Therapies in 2011, and is held by Takeda today. Same application number throughout.", "source": { "url": "https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2011/022150s000ltr.pdf", "title": "NDA 022150 — NDA Approval Letter, Firazyr (icatibant acetate) Injection", "publisher": "FDA", "date": "2011-08-25", "quote": "This new drug application provides for the use of Firazyr (icatibant) Injection for the treatment of acute attacks of hereditary angioedema in adults 18 years of age and older. We have completed our review of this application, as amended. It is approved, effective on the date of this letter, for use as recommended in the enclosed agreed-upon labeling text." }, "verifiedAt": "2026-08-02" }, "compoundingStatus": null, "evidence": { "tier": "proven-in-humans", "humanAdministrationChecked": true, "note": "Administration check RUN, not assumed, and the trials are named rather than counted. FDA's Summary Review identifies three pivotal Phase 3 studies by internal number — 2103 (FAST-1), 2102 (FAST-2) and 054 (FAST-3) — and each was matched to its registration by PROTOCOL NUMBER rather than by name, because the label names no registrations: NCT00097695 carries org study ID 'JE049 #2103' (FAST-1, 84 enrolled ACTUAL, icatibant versus placebo), NCT00500656 carries 'JE049 #2102' (FAST-2, 85 ACTUAL, icatibant versus oral tranexamic acid), and NCT00912093 carries 'HGT-FIR-054' and names FAST-3 in its own brief title (98 ACTUAL, icatibant versus placebo). All three were opened on 2026-08-02: lead sponsor Shire, Phase 3, status COMPLETED, hasResults true, intervention type DRUG. Icatibant was ADMINISTERED subcutaneously to patients during acute attacks; it was not measured as an endogenous biomarker, which is the trap that reduces MOTS-c and TB-500 from an apparent five human RCTs to an actual zero. THE TIER IS NOT UNANIMOUS ACROSS THOSE TRIALS, and the record says so. FAST-1, the first placebo-controlled trial, MISSED its prespecified primary endpoint (p = 0.142 versus placebo, per FDA's own table), and FDA refused the original application in April 2008 on that basis. Approval rests on FAST-3, a second placebo-controlled trial that met a REDEFINED primary endpoint, plus FAST-3's key secondary endpoint, which was the endpoint FAST-1 had failed. Both of those are recorded below with their own sources. SCOPE — the tier attaches to the treatment of acute attacks of hereditary angioedema in adults, and to nothing else. It does not extend to routine prophylaxis, to patients under 18, or to angioedema induced by ACE inhibitors, where the Phase 3 trial that tested this exact molecule reported no difference from placebo.", "source": { "url": "https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022150Orig1s000SumR.pdf", "title": "Summary Review of Regulatory Action — NDA 22-150, Firazyr (icatibant)", "publisher": "FDA", "date": "2011-08-24", "quote": "The additional study, FAST-3, which used a placebo control, showed that icatibant was statistically superior to placebo on the prespecified efficacy endpoint of 3-symptom composite VAS (Table 3)." }, "verifiedAt": "2026-08-02" }, "fdaApproval": { "applicationNumber": "NDA 022150", "brandName": "Firazyr", "approvedIndication": "FIRAZYR® (icatibant) is indicated for the treatment of acute attacks of hereditary angioedema (HAE) in adults 18 years of age and older.", "discontinued": false, "source": { "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/022150s016lbl.pdf", "title": "FIRAZYR (icatibant) Injection, for subcutaneous use — Full Prescribing Information", "publisher": "FDA", "date": "2024-01-19", "quote": "FIRAZYR® (icatibant) is indicated for the treatment of acute attacks of hereditary angioedema (HAE) in adults 18 years of age and older." }, "verifiedAt": "2026-08-02" }, "fdaFindings": [ { "finding": "FDA took a Not Approval action on the original icatibant application in April 2008, because substantial evidence of efficacy was not demonstrated in the two pivotal studies submitted with it. Approval followed only after a third controlled study.", "note": "Independently corroborated inside the approval letter, which refers to FDA's 'April 23, 2008, action letter' and records that the February 25, 2011 submission 'constituted a complete response' to it. Two FDA documents, same fact. This matters beyond history. An approved drug is routinely described as though its evidence arrived clean; here FDA is on record that it did not, and the reason is methodological rather than pharmacological — a failed placebo comparison and an active comparator FDA did not accept.", "source": { "url": "https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022150Orig1s000SumR.pdf", "title": "Summary Review of Regulatory Action — NDA 22-150, Firazyr (icatibant)", "publisher": "FDA", "date": "2011-08-24", "quote": "The original NDA was submitted in October 2007, and a Not Approval action was taken in April 2008, because substantial evidence of efficacy was not demonstrated in two pivotal studies. The original NDA included one placebo-controlled study that did not show efficacy, and another tranexamic acid (TA) active-controlled study that showed efficacy." }, "verifiedAt": "2026-08-02" }, { "finding": "On the prespecified primary endpoint of the two original pivotal trials, FDA reported that icatibant was statistically superior to tranexamic acid in FAST-2 but NOT to placebo in FAST-1. FDA's table records p = 0.142 for FAST-1 against placebo for all attacks, with cutaneous and abdominal attacks at p = 0.221 and p = 0.159.", "note": "Recorded because a positive result on a redefined endpoint is not the same thing as a positive result, and the difference is invisible from the label. FDA is explicit that FAST-3 used a DIFFERENT definition of symptom relief from FAST-1 and FAST-2, that a post-hoc reanalysis of FAST-1 under FAST-3's endpoint did reach significance (p = 0.014), and that these are 'post hoc analyses'. FDA also flagged that blinding may have been imperfect — icatibant produces injection site reactions in almost all patients — writing that 'there is no assurance that the blinding succeeded' and that the confounding influence 'cannot be completely ruled out'. FDA's own resolution of that concern was FAST-3: 'the additional FAST-3 study showing efficacy in a placebo-controlled study is reassuring of efficacy.'", "source": { "url": "https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022150Orig1s000SumR.pdf", "title": "Summary Review of Regulatory Action — NDA 22-150, Firazyr (icatibant)", "publisher": "FDA", "date": "2011-08-24", "quote": "Based on the prespecified primary efficacy endpoint of median time to onset of symptom relief as measured by single-symptom VAS, icatibant was statistically superior to TA in FAST-2 study, but not to placebo in FAST-1 study (Table 2). Results of FAST-1 showed numerical trend for icatibant over placebo, but the difference was not statistically significant." }, "verifiedAt": "2026-08-02" }, { "finding": "FDA found that tranexamic acid was not a valid active control for acute attacks of hereditary angioedema, and that efficacy shown against it in FAST-2 was not adequate for approval because tranexamic acid is not approved for that use.", "note": "The general lesson is bigger than this drug: beating a comparator establishes nothing unless the comparator works. FDA searched the literature and found three studies using tranexamic acid for acute attacks, in 5, 7 and 27 patients respectively, and noted the package insert and literature 'seem to support its use for chronic long-term therapy, but not for acute attacks'. FDA went further and observed that the cross-trial comparison ran the wrong way for the sponsor's expert opinion — tranexamic acid 'performed appreciably worse in one study compared to placebo in the other study'.", "source": { "url": "https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022150Orig1s000SumR.pdf", "title": "Summary Review of Regulatory Action — NDA 22-150, Firazyr (icatibant)", "publisher": "FDA", "date": "2011-08-24", "quote": "The existing data do not support use of TA as a valid active control. With no data supporting it use, an important question is whether TA could perform worse than placebo." }, "verifiedAt": "2026-08-02" }, { "finding": "The FDA-approved labeling states that safety and effectiveness of FIRAZYR in pediatric patients below the age of 18 years have not been established.", "note": "Read alongside the label's juvenile animal data, which is why the gap is not merely administrative: the label reports that subcutaneous daily administration to young rats during the juvenile period of development delayed sexual maturation of male reproductive tissues, and that impaired fertility and reproductive performance were also observed in male rats at the end of the postnatal treatment period. The label attributes these to antagonism of the bradykinin B2 receptor and subsequent effects on gonadotropins. Note also what the approval letter records: because the product carried orphan drug designation for this indication, the sponsor was EXEMPT from the pediatric assessment that the Pediatric Research Equity Act would otherwise require.", "source": { "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/022150s016lbl.pdf", "title": "FIRAZYR (icatibant) Injection, for subcutaneous use — Full Prescribing Information", "publisher": "FDA", "date": "2024-01-19", "quote": "Safety and effectiveness in pediatric patients below the age of 18 years have not been established." }, "verifiedAt": "2026-08-02" }, { "finding": "The FDA-approved labeling states that FIRAZYR, as a bradykinin B2 receptor antagonist, has the potential for a pharmacodynamic interaction with ACE inhibitors and may attenuate their antihypertensive effect, and that clinical trials to date have excluded subjects taking ACE inhibitors.", "note": "The most under-read sentence on this label. The single largest off-label use of icatibant is angioedema in patients ON an ACE inhibitor — and the label states that the trials behind the approval excluded exactly those patients. FDA's Summary Review explains the exclusion as clinical practice rather than a safety finding: ACE inhibitors are generally avoided in hereditary angioedema patients because of their own potential to cause angioedema. Either way, the approved evidence base does not contain these patients, and the trial that was later run in them is recorded below.", "source": { "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/022150s016lbl.pdf", "title": "FIRAZYR (icatibant) Injection, for subcutaneous use — Full Prescribing Information", "publisher": "FDA", "date": "2024-01-19", "quote": "FIRAZYR is a bradykinin B2 receptor antagonist and thereby has the potential to have a pharmacodynamic interaction with ACE inhibitors where FIRAZYR may attenuate the antihypertensive effect of ACE inhibitors. Clinical trials to date have excluded subjects taking ACE inhibitors." }, "verifiedAt": "2026-08-02" }, { "finding": "Icatibant appears in none of Categories 1, 2 or 3 of FDA's 503A bulk drug substances list updated 2026-05-14.", "note": "Recorded to close a misreading, not to assert a status — which is why this record carries no compoundingStatus at all. Verified by fetching the document with a browser user-agent and text-extracting it locally on 2026-08-02: zero hits for 'icatibant' across all seven pages. That absence is not BPC-157's absence. BPC-157 was nominated and left Category 2 when its nominators withdrew; icatibant was never in this system, because the 503A bulks list is the route for substances that are neither the subject of a USP monograph nor a component of an approved drug product, and icatibant is a component of seven approved drug products. Categorical silence here is neither permission nor a safety finding.", "source": { "url": "https://www.fda.gov/media/94155/download", "title": "Bulk Drug Substances Nominated for Use in Compounding Under Section 503A of the Federal Food, Drug, and Cosmetic Act", "publisher": "FDA", "date": "2026-05-14" }, "verifiedAt": "2026-08-02" }, { "finding": "Six abbreviated new drug applications for icatibant acetate injection are approved and in prescription marketing status, the first to Teva on 2019-07-15, alongside the originator NDA 022150. All six products carry therapeutic equivalence code AP.", "note": "Queried directly against FDA's own API on 2026-08-02; dataset last updated 2026-07-31. The six, by original approval date: Teva ANDA 210118 (2019-07-15), Jiangsu Hansoh ANDA 211021 (2020-03-09), Fresenius Kabi ANDA 208317 (2020-06-18), Cipla ANDA 212446 (2020-07-13), Eugia ANDA 213521 (2023-08-14), Alembic ANDA 213773 (2024-06-14). Two things follow that are easy to get wrong. A generic is approved as therapeutically equivalent to the reference product FOR THE REFERENCE PRODUCT'S INDICATION — the arrival of generics widened availability, not the approved use. And a generic is an approved drug product, not a compounded one: none of this is evidence about compounded or research-labelled material.", "source": { "url": "https://api.fda.gov/drug/drugsfda.json?search=openfda.generic_name:\"icatibant\"&limit=10", "title": "Drugs@FDA records for icatibant (openFDA drug/drugsfda API)", "publisher": "FDA", "date": "2026-07-31" }, "verifiedAt": "2026-08-02" } ], "safetySignals": [ { "signal": "The most commonly reported adverse reactions in the clinical trials were injection site reactions, which occurred in almost all patients (97%). Other common adverse reactions occurring in greater than 1% of patients included pyrexia, transaminase increase, dizziness, and rash.", "note": "97% versus 33% on placebo in the two placebo-controlled trials, per the label's Table 1. FDA characterised these reactions in its Summary Review as self-limiting, resolving within a few hours, and 'irritant in nature rather than mediated by specific immune response'. The same near-universal reaction is why FDA doubted the blinding held in the pivotal trials — a signal that is simultaneously a tolerability finding and a methodological one.", "source": { "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/022150s016lbl.pdf", "title": "FIRAZYR (icatibant) Injection, for subcutaneous use — Full Prescribing Information", "publisher": "FDA", "date": "2024-01-19", "quote": "The most commonly reported adverse reactions were injection site reactions, which occurred in almost all patients (97%) in clinical trials. Other common adverse reactions occurring in greater than 1% of patients included pyrexia, transaminase increase, dizziness, and rash." }, "verifiedAt": "2026-08-02" }, { "signal": "The FDA-approved labeling states that FIRAZYR should be used during acute coronary ischemia, unstable angina pectoris, or in the weeks following a stroke only if the benefit exceeds the theoretical risk to the patient, and that there is limited human experience in acute ischemia.", "note": "A mechanism-derived caution, and the most clinically loaded thing on this label. The label reports that icatibant decreased coronary blood flow in the isolated guinea pig heart, aggravated the duration of post-ischemic reperfusion arrhythmias in the isolated rat heart, and that intracoronary infusion in an anesthetized myocardial infarction dog model increased mortality rate two-fold over saline ischemia. Note that FIRAZYR has NO contraindications — section 4 of the label reads 'None' — so this warning is carried entirely by a nonclinical section that a reader skimming for contraindications will never reach.", "source": { "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/022150s016lbl.pdf", "title": "FIRAZYR (icatibant) Injection, for subcutaneous use — Full Prescribing Information", "publisher": "FDA", "date": "2024-01-19", "quote": "The B2 receptor has been implicated in the cardioprotective effects of bradykinin and antagonism of this receptor could potentially have negative cardiovascular effects during reperfusion after acute ischemia. … There is limited human experience in acute ischemia. FIRAZYR should be used during acute coronary ischemia, unstable angina pectoris, or in the weeks following a stroke only if the benefit exceeds the theoretical risk to the patient." }, "verifiedAt": "2026-08-02" }, { "signal": "In animals, daily subcutaneous administration of icatibant to rats and dogs caused ovarian, uterine, and testicular atrophy or degeneration and adverse effects on the mammary and prostate glands. The labeling records that these toxicities did NOT occur in dogs treated twice a week for 9 months.", "note": "The contrast in the label's own words is the finding, and it is the reason this is a signal rather than a scare. FDA's Summary Review states the reproductive toxicities 'would not preclude approval given the severity of HAE disease and the fact that animals were dosed daily, whereas humans will receive icatibant intermittently'. That reasoning is entirely contingent on intermittent use for acute attacks — which is what the approved indication describes and what any prophylactic or continuous off-label pattern would not. The specific exposure figures in the label are elided here under this site's no-dosing policy; no finding above depends on them. Separately, the label reports two-year carcinogenicity studies in mice and rats with no evidence of tumorigenicity, and negative genotoxicity across the Ames test, a chromosome aberration assay and the mouse micronucleus test.", "source": { "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/022150s016lbl.pdf", "title": "FIRAZYR (icatibant) Injection, for subcutaneous use — Full Prescribing Information", "publisher": "FDA", "date": "2024-01-19", "quote": "Daily subcutaneous administration of icatibant to rats and dogs caused ovarian, uterine, and testicular atrophy/degeneration and adverse effects on the mammary and prostate glands. … In contrast to the effects of daily icatibant administration, toxicity to the ovary, uterus, testis, mammary gland, and prostate did not occur in dogs treated twice a week for 9 months." }, "verifiedAt": "2026-08-02" }, { "signal": "In animal reproduction studies, icatibant administered subcutaneously during the period of organogenesis did not cause structural abnormalities in rats or rabbits; however, premature birth and abortion were observed in rabbits, decreased embryofetal survival was observed in rabbits, and in a rat pre- and post-natal development study delayed parturition was observed which resulted in deaths of dams, with fetal death and early pup deaths also observed. Available human data from published literature and the pharmacovigilance database have not identified a drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes.", "note": "Both halves belong on the page. The human signal is reassuring and the animal signal is not, and a record that reported either alone would be misleading. The exposure multiples the label attaches to each animal finding are elided under this site's no-dosing policy. The label does not state a conclusion about human pregnancy risk beyond the sentence quoted, and neither does this record.", "source": { "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/022150s016lbl.pdf", "title": "FIRAZYR (icatibant) Injection, for subcutaneous use — Full Prescribing Information", "publisher": "FDA", "date": "2024-01-19", "quote": "Available data from published literature and the pharmacovigilance database with Firazyr (icatibant) use in pregnant women have not identified a drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. In animal reproduction studies, icatibant, administered by the subcutaneous route during the period of organogenesis, did not cause structural abnormalities in rats or rabbits; however, premature birth and abortion were observed in rabbits …" }, "verifiedAt": "2026-08-02" }, { "signal": "Across repeated treatment in the controlled trials, 4 patients tested positive for anti-icatibant antibodies, three of whom had subsequent negative tests, and no hypersensitivity or anaphylactic reactions were reported. Postmarketing experience with FIRAZYR has identified urticaria.", "note": "Included because immunogenicity is the open question for every injected peptide on this site, and icatibant is one of the few where it was actually measured in a controlled programme rather than left unstudied. The label's own caveat on the postmarketing entry applies: these events are reported voluntarily from a population of uncertain size, so frequency cannot be reliably estimated and causality cannot be established. FDA's Summary Review is blunter on the trial data — 'Immunogenicity was not an issue with icatibant' — but that assessment covers a safety database FDA itself described as small, 236 unique patients at the time of approval.", "source": { "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/022150s016lbl.pdf", "title": "FIRAZYR (icatibant) Injection, for subcutaneous use — Full Prescribing Information", "publisher": "FDA", "date": "2024-01-19", "quote": "Across repeated treatment in the controlled trials, 4 patients tested positive for anti-icatibant antibodies. Three of these patients had subsequent tests which were negative. No hypersensitivity or anaphylactic reactions were reported with FIRAZYR. … The following adverse reactions have been identified during post approval use of FIRAZYR: urticaria." }, "verifiedAt": "2026-08-02" } ], "faqs": [ { "question": "Is icatibant FDA-approved in 2026?", "answer": "Yes. FDA approved Firazyr (icatibant) injection under NDA 022150 on 25 August 2011, writing in the approval letter that the application 'provides for the use of Firazyr (icatibant) Injection for the treatment of acute attacks of hereditary angioedema in adults 18 years of age and older' and that 'It is approved, effective on the date of this letter'. The application is held today by Takeda Pharmaceuticals U.S.A. and carries prescription marketing status in FDA's product records; six generic icatibant acetate injection products are also approved. Read the indication rather than the approval: icatibant is approved for treating acute attacks of a specific inherited disorder in adults, not for angioedema generally, not for routine prevention of attacks, and not for anyone under 18.", "source": { "url": "https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2011/022150s000ltr.pdf", "title": "NDA 022150 — NDA Approval Letter, Firazyr (icatibant acetate) Injection", "publisher": "FDA", "date": "2011-08-25", "quote": "This new drug application provides for the use of Firazyr (icatibant) Injection for the treatment of acute attacks of hereditary angioedema in adults 18 years of age and older. We have completed our review of this application, as amended. It is approved, effective on the date of this letter, for use as recommended in the enclosed agreed-upon labeling text." }, "verifiedAt": "2026-08-02" }, { "question": "Is Firazyr approved for children?", "answer": "No. The FDA-approved labeling for FIRAZYR confines the indication to 'adults 18 years of age and older', and section 8.4 states that 'Safety and effectiveness in pediatric patients below the age of 18 years have not been established.' That gap is not merely an unstudied box: the same section reports that subcutaneous daily administration of icatibant to young rats during the juvenile period of development delayed the sexual maturation of male reproductive tissues, and that impaired fertility and reproductive performance were also observed in male rats at the end of the postnatal treatment period, effects the label attributes to antagonism of the bradykinin B2 receptor. Note also that the approval letter records the sponsor as EXEMPT from the pediatric assessment normally required under the Pediatric Research Equity Act, because the product carried orphan drug designation for this indication.", "source": { "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/022150s016lbl.pdf", "title": "FIRAZYR (icatibant) Injection, for subcutaneous use — Full Prescribing Information", "publisher": "FDA", "date": "2024-01-19", "quote": "Safety and effectiveness in pediatric patients below the age of 18 years have not been established." }, "verifiedAt": "2026-08-02" }, { "question": "Is icatibant approved for angioedema caused by ACE inhibitors?", "answer": "No. The FDA-approved indication for FIRAZYR is confined to acute attacks of HEREDITARY angioedema in adults, and angioedema induced by an ACE inhibitor is a different condition that is not named in it. The label goes further than silence on this point: section 7.1 states that FIRAZYR 'has the potential to have a pharmacodynamic interaction with ACE inhibitors where FIRAZYR may attenuate the antihypertensive effect of ACE inhibitors' and that 'Clinical trials to date have excluded subjects taking ACE inhibitors.' So the patients most often reached for with icatibant off-label are precisely the patients the approval's evidence base does not contain. The trial that was later run in them is a separate question, answered separately, and it did not go the way the mechanism predicted.", "source": { "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/022150s016lbl.pdf", "title": "FIRAZYR (icatibant) Injection, for subcutaneous use — Full Prescribing Information", "publisher": "FDA", "date": "2024-01-19", "quote": "FIRAZYR is a bradykinin B2 receptor antagonist and thereby has the potential to have a pharmacodynamic interaction with ACE inhibitors where FIRAZYR may attenuate the antihypertensive effect of ACE inhibitors. Clinical trials to date have excluded subjects taking ACE inhibitors." }, "verifiedAt": "2026-08-02" }, { "question": "Did icatibant work for ACE inhibitor-induced angioedema in clinical trials?", "answer": "No — the Phase 3 trial failed. In a randomised, placebo-controlled trial at 31 centers in 4 countries (the CAMEO study, registered as NCT01919801, sponsor Shire), 121 adults on ACE inhibitors presenting within 12 hours of at least moderately severe angioedema were randomised 1:1 to icatibant or placebo. The investigators reported: 'We observed no difference in time to meeting discharge criteria between groups (median, 4.0 hours in each group; P = .63). There also was no difference in time to onset of symptom relief … or any other secondary end point.' Their stated conclusion was that 'Icatibant was no more efficacious than placebo in at least moderately severe ACE-I-induced angioedema of the upper airway.' An earlier and much smaller phase 2 study published in the New England Journal of Medicine in 2015 (Baş et al., 27 patients in the per-protocol population, registered as NCT01154361) had reported a shorter time to complete resolution of edema with icatibant — but that study compared icatibant against a glucocorticoid-plus-antihistamine regimen rather than against placebo, and the larger placebo-controlled trial that followed did not reproduce the result. The authors of the Phase 3 trial noted that more than 90% of their subjects received corticosteroids, antihistamines, or epinephrine before the study drug.", "source": { "url": "https://pubmed.ncbi.nlm.nih.gov/28552382/", "title": "Sinert R, et al. Randomized Trial of Icatibant for Angiotensin-Converting Enzyme Inhibitor-Induced Upper Airway Angioedema. J Allergy Clin Immunol Pract 2017;5(5):1402-1409", "publisher": "PubMed", "date": "2017-05-25", "quote": "We observed no difference in time to meeting discharge criteria between groups (median, 4.0 hours in each group; P = .63). There also was no difference in time to onset of symptom relief … or any other secondary end point. … Icatibant was no more efficacious than placebo in at least moderately severe ACE-I-induced angioedema of the upper airway." }, "verifiedAt": "2026-08-02" }, { "question": "Why did FDA reject Firazyr in 2008 before approving it in 2011?", "answer": "FDA's Division Director wrote that 'The original NDA was submitted in October 2007, and a Not Approval action was taken in April 2008, because substantial evidence of efficacy was not demonstrated in two pivotal studies. The original NDA included one placebo-controlled study that did not show efficacy, and another tranexamic acid (TA) active-controlled study that showed efficacy. Demonstration of efficacy in the TA active-controlled study was not considered adequate for approval because TA is not approved for the treatment of acute attacks of HAE.' The placebo-controlled study was FAST-1, which missed its prespecified primary endpoint (p = 0.142 against placebo for all attacks, per FDA's own table). The sponsor then ran a third trial, FAST-3, also placebo-controlled, which FDA reported was statistically superior to placebo on its prespecified endpoint — and approval followed in August 2011. The reason this is worth knowing is that it is invisible from the label: an approved drug reads as though its evidence arrived clean, and here FDA is on record that it did not.", "source": { "url": "https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022150Orig1s000SumR.pdf", "title": "Summary Review of Regulatory Action — NDA 22-150, Firazyr (icatibant)", "publisher": "FDA", "date": "2011-08-24", "quote": "The original NDA was submitted in October 2007, and a Not Approval action was taken in April 2008, because substantial evidence of efficacy was not demonstrated in two pivotal studies. The original NDA included one placebo-controlled study that did not show efficacy, and another tranexamic acid (TA) active-controlled study that showed efficacy. Demonstration of efficacy in the TA active-controlled study was not considered adequate for approval because TA is not approved for the treatment of acute attacks of HAE." }, "verifiedAt": "2026-08-02" }, { "question": "Is there a generic version of Firazyr?", "answer": "Yes. FDA's Drugs@FDA records list six approved abbreviated new drug applications for icatibant acetate injection alongside the originator NDA 022150, all in prescription marketing status and all carrying therapeutic equivalence code AP: Teva (ANDA 210118, approved 2019-07-15), Jiangsu Hansoh (ANDA 211021, 2020-03-09), Fresenius Kabi (ANDA 208317, 2020-06-18), Cipla (ANDA 212446, 2020-07-13), Eugia (ANDA 213521, 2023-08-14) and Alembic (ANDA 213773, 2024-06-14). Two things follow. A generic is approved as therapeutically equivalent to the reference product for the REFERENCE PRODUCT'S indication, so the arrival of generics widened availability and did not widen the approved use — every one of these is approved for acute attacks of hereditary angioedema in adults. And an approved generic is an approved drug product: none of this says anything about compounded, imported or research-labelled material sold under the same name.", "source": { "url": "https://api.fda.gov/drug/drugsfda.json?search=openfda.generic_name:\"icatibant\"&limit=10", "title": "Drugs@FDA records for icatibant (openFDA drug/drugsfda API)", "publisher": "FDA", "date": "2026-07-31" }, "verifiedAt": "2026-08-02" } ] }, { "slug": "igf-1-lr3", "name": "IGF-1 LR3", "aliases": [ "Long R3 IGF-1", "LongR3-IGF-I", "Long-R³-IGF-I", "IGF-1 Long R3", "long-(Arg3)insulin-like growth factor-I" ], "url": "https://peptides101.com/compounds/igf-1-lr3", "moleculeNote": "IGF-1 LR3 is an engineered ANALOGUE of insulin-like growth factor 1 — it is not insulin-like growth factor 1, and it is not the FDA-approved IGF-1 medicine. A 2026 review in Frontiers in Endocrinology describes it as 'an engineered analogue of IGF-1 characterised by the substitution of glutamic acid with arginine at position 3 and the presence of an additional N-terminal amino acid extension', modifications the authors report as markedly reducing affinity for IGF-1 binding proteins relative to native IGF-1. The approved drug is mecasermin (INCRELEX, BLA 021839), and its FDA labeling states that 'The amino acid sequence of the product is identical to that of endogenous human IGF-1' and that 'IGF-1 consists of 70 amino acids'. Sequence-identical and engineered-analogue are not the same molecule, so mecasermin's approval, its label, and the trials behind it do not describe IGF-1 LR3. A second approved application exists and is also a different molecule: mecasermin rinfabate (IPLEX, BLA 021884), recorded in Drugs@FDA as discontinued. Adjacent research analogues sold under similar names — Des(1-3)-IGF-I and R3-IGF-I — are again distinct substances; anti-doping laboratories treat all three as separate analytes.", "quickAnswer": "IGF-1 LR3 (Long R3 IGF-1) is not an FDA-approved drug and is not the FDA-approved IGF-1 medicine. Drugs@FDA contains exactly two applications for an IGF-1 active ingredient, both for different molecules: mecasermin (INCRELEX, BLA 021839), whose FDA labeling states 'The amino acid sequence of the product is identical to that of endogenous human IGF-1' and which is approved only for growth failure in paediatric patients 2 years and older with severe primary IGF-1 deficiency or GH gene deletion with neutralizing antibodies to GH; and mecasermin rinfabate (IPLEX, BLA 021884), recorded as discontinued. IGF-1 LR3 is instead an engineered analogue carrying an arginine-for-glutamic-acid substitution at position 3 and an N-terminal extension, and a 2026 review in Frontiers in Endocrinology places it in the lowest of its four evidence tiers, stating that IGF-1 LR3 and two other compounds 'have no peer-reviewed human studies and are supported only by preclinical extrapolation and grey-literature user narratives'. IGF-1 LR3 also appears in none of Categories 1, 2 or 3 of FDA's 503A bulk drug substances list updated 14 May 2026, and the World Anti-Doping Agency's 2026 Prohibited List prohibits 'Insulin-like growth factor 1 (IGF-1, mecasermin) and its analogues' at all times, in and out of competition.", "fdaStatus": { "value": "not-approved", "note": "Not an FDA-approved drug for any indication, and not in active development toward approval. Drugs@FDA contains exactly two applications for an IGF-1 active ingredient and neither is this molecule: BLA 021839 (INCRELEX, mecasermin recombinant, Ipsen, marketing status Prescription) and BLA 021884 (IPLEX, mecasermin rinfabate recombinant, Insmed, marketing status Discontinued). 'Not-approved' rather than 'investigational' is a determination, not a default. The investigational tier requires active development by an identifiable sponsor with registered trials, and there is no sponsor and no registration: the ClinicalTrials.gov API v2 was queried on 2026-08-02 for 'IGF-1 LR3', 'Long R3 IGF-1' and 'LR3 IGF-1' and returned totalCount 0 for all three. There is no programme here that stopped; there was never one. This says nothing about whether IGF-1 LR3 is sold — it is, and the anti-doping literature cited on this record documents confiscated vials of it.", "source": { "url": "https://api.fda.gov/drug/drugsfda.json?search=products.active_ingredients.name:\"mecasermin\"&limit=10", "title": "Drugs@FDA (openFDA drug/drugsfda) — applications with an active ingredient named mecasermin", "publisher": "FDA", "date": "2026-07-31" }, "verifiedAt": "2026-08-02" }, "compoundingStatus": null, "evidence": { "tier": "animal-or-in-vitro-only", "humanAdministrationChecked": true, "note": "Administration check RUN, not assumed — and it produced the INVERSE of the MOTS-c trap. The studies here are not endogenous-biomarker studies: they really did administer IGF-1 LR3. They administered it to animals. The search, so it can be repeated: PubMed on 2026-08-02 across five name variants — 'long r3 igf-1', 'IGF-1 LR3', 'LR3 IGF-1', 'Long-R3-IGF-1' and 'LongR3' — with every retrieved record opened. The interventional work is in fetal sheep (Am J Physiol Endocrinol Metab 2021 and 2025; J Dev Orig Health Dis 2023), mice (J Alzheimers Dis 2025), rats (Drug Test Anal 2021; Int J Biol Macromol 2025), guinea pigs, beef heifers and cell culture. The same searches restricted to publication types 'Clinical Trial' or 'Randomized Controlled Trial' returned ZERO records. ClinicalTrials.gov API v2 returned totalCount 0 for all three LR3 name variants, so there is no registration to check sponsor, status or results against — and per this site's policy a registration would not have been evidence anyway. Two independent lines therefore agree: our own search, and a 2026 peer-reviewed review that ran its own literature search to January 2026 and placed IGF-1 LR3 in its lowest evidentiary tier. READ THE LABEL NARROWLY. 'Animal-or-in-vitro-only' means no human administration was found at any level of quality. It does NOT mean the animal work supports the marketing: the most recent interventional study is negative on the growth endpoint, and is recorded under faqs. SCOPE: none of this transfers from, or to, mecasermin. Mecasermin has human trials because it is a different, sequence-identical molecule with an approved label; those trials are evidence about mecasermin.", "source": { "url": "https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2026.1822475/full", "title": "The emerging landscape of performance-enhancing peptides modulating GH-IGF1 axis: bridging the gap between clinical evidence and patient self-administration", "publisher": "Frontiers in Endocrinology", "date": "2026-06-18", "quote": "At the opposite end, CJC-1295 without DAC, PEG-MGF, and IGF-1 LR3 (tier D) have no peer-reviewed human studies and are supported only by preclinical extrapolation and grey-literature user narratives." }, "verifiedAt": "2026-08-02" }, "fdaApproval": null, "fdaFindings": [ { "finding": "Drugs@FDA contains no application for IGF-1 LR3. Searching Drugs@FDA for an IGF-1 active ingredient returns exactly two applications, both for different molecules: BLA 021839 (INCRELEX, mecasermin recombinant, Ipsen Inc, marketing status Prescription) and BLA 021884 (IPLEX, mecasermin rinfabate recombinant, Insmed, marketing status Discontinued).", "note": "The URL is the query itself, so this negative is checkable rather than asserted. It was cross-run against `openfda.generic_name`, `openfda.substance_name` and `products.brand_name`, each of which returns only these same approved mecasermin products, and against LR3-specific terms, which return NOT_FOUND on every field. Both directions matter: an openFDA record's `openfda` block is sometimes EMPTY, so a query touching only that block can fail for reasons having nothing to do with the substance. A NOT_FOUND from a single badly-shaped query is an artifact of the query — that exact mistake produced a false 'sermorelin is not in Drugs@FDA' claim in this library — so the positive hits above are load-bearing: they prove the query shape finds IGF-1 substances when they exist. Per Drugs@FDA, INCRELEX was originally approved 2005-08-30 as a Type 1 New Molecular Entity with priority review and orphan designation, and the submission records carry the note 'This Former NDA Was Deemed To Be a BLA on March 23, 2020.' IPLEX was originally approved 2005-12-12 and is recorded as discontinued; this record does not state why, because we have not opened a document that says.", "source": { "url": "https://api.fda.gov/drug/drugsfda.json?search=products.active_ingredients.name:\"mecasermin\"&limit=10", "title": "Drugs@FDA (openFDA drug/drugsfda) — applications with an active ingredient named mecasermin", "publisher": "FDA", "date": "2026-07-31" }, "verifiedAt": "2026-08-02" }, { "finding": "The FDA-approved IGF-1 product is a different molecule. INCRELEX (mecasermin) labeling states: 'Mecasermin is a human insulin-like growth factor-1 (rhIGF-1) produced by recombinant DNA technology. IGF-1 consists of 70 amino acids in a single chain with three intramolecular disulfide bridges and a molecular weight of 7649 Da. The amino acid sequence of the product is identical to that of endogenous human IGF-1.'", "note": "Recorded verbatim because it is the sentence that settles the disambiguation, and it comes from FDA-approved labeling rather than from us. The approved molecule is defined by being IDENTICAL to endogenous human IGF-1. IGF-1 LR3 is defined by NOT being identical to it — an arginine-for-glutamic-acid substitution at position 3 plus an N-terminal extension, engineered specifically to escape the binding proteins that regulate native IGF-1. Whatever one thinks of that design, it is the opposite of the property this label describes.", "source": { "url": "https://www.accessdata.fda.gov/spl/data/52199e09-74a6-6144-e063-6294a90a59e7/52199e09-74a6-6144-e063-6294a90a59e7.xml", "title": "INCRELEX (mecasermin) injection — Highlights of Prescribing Information (SPL)", "publisher": "FDA", "date": "2026-05-18", "quote": "Mecasermin is a human insulin-like growth factor-1 (rhIGF-1) produced by recombinant DNA technology. IGF-1 consists of 70 amino acids in a single chain with three intramolecular disulfide bridges and a molecular weight of 7649 Da. The amino acid sequence of the product is identical to that of endogenous human IGF-1." }, "verifiedAt": "2026-08-02" }, { "finding": "The approved indication for INCRELEX is narrow and paediatric: 'INCRELEX (mecasermin) injection is indicated for the treatment of growth failure in pediatric patients 2 years of age and older with severe primary IGF-1 deficiency or with growth hormone (GH) gene deletion who have developed neutralizing antibodies to GH.' The label adds a limitation of use — 'INCRELEX is not a substitute to GH for approved GH indications' — and states it 'is not indicated for use in patients with secondary forms of IGF-1 deficiency, such as GH deficiency, malnutrition, hypothyroidism, or chronic treatment with pharmacologic doses of anti-inflammatory corticosteroids.'", "note": "This is the gap that makes 'IGF-1 is FDA-approved' misleading even when it is true. The approval is for growth failure in children with a rare, defined deficiency confirmed by a height standard deviation score at or below -3.0 AND a basal IGF-1 standard deviation score at or below -3.0 with normal or elevated growth hormone. It is not an approval for muscle gain, recovery, or anti-aging in adults, and the label expressly excludes SECONDARY IGF-1 deficiency — which is the category most adults with a low IGF-1 reading would fall into. This finding is about mecasermin. It is recorded on the IGF-1 LR3 record because the halo it generates is the thing IGF-1 LR3 is sold under.", "source": { "url": "https://www.accessdata.fda.gov/spl/data/52199e09-74a6-6144-e063-6294a90a59e7/52199e09-74a6-6144-e063-6294a90a59e7.xml", "title": "INCRELEX (mecasermin) injection — Highlights of Prescribing Information (SPL)", "publisher": "FDA", "date": "2026-05-18", "quote": "INCRELEX (mecasermin) injection is indicated for the treatment of growth failure in pediatric patients 2 years of age and older with severe primary IGF-1 deficiency or with growth hormone (GH) gene deletion who have developed neutralizing antibodies to GH. … INCRELEX is not indicated for use in patients with secondary forms of IGF-1 deficiency, such as GH deficiency, malnutrition, hypothyroidism, or chronic treatment with pharmacologic doses of anti-inflammatory corticosteroids." }, "verifiedAt": "2026-08-02" }, { "finding": "IGF-1 LR3 appears in none of Categories 1, 2 or 3 of FDA's 503A bulk drug substances list updated 2026-05-14. The document returns no hit for 'IGF', 'insulin-like', 'mecasermin', 'LR3' or 'long R3' anywhere.", "note": "Recorded to close a misreading, not to assert a status. Verified by fetching the document with a browser user-agent and text-extracting it: zero hits for 'IGF', 'insulin-like', 'mecasermin', 'LR3' or 'long R3' anywhere in the seven pages. The extraction was validated rather than trusted — the six known Category 2 substances (cesium chloride, domperidone, germanium sesquioxide, ibutamoren mesylate, kisspeptin-10 and quinacrine hydrochloride) are all present in the extracted text, so the absence is an absence and not a broken parse. WHAT THIS DOES AND DOES NOT ESTABLISH. It establishes that IGF-1 LR3 is in none of the three categories, which is why this record carries no compoundingStatus: absence alone cannot tell 'nominated then withdrawn' apart from 'never nominated', and no docket entry or briefing document exists for this substance to settle it. It is not permission and it is not a safety finding. Note also what IS in the list, one line away in Category 3 and frequently confused with this compound: 'Mechano growth factor (MGF)', an IGF-1 splice variant and a different substance again. FDA's companion safety-risks page separately publishes a concern for pegylated MGF; it publishes nothing about IGF-1 LR3.", "source": { "url": "https://www.fda.gov/media/94155/download", "title": "Bulk Drug Substances Nominated for Use in Compounding Under Section 503A of the Federal Food, Drug, and Cosmetic Act", "publisher": "FDA", "date": "2026-05-14" }, "verifiedAt": "2026-08-02" } ], "safetySignals": [ { "signal": "In a 2023 study, researchers infusing IGF-1 LR3 into late-gestation fetal sheep reported that fetal plasma insulin concentrations decreased and that insulin concentrations during a hyperglycemic clamp were 66% lower with IGF-1 LR3 infusion than with control.", "note": "Attributed to the study, and the species is not a footnote — these are fetal sheep, infused directly into the fetal circulation, and nothing about the finding can be carried to an adult human. It is recorded because it runs against the market's mental model of IGF-1 LR3 as a purely anabolic agent: the measured effect here is on insulin secretion. The same group reported in 2021 that a one-week infusion produced reduced glucose-stimulated insulin secretion attributable to an intrinsic islet defect, and in 2023 that isolated islets recovered after an acute infusion. Read as a signal worth knowing about, not as a human safety finding — there is no human safety data to weigh it against.", "source": { "url": "https://pubmed.ncbi.nlm.nih.gov/37114757/", "title": "Attenuated glucose-stimulated insulin secretion during an acute IGF-1 LR3 infusion into fetal sheep does not persist in isolated islets", "publisher": "Journal of Developmental Origins of Health and Disease", "date": "2023-06-01", "quote": "Fetal plasma insulin concentrations decreased with IGF-1 LR3 infusion (P < 0.05), and insulin concentrations during the hyperglycemic clamp were 66% lower with IGF-1 LR3 infusion compared to CON (P < 0.0001)." }, "verifiedAt": "2026-08-02" }, { "signal": "An anti-doping laboratory analysing a confiscated injection vial identified its contents as His-tagged Long-R³-IGF-I — a purification construct, not the substance a purchaser would expect — and reported that the effects of that molecule in humans have not been described.", "note": "The cleanest product-identity finding on this record, and it cuts deeper than 'underdosed or fake'. A His₆-tag is added during recombinant production to allow purification and is normally cleaved off; the authors' reading is that this vial held material made for biochemical laboratory work and diverted into an injection vial. So the question is not only whether a vial labelled IGF-1 LR3 contains IGF-1 LR3 — it is that even when the core sequence matches, the molecule in the vial may carry an appendage with no described human effects at all. The same laboratory's 2009 survey of confiscated products separately reported unpurified long-R(3)-IGF-1 among its findings.", "source": { "url": "https://pubmed.ncbi.nlm.nih.gov/20675162/", "title": "Detection of His-tagged Long-R³-IGF-I in a black market product", "publisher": "Growth Hormone & IGF Research", "date": "2010-10-01", "quote": "(Tandem) mass spectra characterized the protein as Long-R³-IGF-I with a His₆-tag attached to the C-terminus by the linker amino acids Leu-Glu. … The effects of His-tagged Long-R³-IGF-I in humans have not been elucidated or described and the product may rather be a by-product from biochemical studies than synthesized for injection purposes." }, "verifiedAt": "2026-08-02" }, { "signal": "In a 2021 anti-doping method paper, the authors state that IGF-I and its analogs LongR3-IGF-I, Des(1-3)-IGF-I and R3-IGF-I 'were never approved for use in humans' while being 'readily available as black market products for bodybuilding', and report that 'Abundant signs of lower quality, oxidized peptide forms were found in black market products'.", "note": "A quality finding, not a pharmacology finding — and the reason it belongs here is that oxidation is invisible to the checks purchasers actually run. The authors did not go looking for degraded product; they had to add mono-oxidized forms to their detection method because the black-market material contained them. Note also what the paper's own animal work found about persistence: after a single intramuscular administration in rats, unchanged LongR3-IGF-I 'disappeared rapidly after 4 h', while several N-terminal degradation products persisted longer. The 'never approved for use in humans' clause is the authors' statement; this record verifies the same point independently against Drugs@FDA above rather than resting on it.", "source": { "url": "https://pubmed.ncbi.nlm.nih.gov/33587816/", "title": "Detection of LongR3-IGF-I, Des(1-3)-IGF-I, and R3-IGF-I using immunopurification and high resolution mass spectrometry for antidoping purposes", "publisher": "Drug Testing and Analysis", "date": "2021-07-01", "quote": "Insulin-like growth factor-I (IGF-I) and its analogs LongR3-IGF-I, Des(1-3)-IGF-I, and R3-IGF-I are prohibited substances in sport. Although they were never approved for use in humans, they are readily available as black market products for bodybuilding and can be used to enhance physical performance. … Abundant signs of lower quality, oxidized peptide forms were found in black market products, justifying the need to monitor at least both the native and mono-oxidized forms." }, "verifiedAt": "2026-08-02" }, { "signal": "A 2026 review states that claims about IGF-1 analogues including IGF-1 LR3 'rest on extrapolation rather than direct human data', that clinicians 'should treat exposure to these compounds as evidence-poor', and that concern about long-term cancer risk from exogenous IGF-1 analogues 'should be presented as theoretical but clinically relevant, especially in the absence of long-term safety data for off-label IGF-1 analogue use'.", "note": "Reproduced with its hedges intact, because the hedges are the finding. The authors do NOT claim IGF-1 LR3 causes cancer; they describe a theoretical concern drawn from epidemiologic associations between higher circulating IGF-1 and several cancers, and from IGF-1 receptor signalling being a well-characterised proliferative pathway in oncology models. Stripping the hedge in either direction misreports them: 'IGF-1 LR3 causes cancer' overstates it, and 'no evidence of harm' misreads an absence of studies as a negative result. Their own summary table records 'No peer-reviewed human studies' in the adverse-effects column for IGF-1 LR3 — there is no human safety profile to report, which is a different statement from a clean one.", "source": { "url": "https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2026.1822475/full", "title": "The emerging landscape of performance-enhancing peptides modulating GH-IGF1 axis: bridging the gap between clinical evidence and patient self-administration", "publisher": "Frontiers in Endocrinology", "date": "2026-06-18", "quote": "claims about IGF-1 analogues (PEG-MGF, IGF-1 LR3) and CJC-1295 without DAC rest on extrapolation rather than direct human data; clinicians should treat exposure to these compounds as evidence-poor and frame counselling accordingly. … This risk framing should be presented as theoretical but clinically relevant, especially in the absence of long-term safety data for off-label IGF-1 analogue use." }, "verifiedAt": "2026-08-02" }, { "signal": "The FDA-approved IGF-1 product mecasermin (INCRELEX) — a different molecule from IGF-1 LR3, recorded here for contrast — carries contraindications for closed epiphyses and for malignant neoplasia or a history of malignancy, and its labeling lists hypoglycemia, hypersensitivity including anaphylaxis, intracranial hypertension, tonsillar and adenoidal hypertrophy, slipped capital femoral epiphysis and progression of preexisting scoliosis among serious adverse reactions.", "note": "Recorded on this record for one reason: IGF-1 is marketed as a benign endogenous molecule, and the one IGF-1 product FDA has actually reviewed is contraindicated in malignancy and reports hypoglycemia at high frequency in its trials. SCOPE, and it runs in both directions: these are mecasermin's labeled risks in a paediatric deficiency population, and they cannot be transferred to IGF-1 LR3 in adults as if they were its safety profile. What they establish is narrower and still worth stating — that FDA's own review of an IGF-1 drug did not conclude it was risk-free, and that a purchaser of an unapproved analogue is never asked the screening questions this label requires, because there is no label to ask them.", "source": { "url": "https://www.accessdata.fda.gov/spl/data/52199e09-74a6-6144-e063-6294a90a59e7/52199e09-74a6-6144-e063-6294a90a59e7.xml", "title": "INCRELEX (mecasermin) injection — Highlights of Prescribing Information (SPL)", "publisher": "FDA", "date": "2026-05-18", "quote": "Known Hypersensitivity to mecasermin (4) Closed Epiphyses (4) Malignant Neoplasia (4) … INCRELEX is contraindicated in pediatric patients with malignant neoplasia or a history of malignancy" }, "verifiedAt": "2026-08-02" } ], "faqs": [ { "question": "Is IGF-1 LR3 FDA approved?", "answer": "No. IGF-1 LR3 has no FDA application of any kind. Searching Drugs@FDA for an IGF-1 active ingredient returns exactly two applications, and both are different molecules: BLA 021839 (INCRELEX, mecasermin recombinant, Ipsen, marketing status Prescription) and BLA 021884 (IPLEX, mecasermin rinfabate recombinant, Insmed, marketing status Discontinued). Queries against the generic-name, substance-name and brand-name fields return only those same approved mecasermin products, and every query for the LR3 analogue returns no matches on any field. IGF-1 LR3 is also not in clinical development: ClinicalTrials.gov returned zero registered studies for 'IGF-1 LR3', 'Long R3 IGF-1' and 'LR3 IGF-1' when queried on 2 August 2026, so there is no sponsor and no registered trial to point at. Being unapproved says nothing about whether it is sold — it is.", "source": { "url": "https://api.fda.gov/drug/drugsfda.json?search=products.active_ingredients.name:\"mecasermin\"&limit=10", "title": "Drugs@FDA (openFDA drug/drugsfda) — applications with an active ingredient named mecasermin", "publisher": "FDA", "date": "2026-07-31" }, "verifiedAt": "2026-08-02" }, { "question": "Is IGF-1 LR3 the same thing as Increlex or mecasermin?", "answer": "No — they are different molecules, and the FDA-approved label says so on its face. INCRELEX (mecasermin) labeling states that 'IGF-1 consists of 70 amino acids in a single chain with three intramolecular disulfide bridges and a molecular weight of 7649 Da' and that 'The amino acid sequence of the product is identical to that of endogenous human IGF-1.' IGF-1 LR3 is defined by not being identical: it carries an arginine substituted for glutamic acid at position 3 plus an additional N-terminal extension, engineered to reduce binding to the IGF-1 binding proteins that regulate the native hormone. Because they are different molecules, mecasermin's approval, its prescribing information and the clinical trials behind it describe mecasermin and do not describe IGF-1 LR3. The approved indication is also far narrower than the market implies: INCRELEX is indicated 'for the treatment of growth failure in pediatric patients 2 years of age and older with severe primary IGF-1 deficiency or with growth hormone (GH) gene deletion who have developed neutralizing antibodies to GH', and the label states it 'is not indicated for use in patients with secondary forms of IGF-1 deficiency'.", "source": { "url": "https://www.accessdata.fda.gov/spl/data/52199e09-74a6-6144-e063-6294a90a59e7/52199e09-74a6-6144-e063-6294a90a59e7.xml", "title": "INCRELEX (mecasermin) injection — Highlights of Prescribing Information (SPL)", "publisher": "FDA", "date": "2026-05-18", "quote": "The amino acid sequence of the product is identical to that of endogenous human IGF-1. … INCRELEX (mecasermin) injection is indicated for the treatment of growth failure in pediatric patients 2 years of age and older with severe primary IGF-1 deficiency or with growth hormone (GH) gene deletion who have developed neutralizing antibodies to GH." }, "verifiedAt": "2026-08-02" }, { "question": "Are there any human studies on IGF-1 LR3?", "answer": "No peer-reviewed human studies of IGF-1 LR3 have been identified. A 2026 narrative review in Frontiers in Endocrinology, which ran its own literature search to January 2026, assigns IGF-1 LR3 to the lowest of its four evidentiary tiers and states that IGF-1 LR3, PEG-MGF and CJC-1295 without DAC 'have no peer-reviewed human studies and are supported only by preclinical extrapolation and grey-literature user narratives', adding that 'Mechanistic plausibility for tier-D compounds does not constitute clinical evidence and should not be interpreted as such.' An independent search on 2 August 2026 reached the same result: across five name variants, every interventional study retrieved from PubMed administered IGF-1 LR3 to animals — fetal sheep, mice, rats, guinea pigs, cattle — or to cells in culture, the same searches restricted to clinical-trial and randomised-controlled-trial publication types returned zero records, and ClinicalTrials.gov returned zero registered studies. The absence of human studies is not the same as evidence of safety, and it is not the same as evidence of harm.", "source": { "url": "https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2026.1822475/full", "title": "The emerging landscape of performance-enhancing peptides modulating GH-IGF1 axis: bridging the gap between clinical evidence and patient self-administration", "publisher": "Frontiers in Endocrinology", "date": "2026-06-18", "quote": "IGF-1 LR3 is an engineered analogue of IGF-1 characterised by the substitution of glutamic acid with arginine at position 3 and the presence of an additional N-terminal amino acid extension. … CJC-1295 without DAC, PEG-MGF, and IGF-1 LR3 (tier D) have no peer-reviewed human studies and are supported only by preclinical extrapolation and grey-literature user narratives." }, "verifiedAt": "2026-08-02" }, { "question": "Is IGF-1 LR3 banned in sport?", "answer": "Yes. The World Anti-Doping Agency's 2026 Prohibited List, effective 1 January 2026, prohibits 'Insulin-like growth factor 1 (IGF-1, mecasermin) and its analogues' under S2.3, Growth Factors and Growth Factor Modulators. IGF-1 LR3 is an IGF-1 analogue and falls inside that wording; the List is also written to catch substances it does not name, stating that 'The following substances, and other substances with similar chemical structure or similar biological effect(s), are prohibited.' Class S2 is prohibited at all times, both in and out of competition, and the List records that 'All prohibited substances in this class are non-Specified Substances', which is the category carrying the least scope for a reduced sanction. Anti-doping laboratories have published a validated method that distinguishes LongR3-IGF-I from the related analogues Des(1-3)-IGF-I and R3-IGF-I, so a detection method for this specific molecule exists in the literature — which is not the same as a statement about how often it is applied.", "source": { "url": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "title": "The 2026 Prohibited List — World Anti-Doping Code International Standard", "publisher": "World Anti-Doping Agency", "date": "2026-01-01", "quote": "Insulin-like growth factor 1 (IGF-1, mecasermin) and its analogues … and other growth factors or growth factor modulators affecting muscle, tendon or ligament protein synthesis/degradation, vascularisation, energy utilization, regenerative capacity or fibre type switching." }, "verifiedAt": "2026-08-02" }, { "question": "Can a compounding pharmacy legally make IGF-1 LR3?", "answer": "Not under section 503A. IGF-1 LR3 does not appear anywhere in FDA's list of bulk drug substances nominated for use in compounding under section 503A, updated 14 May 2026 — not in Category 1, not in Category 2, not in Category 3. A bulk drug substance that is neither the subject of an applicable USP or NF monograph nor a component of an FDA-approved drug must appear on the 503A bulks list to be used in 503A compounding, and IGF-1 LR3 appears on it in no category. Read the absence precisely: it is not a legalisation, it is not a safety finding, and it does not tell you whether IGF-1 LR3 was ever nominated and withdrawn or was simply never nominated at all — which is why this record carries no 503A category rather than guessing one. Note that a nearby entry is routinely confused with this compound: 'Mechano growth factor (MGF)' does appear in the list, and it is an IGF-1 splice variant, not IGF-1 LR3.", "source": { "url": "https://www.fda.gov/media/94155/download", "title": "Bulk Drug Substances Nominated for Use in Compounding Under Section 503A of the Federal Food, Drug, and Cosmetic Act", "publisher": "FDA", "date": "2026-05-14" }, "verifiedAt": "2026-08-02" }, { "question": "What is actually in a vial sold as IGF-1 LR3?", "answer": "Not necessarily IGF-1 LR3, and not necessarily only IGF-1 LR3. In a 2010 case report, an anti-doping laboratory analysed a confiscated injection vial and identified the contents by mass spectrometry as 'Long-R³-IGF-I with a His₆-tag attached to the C-terminus by the linker amino acids Leu-Glu' — a purification construct of the kind added during recombinant protein production for laboratory work and normally removed. The authors wrote that 'The effects of His-tagged Long-R³-IGF-I in humans have not been elucidated or described and the product may rather be a by-product from biochemical studies than synthesized for injection purposes.' Separately, a 2021 anti-doping method paper reported that 'Abundant signs of lower quality, oxidized peptide forms were found in black market products', and a 2009 laboratory survey reported unpurified long-R(3)-IGF-1 among confiscated items. The point is narrower than 'fakes exist': even when the core sequence matches, the molecule in the vial may carry modifications with no described human effects at all.", "source": { "url": "https://pubmed.ncbi.nlm.nih.gov/20675162/", "title": "Detection of His-tagged Long-R³-IGF-I in a black market product", "publisher": "Growth Hormone & IGF Research", "date": "2010-10-01", "quote": "(Tandem) mass spectra characterized the protein as Long-R³-IGF-I with a His₆-tag attached to the C-terminus by the linker amino acids Leu-Glu. … The effects of His-tagged Long-R³-IGF-I in humans have not been elucidated or described and the product may rather be a by-product from biochemical studies than synthesized for injection purposes." }, "verifiedAt": "2026-08-02" }, { "question": "Does IGF-1 LR3 build muscle?", "answer": "No study in humans has tested that question. The most recent interventional study of IGF-1 LR3 is in fetal sheep and is negative on its growth endpoint: researchers reported in the American Journal of Physiology — Endocrinology and Metabolism in 2025 that 'a 1-wk IGF-1 LR3 treatment did not improve growth in FGR fetuses' after treating growth-restricted fetal sheep, and that 'IGF-1 LR3 treatment administered directly into growth-restricted fetal sheep circulation did not improve fetal growth'. They also reported that circulating amino acids, notably branched-chain amino acids, decreased with treatment. That finding is about growth-restricted fetal sheep and cannot be carried across to adults, in either direction — but it is the opposite of a supportive result, and it is the highest-quality interventional evidence that exists for this compound. The mechanistic case for IGF-1 LR3 rests on IGF-1 receptor signalling being well characterised in cell and oncology models, which a 2026 review in Frontiers in Endocrinology — cited separately on this record, not in the study quoted here — describes as plausibility rather than clinical evidence.", "source": { "url": "https://pubmed.ncbi.nlm.nih.gov/39679943/", "title": "IGF-1 LR3 does not promote growth in late-gestation growth-restricted fetal sheep", "publisher": "American Journal of Physiology — Endocrinology and Metabolism", "date": "2025-01-01", "quote": "In summary, a 1-wk IGF-1 LR3 treatment did not improve growth in FGR fetuses. … IGF-1 LR3 treatment administered directly into growth-restricted fetal sheep circulation did not improve fetal growth or attenuate circulating insulin or fetal GSIS." }, "verifiedAt": "2026-08-02" } ] }, { "slug": "ipamorelin", "name": "Ipamorelin", "aliases": [ "Ipamorelin acetate", "NNC 26-0161" ], "url": "https://peptides101.com/compounds/ipamorelin", "moleculeNote": "A synthetic pentapeptide growth hormone secretagogue (ghrelin receptor / GHS-R1a agonist), first identified in 1998. FDA evaluates two distinct substances: ipamorelin (free base) and ipamorelin acetate, and voted on them separately. The distinction is not pedantry — FDA's own briefing document repeatedly flags that the published literature 'does not always clearly identify whether the ipamorelin form administered in the clinical studies was a salt formulation or the free base', and FDA therefore labels the form in the human trials as 'unspecified'. Both nominations were themselves ambiguous about which substance was being nominated. Ipamorelin (free base) is a five-amino-acid peptide containing UNNATURAL amino acids, which FDA treats as a characterisation and immunogenicity concern in its own right.", "quickAnswer": "Ipamorelin is not an FDA-approved drug for any use and is not a component of one, and FDA's Pharmacy Compounding Advisory Committee has already voted it down — 0 yes, 12 no, 1 abstain, voted separately for ipamorelin (free base) and for ipamorelin acetate on 2024-10-29 — against adding either to the 503A bulks list; it is absent from that list today because the committee voted against adding it and the nominators then withdrew the nominations, not because it was cleared, and ipamorelin acetate remains in FDA's Category 2 of bulk drug substances that may present significant safety risks. Ipamorelin genuinely was tested in humans, and it failed: in a 2014 Phase 2 trial of 114 bowel-resection patients, researchers reported no significant differences between ipamorelin and placebo in the key and secondary efficacy analyses, and the development programme was discontinued. FDA has not identified data supporting effectiveness for growth hormone deficiency or for postoperative ileus — the only two uses it evaluated. The uses ipamorelin is actually marketed for, including weight loss, anti-aging and bodybuilding, were never evaluated at all.", "fdaStatus": { "value": "not-approved", "note": "Not an FDA-approved drug for any indication, and not in active development toward approval. That says nothing about whether it is sold — it is.", "source": { "url": "https://www.fda.gov/drugs/human-drug-compounding/certain-bulk-drug-substances-use-compounding-may-present-significant-safety-risks", "title": "Certain Bulk Drug Substances for Use in Compounding that May Present Significant Safety Risks", "publisher": "FDA", "date": "2026-05-14", "quote": "Bulk drug substances nominated but withdrawn" }, "verifiedAt": "2026-07-16" }, "compoundingStatus": { "value": "withdrawn-from-nomination", "note": "Absent from Categories 1, 2 and 3 of the 503A list updated 2026-05-14 — verified by fetching and text-extracting the document directly. Category 2 there contains exactly six substances, and ipamorelin is not among them. The 503A nominations (Wells Pharmacy Network, FDA-2015-N-3534-0283; LDT Health Solutions, FDA-2018-N-2973-0002) were withdrawn by the nominators. THIS IS NOT A LEGALISATION EVENT and, for ipamorelin specifically, the 'it left Category 2' framing is at its most misleading: ipamorelin acetate REMAINS in Category 2 under the 503B interim policy (added 2023-09-29) and is the only substance FDA lists in both its current category 2 table and its withdrawn table. It is not on the 503A bulks list and remains non-compoundable. Withdrawal also came AFTER the advisory committee had already voted the substance down 0-12-1 — the nomination was not withdrawn from a live process with an open outcome. We did not verify the exact withdrawal date; FDA publishes no date column for the withdrawn table.", "source": { "url": "https://www.fda.gov/drugs/human-drug-compounding/certain-bulk-drug-substances-use-compounding-may-present-significant-safety-risks", "title": "Certain Bulk Drug Substances for Use in Compounding that May Present Significant Safety Risks", "publisher": "FDA", "date": "2026-05-14", "quote": "Bulk drug substances nominated but withdrawn" }, "verifiedAt": "2026-07-16" }, "evidence": { "tier": "promising-but-unproven", "humanAdministrationChecked": true, "note": "Administration check run on each cited study, and both PASS — unlike MOTS-c and TB-500, ipamorelin really was administered to humans. Beck et al. 2014 (NCT00672074) gave intravenous ipamorelin or placebo to 114 analysed adults after bowel resection; the earlier Phase 1 (PMID 10496658) gave intravenous infusions across five ascending dose levels to healthy male volunteers (FDA describes it as 48 subjects), and FDA reports that ipamorelin 'displayed linear pharmacokinetics based on the two-compartment model' and that 'a linear pharmacodynamic model described the stimulation of GH release in an episodic fashion dependent on the concentration of ipamorelin'. We do not call that release dose-proportional: FDA does not use the term, and it records that the lowest-dose and placebo groups 'were not included in the PK/PD analysis due to negligible GH levels', which cuts against proportionality at the bottom of the range. Neither is an endogenous-biomarker study. THE TIER LABEL FLATTERS THIS COMPOUND AND SHOULD BE READ WITH THE NOTE, NOT WITHOUT IT. 'Promising-but-unproven' is the correct bucket only because the enum defines it to include programmes that were tested and failed. The honest statement is stronger and worse: the one indication ever tested for efficacy in humans was tested properly and the drug did not beat placebo. In a 2014 Phase 2 trial of 114 bowel-resection patients, researchers reported median time to first tolerated meal of 25.3 hours on ipamorelin versus 32.6 hours on placebo (p = 0.15) and no significant differences in the key or secondary efficacy analyses. Limitations, in the authors' own framing: the study was small and enrolled patients with a broad range of underlying conditions. A larger Phase 2 followed (NCT01280344, Helsinn Therapeutics, n=320, completed) and its results were NEVER posted to ClinicalTrials.gov and never published — we searched all 53 PubMed records mentioning ipamorelin and found no publication reporting it. The programme was then abandoned; no Phase 3 exists. There is zero human efficacy evidence for growth hormone deficiency, and zero for any of the uses ipamorelin is actually marketed for (weight loss, anti-aging, sleep, bodybuilding). FDA: 'FDA has not identified data to support the effectiveness of ipamorelin (free base) or ipamorelin acetate for the diagnosis or treatment of GHD in children or adults.' Both Phase 2 trials were sponsored by Helsinn Therapeutics, a legitimate pharmaceutical company — not by a research-peptide vendor — and both are recorded as COMPLETED with zero results posted.", "source": { "url": "https://pubmed.ncbi.nlm.nih.gov/25331030/", "title": "Prospective, randomized, controlled, proof-of-concept study of the Ghrelin mimetic ipamorelin for the management of postoperative ileus in bowel resection patients", "publisher": "PubMed", "date": "2014-10-21", "quote": "There were no significant differences between ipamorelin and placebo in the key and secondary efficacy analyses." }, "verifiedAt": "2026-07-16" }, "fdaApproval": null, "fdaFindings": [ { "finding": "The Pharmacy Compounding Advisory Committee voted AGAINST placing ipamorelin on the 503A Bulks List on 2024-10-29 — ipamorelin (free base) 0 yes / 12 no / 1 abstain, and ipamorelin acetate 0 yes / 12 no / 1 abstain.", "note": "This is the single most important distinction between ipamorelin and every pending peptide in this library. BPC-157, epitalon, KPV, MOTS-c, semax, TB-500 and emideltide are subject to a staff PROPOSAL awaiting the 2026-07-23 PCAC meeting, and for those a proposal is not a final determination. Ipamorelin's committee process ALREADY RAN and it lost, unanimously among voting members, twice. Committee members who voted no 'agreed that there was a lack of information supporting safety and efficacy shown in the available data for the use of Ipamorelin (free base) for GHD and postoperative ileus'. One member noted 'that the high frequency of a drug being prescribed does not necessarily mean the drug is safe and effective'. The single abstention was not a dissent on the merits: that member cited confusion between the deliberations on ipamorelin acetate and the data presented. Note the committee is advisory — the vote is a recommendation, not a rulemaking.", "source": { "url": "https://www.fda.gov/media/185412/download", "title": "Final Summary Minutes of the Pharmacy Compounding Advisory Committee Meeting, October 29, 2024", "publisher": "FDA", "date": "2024-10-29", "quote": "The majority of the Committee members voted against placing Ipamorelin (free base) on the 503A Bulks List." }, "verifiedAt": "2026-07-16" }, { "finding": "FDA staff proposed not adding ipamorelin acetate or ipamorelin (free base) to the 503A Bulks List, citing lack of data, safety issues, lack of evidence of effectiveness, and the existence of FDA-approved drugs for both proposed conditions.", "note": "The 'existence of FDA-approved drugs' limb matters and is routinely omitted by vendors: FDA's reasoning is partly that patients do not need a compounded ipamorelin because approved options exist (human growth hormone formulations for GHD, and alvimopan, which FDA calls the only approved drug for management of POI), 'particularly in light of these being serious conditions'. Note also the scope, which the next finding records in full: FDA evaluated ipamorelin for growth hormone deficiency and postoperative ileus ONLY, and postoperative ileus was not even nominated — FDA states it 'in its discretion opted to evaluate the unnominated use of postoperative ileus'. None of the uses ipamorelin is actually sold for was evaluated.", "source": { "url": "https://www.fda.gov/media/182088/download", "title": "Ipamorelin-Related Bulk Drug Substances (Ipamorelin (free base) and Ipamorelin Acetate) — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, October 29, 2024", "publisher": "FDA", "date": "2024-10-29", "quote": "Accordingly, we propose not adding ipamorelin acetate or ipamorelin (free base) to the 503A Bulks List." }, "verifiedAt": "2026-07-16" }, { "finding": "FDA evaluated ipamorelin for exactly two uses — growth hormone deficiency and postoperative ileus — and only the first was nominated. None of the uses ipamorelin is actually marketed for was evaluated, so FDA made no effectiveness finding on any of them.", "note": "Three FDA sentences fix the scope. The nominated use: 'The nominators' proposed use for ipamorelin is to treat GHD.' The second condition, added by FDA itself: 'Consistent with past practice, FDA in its discretion opted to evaluate the unnominated use of postoperative ileus.' And the marketed uses, which FDA merely LISTS and never evaluates: 'It has been marketed for use in weight loss management, anti-aging, inflammatory conditions, sleep cycle improvement, and bodybuilding.' FDA's two effectiveness conclusions are scoped word-for-word to GHD and to POI respectively and to nothing else. We do not know why no marketed use was evaluated and FDA does not say, so we do not assert a reason.", "source": { "url": "https://www.fda.gov/media/182088/download", "title": "Ipamorelin-Related Bulk Drug Substances (Ipamorelin (free base) and Ipamorelin Acetate) — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, October 29, 2024", "publisher": "FDA", "date": "2024-10-29", "quote": "Ipamorelin (free base) and ipamorelin acetate were evaluated for the following uses: growth hormone deficiency (GHD) and postoperative ileus (POI)." }, "verifiedAt": "2026-07-16" }, { "finding": "FDA found no effectiveness data for ipamorelin via the subcutaneous route — the very route proposed in the nominations and the one used by the market.", "note": "The nominated product was a 2000 mcg/mL lyophilised powder for SUBCUTANEOUS injection, yet every human study FDA could find used the INTRAVENOUS route. In FDA's words: 'We do not have nonclinical and clinical safety data or effectiveness data for GHD or POI for the proposed SC ROA.' So the human evidence base, such as it is, does not even cover how the substance is administered in practice. FDA's compounding-history finding cuts the same way: outsourcing-facility reporting shows compounding with ipamorelin from 2017, but it 'appears to have stopped in 2020', while FDA separately records that ipamorelin 'formulations are increasingly being marketed by medical spas and wellness clinics' for weight loss management, anti-aging, inflammatory conditions, sleep cycle improvement and bodybuilding. FDA made no effectiveness finding on any of those uses — as the scope finding above records, it did not evaluate them.", "source": { "url": "https://www.fda.gov/media/182088/download", "title": "Ipamorelin-Related Bulk Drug Substances (Ipamorelin (free base) and Ipamorelin Acetate) — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, October 29, 2024", "publisher": "FDA", "date": "2024-10-29" }, "verifiedAt": "2026-07-16" }, { "finding": "FDA states that neither ipamorelin (free base) nor ipamorelin acetate has a USP or NF drug substance monograph, and that neither is a component of an FDA-approved drug.", "note": "These are the first two of the three statutory doors into 503A compounding; the bulks list is the third, and the advisory committee shut it 0-12-1. FDA also closed the foreign-recognition route: a search of the National Medical Registries, the European Medicines Agency website, and the European, Chinese, Indian and Japanese Pharmacopeias 'did not show any monograph listings for either ipamorelin or ipamorelin acetate'. The one national authority FDA found that HAD acted, acted against it — Australia's Advisory Committee on Medicines Scheduling recommended and confirmed adding ipamorelin to the Poisons Standard under performance and image enhancing drugs, 'for which possession without authority is illegal'.", "source": { "url": "https://www.fda.gov/media/182088/download", "title": "Ipamorelin-Related Bulk Drug Substances (Ipamorelin (free base) and Ipamorelin Acetate) — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, October 29, 2024", "publisher": "FDA", "date": "2024-10-29", "quote": "There is no applicable United States Pharmacopeia (USP) or National Formulary (NF) drug substance monograph for ipamorelin (free base) or its acetate form, and neither is a component of an FDA-approved drug." }, "verifiedAt": "2026-07-16" }, { "finding": "FDA records that clinical development of ipamorelin for postoperative ileus was discontinued because of the Phase 2 trial's results.", "note": "FDA is quoting Ishida et al. 2020, a published review of POI drug development, reporting on the Beck et al. 2014 trial. The reviewers' full statement as FDA reproduces it: 'in patients undergoing bowel resection, ipamorelin did not shorten the time to first meal intake compared with placebo. This phase II clinical trial did not show any significant difference in measurable colonic functions between ipamorelin and placebo. Due to these disappointing results, its development was discontinued.' Read against the marketing, this is the whole record: the only people who ever spent money finding out whether ipamorelin does something in humans stopped when they found out.", "source": { "url": "https://www.fda.gov/media/182088/download", "title": "Ipamorelin-Related Bulk Drug Substances (Ipamorelin (free base) and Ipamorelin Acetate) — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, October 29, 2024", "publisher": "FDA", "date": "2024-10-29", "quote": "Due to these disappointing results, its development was discontinued." }, "verifiedAt": "2026-07-16" }, { "finding": "FDA's overall effectiveness conclusion: evidence is limited for any route, and there are NO data supporting effectiveness by the subcutaneous route that was nominated.", "note": "Two distinct claims in one sentence, and vendors quote neither. 'Limited for any ROA' is the verdict on the intravenous Phase 1 and Phase 2 data that actually exist; 'no data ... for the proposed SC route' is the verdict on the route people are sold. FDA adds that 'professional society guidelines do not discuss use of ipamorelin-related bulk drug substance for GHD or POI' — the specialty bodies that write the standard of care for both evaluated conditions do not mention it at all.", "source": { "url": "https://www.fda.gov/media/182088/download", "title": "Ipamorelin-Related Bulk Drug Substances (Ipamorelin (free base) and Ipamorelin Acetate) — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, October 29, 2024", "publisher": "FDA", "date": "2024-10-29", "quote": "We conclude based on available clinical information that the evidence of effectiveness for GHD or POI is limited for any ROA, and there are no data to support the effectiveness of ipamorelin (free base) or ipamorelin acetate for the proposed SC route of administration for these medical conditions." }, "verifiedAt": "2026-07-16" }, { "finding": "FDA identified, from ipamorelin's ghrelin-receptor mechanism, potential for behavioural reinforcement and addiction and for negative effects on reproductive health and pregnancy — and states the nonclinical studies were too limited to resolve either.", "note": "MAY, not DOES — and FDA says so itself in the same document: 'nonclinical studies were insufficient to demonstrate whether ipamorelin (free base or acetate) has reinforcing and addictive properties', and 'it remains to be determined whether ipamorelin (free base) or ipamorelin acetate ... can negatively impact fertilization and embryofetal development as ghrelin did'. The concern is class-based: in a 2014 mouse study (Luque et al.), researchers reported that systemic treatment with either a ghrelin receptor agonist or a ghrelin receptor antagonist negatively affected fertilization and embryofetal development, and in a 2008 fMRI study (Malik et al.) researchers reported that intravenous ghrelin increased activity in reward-processing brain regions of healthy human subjects during exposure to food images. FDA states outright that at the time of the evaluation it identified NO published nonclinical developmental and reproductive toxicity studies with ipamorelin, and 'did not identify in the publicly available literature nonclinical studies to inform the carcinogenic potential of ipamorelin (free base) or ipamorelin acetate' — for a substance marketed for open-ended anti-aging use. Its closing nonclinical line: 'nonclinical toxicity studies were too limited in scope and duration to inform safety considerations for potential clinical uses'.", "source": { "url": "https://www.fda.gov/media/182088/download", "title": "Ipamorelin-Related Bulk Drug Substances (Ipamorelin (free base) and Ipamorelin Acetate) — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, October 29, 2024", "publisher": "FDA", "date": "2024-10-29", "quote": "From the nonclinical pharmacological perspective, due to its primary mechanism of action as a ghrelin receptor agonist, ipamorelin (free base) or ipamorelin acetate may have behavioral reinforcing properties, which can contribute to development of addiction, and may also negatively affect reproductive health and pregnancy outcomes." }, "verifiedAt": "2026-07-16" }, { "finding": "Ipamorelin is a World Anti-Doping Agency prohibited substance, listed under section S2.4, and FDA records it has been detected in vials confiscated from athletes.", "note": "Recorded because it is the one question about ipamorelin with a hard, checkable, consequential answer, and because the bodybuilding market is a substantial share of the demand FDA describes. FDA cites Cox et al. 2015 for detection of ipamorelin in vials confiscated from athletes in Germany, Belgium and Australia, and states 'in the USA, ipamorelin has been detected in confiscated vials'. Prohibited-list status is an anti-doping sanction matter, not a criminal or FDA one — three separate systems, and a substance can be in trouble under all of them at once.", "source": { "url": "https://www.fda.gov/media/182088/download", "title": "Ipamorelin-Related Bulk Drug Substances (Ipamorelin (free base) and Ipamorelin Acetate) — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, October 29, 2024", "publisher": "FDA", "date": "2024-10-29", "quote": "Ipamorelin is on the list of prohibited substances under section S2.4 of the World Anti-Doping Agency (WADA)." }, "verifiedAt": "2026-07-16" } ], "safetySignals": [ { "signal": "Two deaths occurred among ipamorelin-treated subjects in the Phase 2 postoperative-ileus trial. FDA states it is UNCLEAR whether the deaths were related to ipamorelin.", "note": "THE CAUSALITY CAVEAT IS PART OF THE FINDING, NOT A FOOTNOTE TO IT, AND MUST NEVER BE DROPPED. FDA does not say ipamorelin killed anyone. The two subjects had undergone bowel resection for colon cancer and developed anastomotic leak, a complication reported in about 5% of anastomosis surgeries; FDA records the primary causes of death as hyperkalemia in a subject with aortic clots, sepsis, perforated ulcer, and renal failure and sepsis in a subject with pneumonia. Most SAEs occurred after subjects completed therapy. The population was gravely ill at baseline and both arms had SAEs. Note the tension a careless reader will miss: the Beck 2014 abstract says ipamorelin 'was well tolerated' and does not mention the deaths at all — FDA's reading of the same study is where the fatal SAEs surface. Reading only the abstract, or only FDA's public one-line summary, gives two different and equally incomplete pictures. FDA's public safety-risks page compresses this to 'A study published in literature identified serious adverse events including death when ipamorelin was administered intravenously for improving gastric motility' without naming the study or the causality caveat; the study is Beck et al. 2014. We could not read the Beck full text (paywalled) to confirm FDA's per-arm figures independently.", "source": { "url": "https://www.fda.gov/media/182088/download", "title": "Ipamorelin-Related Bulk Drug Substances (Ipamorelin (free base) and Ipamorelin Acetate) — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, October 29, 2024", "publisher": "FDA", "date": "2024-10-29", "quote": "Although it is unclear whether the deaths reported in the above study were related to ipamorelin, their occurrence in ipamorelin-treated subjects, along with the higher rates of hypokalemia and hyperglycemia reported in ipamorelin-treated subjects, raises safety concerns about the use of ipamorelin in compounding." }, "verifiedAt": "2026-07-16" }, { "signal": "Higher rates of hypokalemia and hyperglycemia in ipamorelin-treated subjects than placebo; reported adverse events also included insomnia, nausea, vomiting and abdominal distention.", "note": "Directionally relevant to how ipamorelin is actually sold. It is marketed for body composition and anti-aging on the strength of growth hormone release, and growth hormone release is exactly the mechanism that drives the glucose signal. FDA makes this explicit as a separate finding: the nomination did not include, and FDA did not identify, sufficient data to conclude that ipamorelin would not present safety concerns similar to those associated with approved products that stimulate GH release, 'such as glucose intolerance and diabetes mellitus'. The absence of a documented harm is not evidence of safety here — it is absence of data.", "source": { "url": "https://www.fda.gov/media/182088/download", "title": "Ipamorelin-Related Bulk Drug Substances (Ipamorelin (free base) and Ipamorelin Acetate) — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, October 29, 2024", "publisher": "FDA", "date": "2024-10-29" }, "verifiedAt": "2026-07-16" }, { "signal": "FDA identified only two FAERS reports for ipamorelin through 2023-09-30, both NON-SERIOUS.", "note": "Recorded to pre-empt the inference vendors draw from it. A thin FAERS file is not a safety record — FAERS is passive surveillance, and a substance sold outside the prescription system by medical spas and research-chemical sellers has almost no reporting pathway into it. One of the two reports involved ipamorelin combined with sermorelin. Ipamorelin is not a component of any FDA-approved drug and has no USP or NF monograph.", "source": { "url": "https://www.fda.gov/media/182088/download", "title": "Ipamorelin-Related Bulk Drug Substances (Ipamorelin (free base) and Ipamorelin Acetate) — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, October 29, 2024", "publisher": "FDA", "date": "2024-10-29" }, "verifiedAt": "2026-07-16" }, { "signal": "FDA identified immunogenicity and characterisation risk: ipamorelin contains unnatural amino acids and may aggregate, and ipamorelin (free base) is not well-characterised.", "note": "This is the finding that keeps ipamorelin acetate in Category 2 under the 503B interim policy to this day, and it is why the 503A withdrawal changed less than the market claims. FDA's stated position on these routes is an information gap, not a clean bill: 'FDA has not identified safety-related information regarding ipamorelin acetate via certain other injectable routes of administration. The agency lacks sufficient information to know whether the drug would cause harm if administered to humans via those routes.' Neither Category status nor a withdrawn nomination is the criminal line: the Watkins indictment (D. Utah, 1:26-cr-00015, 2026-04-01) charges misbranding under 352(b), which is why Category 1 substances sit in the same indictment as BPC-157.", "source": { "url": "https://www.fda.gov/drugs/human-drug-compounding/certain-bulk-drug-substances-use-compounding-may-present-significant-safety-risks", "title": "Certain Bulk Drug Substances for Use in Compounding that May Present Significant Safety Risks", "publisher": "FDA", "date": "2026-04-22", "quote": "Compounded drugs containing Ipamorelin acetate may pose risk for immunogenicity for certain routes of administration due to the potential for aggregation or peptide-related impurities." }, "verifiedAt": "2026-07-16" } ], "faqs": [ { "question": "Is ipamorelin legal in 2026?", "answer": "Ipamorelin is not eligible for use in pharmacy compounding under section 503A. A bulk drug substance qualifies by only three routes — a USP or NF monograph, being a component of an FDA-approved drug, or appearing on FDA's 503A bulks list — and FDA's briefing document states that ipamorelin (free base) and ipamorelin acetate meet none of them: there is no USP or NF monograph for either, neither is a component of an FDA-approved drug, FDA staff proposed not adding either to the bulks list, and the Pharmacy Compounding Advisory Committee voted 0-12-1 against adding each of them on 2024-10-29. Ipamorelin's absence from the 503A list is not permission — the two nominations that could have placed it there were withdrawn by the nominators after that vote — and ipamorelin acetate remains on FDA's list of bulk drug substances that may present significant safety risks. Separately, no list or category status is itself a statement about whether selling or possessing a substance is lawful; ipamorelin is also on the World Anti-Doping Agency prohibited list under section S2.4, and Australia has scheduled it under performance and image enhancing drugs, for which possession without a prescription is illegal there.", "source": { "url": "https://www.fda.gov/media/182088/download", "title": "Ipamorelin-Related Bulk Drug Substances (Ipamorelin (free base) and Ipamorelin Acetate) — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, October 29, 2024", "publisher": "FDA", "date": "2024-10-29" }, "verifiedAt": "2026-07-16" }, { "question": "Did ipamorelin become legal again when FDA removed it from Category 2?", "answer": "No. Ipamorelin acetate has not left FDA's Category 2 — it is still listed among the bulk drug substances FDA has identified as potentially presenting significant safety risks, added under the 503B interim policy on 2023-09-29, and it is the one substance that appears both in FDA's current Category 2 table and in the table of substances whose nominations were withdrawn. What changed is only that the two 503A nominations for ipamorelin were withdrawn by the nominators, and withdrawal moves a substance sideways rather than toward legality: ipamorelin did not enter Category 1, is not on the 503A bulks list, and remains ineligible for compounding under section 503A. For ipamorelin the sequence also matters — FDA's advisory committee had already voted 0 yes, 12 no, 1 abstain against adding both ipamorelin (free base) and ipamorelin acetate to the 503A list on 2024-10-29, so the nominations were not withdrawn from a live process with an open outcome.", "source": { "url": "https://www.fda.gov/drugs/human-drug-compounding/certain-bulk-drug-substances-use-compounding-may-present-significant-safety-risks", "title": "Certain Bulk Drug Substances for Use in Compounding that May Present Significant Safety Risks", "publisher": "FDA", "date": "2026-04-22" }, "verifiedAt": "2026-07-16" }, { "question": "Did FDA approve ipamorelin?", "answer": "No. There is no FDA-approved drug product containing ipamorelin, and FDA's briefing document for the October 29, 2024 Pharmacy Compounding Advisory Committee meeting states that neither ipamorelin (free base) nor ipamorelin acetate is a component of an FDA-approved drug. Ipamorelin was investigated by a pharmaceutical sponsor, Helsinn Therapeutics, in two Phase 2 trials for postoperative ileus and never advanced to Phase 3; no marketing application for it has ever been approved. FDA also found no approval or pharmacopeial recognition abroad — a search of the National Medical Registries, the European Medicines Agency website and the European, Chinese, Indian and Japanese Pharmacopeias returned no monograph listings for ipamorelin or ipamorelin acetate. For both conditions FDA evaluated, approved alternatives already exist: human growth hormone formulations for growth hormone deficiency, and alvimopan, which FDA describes as the only approved drug for accelerating gastrointestinal recovery following bowel resection.", "source": { "url": "https://www.fda.gov/media/182088/download", "title": "Ipamorelin-Related Bulk Drug Substances (Ipamorelin (free base) and Ipamorelin Acetate) — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, October 29, 2024", "publisher": "FDA", "date": "2024-10-29" }, "verifiedAt": "2026-07-16" }, { "question": "Is there any human evidence that ipamorelin works?", "answer": "There is real human data on ipamorelin, and it is negative. Ipamorelin was administered to humans in a Phase 1 study in healthy male volunteers (FDA describes it as 48 subjects), where FDA reports a model showed ipamorelin induced growth hormone release at all dose levels analysed, in a manner dependent on the concentration of ipamorelin — though the lowest-dose group was excluded from that analysis for negligible growth hormone levels — and in a Phase 2 randomised placebo-controlled trial in 114 analysed adults after bowel resection published by Beck et al. in 2014, where researchers reported 'no significant differences between ipamorelin and placebo in the key and secondary efficacy analyses'. A larger Phase 2 trial (NCT01280344, 320 participants) is recorded as completed with no results ever posted or published, and the development programme was then discontinued — FDA quotes a published review stating that, because of the trial's disappointing results, development was discontinued. Both human studies used the intravenous route, not the subcutaneous injection that is sold. FDA states it has not identified data supporting effectiveness of ipamorelin (free base) or ipamorelin acetate for growth hormone deficiency or postoperative ileus — the only two uses FDA evaluated. The uses ipamorelin is actually marketed for, such as weight loss, anti-aging, sleep and bodybuilding, FDA did not evaluate at all, so no FDA finding exists either way on them; searching the published literature ourselves, we found no human efficacy evidence for any of those uses either.", "source": { "url": "https://pubmed.ncbi.nlm.nih.gov/25331030/", "title": "Prospective, randomized, controlled, proof-of-concept study of the Ghrelin mimetic ipamorelin for the management of postoperative ileus in bowel resection patients", "publisher": "PubMed", "date": "2014-10-21", "quote": "There were no significant differences between ipamorelin and placebo in the key and secondary efficacy analyses." }, "verifiedAt": "2026-07-16" }, { "question": "Is ipamorelin safe?", "answer": "Nobody knows, and FDA has documented specific reasons for concern rather than reassurance. In the Phase 2 postoperative-ileus trial, two deaths occurred among ipamorelin-treated subjects; FDA states it is unclear whether those deaths were related to ipamorelin — the subjects had undergone bowel resection for colon cancer and developed anastomotic leak — but FDA concluded that their occurrence in ipamorelin-treated subjects, together with higher rates of hypokalemia and hyperglycemia in ipamorelin-treated subjects, 'raises safety concerns about the use of ipamorelin in compounding'. FDA further identified, from ipamorelin's ghrelin-receptor mechanism, potential for behavioural reinforcement and addiction and for negative effects on reproductive health and pregnancy outcomes, and stated that the nonclinical studies were too limited in scope and duration to resolve either; it identified no published developmental and reproductive toxicity studies and no studies informing carcinogenic potential for a substance marketed for open-ended use. FDA also flagged immunogenicity risk from potential aggregation and peptide-related impurities. FDA found only two adverse-event reports for ipamorelin in its FAERS database through 2023-09-30, both non-serious, but FAERS is passive surveillance and a substance sold outside the prescription system has almost no reporting pathway into it — a thin file is absence of data, not evidence of safety.", "source": { "url": "https://www.fda.gov/media/182088/download", "title": "Ipamorelin-Related Bulk Drug Substances (Ipamorelin (free base) and Ipamorelin Acetate) — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, October 29, 2024", "publisher": "FDA", "date": "2024-10-29" }, "verifiedAt": "2026-07-16" }, { "question": "Will ipamorelin make me fail a drug test?", "answer": "Ipamorelin is a prohibited substance in sport. FDA's briefing document states that ipamorelin is on the World Anti-Doping Agency's prohibited list under section S2.4, which means it is banned for athletes competing under a WADA-compliant anti-doping programme. FDA also records that ipamorelin has been detected in vials confiscated from athletes in Germany, Belgium and Australia, and in confiscated vials in the United States. Whether any given laboratory screen detects it depends on the panel used, and standard employment or clinical drug screens are not anti-doping panels; prohibited-list status is an anti-doping matter and is separate from FDA's compounding determinations and from criminal law.", "source": { "url": "https://www.fda.gov/media/182088/download", "title": "Ipamorelin-Related Bulk Drug Substances (Ipamorelin (free base) and Ipamorelin Acetate) — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, October 29, 2024", "publisher": "FDA", "date": "2024-10-29", "quote": "Ipamorelin is on the list of prohibited substances under section S2.4 of the World Anti-Doping Agency (WADA)." }, "verifiedAt": "2026-07-16" } ] }, { "slug": "kisspeptin-10", "name": "Kisspeptin-10", "aliases": [ "KP-10", "Kisspeptin-112-121", "Metastin 45-54", "KISS1 (112-121)" ], "url": "https://peptides101.com/compounds/kisspeptin-10", "moleculeNote": "The C-terminal decapeptide of the KISS1 gene product, and the shortest fragment retaining full agonist activity at the kisspeptin receptor (KISS1R/GPR54). It is one of several endogenous kisspeptin isoforms; kisspeptin-54 (metastin) is a distinct, longer isoform. THE ISOFORM IS LOAD-BEARING, in the same way full-length Tβ4 versus the 17-23 fragment is load-bearing for TB-500. The human studies most often invoked to sell kisspeptin-10 — the randomised trial in men with hypoactive sexual desire disorder and the sexual-brain-processing fMRI work (Comninos, Abbara and colleagues at Imperial College London) — administered KISSPEPTIN-54, not kisspeptin-10. Verified 2026-07-16. Only FDA's Category 2 listing and the gonadotrophin studies below are scoped to kisspeptin-10 itself.", "quickAnswer": "Kisspeptin-10 is in FDA's 503A Category 2 — bulk drug substances that raise significant safety risks — on the list updated 2026-05-14, FDA's Pharmacy Compounding Advisory Committee voted 0-11 against adding kisspeptin-10 to the 503A bulks list on 2024-10-29, and FDA has recorded that there is no approved product in any country containing kisspeptin-10. Kisspeptin-10 has genuinely been administered to humans — FDA counted approximately 300 subjects across small studies, a figure FDA flagged may be an overestimate, so this is not a compound with zero human exposure — but that exposure is essentially all intravenous: FDA found no study administering kisspeptin-10 to humans intramuscularly and a single subcutaneous study, in healthy women, that did not report safety outcomes, while intramuscular and subcutaneous are the routes kisspeptin-10 was nominated for. FDA's own conclusion is that “there is insufficient evidence to make a conclusion on the effectiveness of kisspeptin-10 as a treatment option for men with secondary hypogonadism.”", "fdaStatus": { "value": "not-approved", "note": "Not an FDA-approved drug for any indication, and not in active development toward approval. That says nothing about whether it is sold — it is.", "source": { "url": "https://www.fda.gov/media/94155/download", "title": "Bulk Drug Substances Nominated for Use in Compounding Under Section 503A of the Federal Food, Drug, and Cosmetic Act", "publisher": "FDA", "date": "2026-05-14", "quote": "503A Category 2: Bulk Drug Substances that Raise Significant Safety Risks" }, "verifiedAt": "2026-07-16" }, "compoundingStatus": { "value": "category-2", "note": "Verified by fetching and text-extracting the list updated 2026-05-14 directly. Kisspeptin-10 is one of exactly six substances in Category 2 — with Cesium Chloride, Domperidone, Germanium Sesquioxide, Ibutamoren Mesylate, and Quinacrine Hydrochloride for intrauterine administration. This is the atypical case in this library: it did NOT leave Category 2 by withdrawal the way BPC-157, TB-500, epitalon, semax, MOTS-c, KPV and DSIP did. It is still listed, under the heading naming significant safety risks, and it is not on the 503A bulks list. Category 2 is nevertheless not the criminal line either: the Watkins indictment (D. Utah, 1:26-cr-00015, 2026-04-01) charges misbranding under 352(b), which is why Category 1 substances sit in the same indictment as substances that were never listed at all. Sourcing and labeling are the line.", "source": { "url": "https://www.fda.gov/media/94155/download", "title": "Bulk Drug Substances Nominated for Use in Compounding Under Section 503A of the Federal Food, Drug, and Cosmetic Act", "publisher": "FDA", "date": "2026-05-14", "quote": "503A Category 2: Bulk Drug Substances that Raise Significant Safety Risks" }, "verifiedAt": "2026-07-16" }, "evidence": { "tier": "promising-but-unproven", "humanAdministrationChecked": true, "note": "Administration check run per study, not inferred from counts. In a 2011 study, George, Veldhuis, Roseweir and colleagues administered kisspeptin-10 to six healthy men as ascending intravenous boluses against a saline vehicle. CORRECTION, 2026-07-16: this note previously said the dose order was 'randomised and blinded'. The paper says the opposite on the first half — 'Doses were administered in increasing order for safety reasons and visits were at least 1 wk apart' — and the blinding it reports is of participants only: 'Participants were blinded to the dose of kisspeptin-10.' The researchers reported a rise in serum LH that did NOT increase monotonically with dose, and the authors' finding at the top of the range is stronger than this note previously allowed: 'There was, however, no significant increase in LH concentration after the highest dose administered …, and the mean LH after this dose was significantly less than after the …' two lower doses it names. Not merely a reduced response at the top dose — no significant increase over vehicle at all. In a 2015 single-blinded, placebo-controlled study, Jayasena and colleagues infused kisspeptin-10 intravenously into healthy men and reported gonadotrophin secretion similar to kisspeptin-54 but lower than GnRH. Both papers were opened and both ADMINISTERED the compound — this is real human exposure data, unlike MOTS-c or TB-500. CORRECTION, 2026-07-16: this note previously said the exposure was confined to 'single-digit cohorts of healthy male volunteers'. That understated it. FDA's 2024 PCAC briefing document counts approximately 300 subjects across the published studies, including men and women with idiopathic hypogonadotropic hypogonadism, men with type 2 diabetes and low testosterone, women with hyperprolactinemia, and adolescents with delayed puberty — patients, not only healthy volunteers. See fdaFindings. The tier stops at promising-but-unproven anyway, and for the reason FDA gives rather than the one this note originally gave: the endpoints are PHARMACODYNAMIC (serum LH, FSH, testosterone) and the studies are, in FDA's word, exploratory. Limitations, per the authors: n=6 and n=4 respectively for the 2011 dose-response and infusion arms; n=5 per group in 2015; healthy volunteers rather than patients; and the 2011 authors could not measure serum kisspeptin-10 concentrations owing to suboptimal sample processing. No adequate, well-controlled trial reports a clinical outcome for kisspeptin-10 in any patient population, and moving a hormone in healthy volunteers is not a demonstration that a treatment works.", "source": { "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC3380939/", "title": "Kisspeptin-10 Is a Potent Stimulator of LH and Increases Pulse Frequency in Men", "publisher": "Journal of Clinical Endocrinology & Metabolism (via PubMed Central)", "date": "2011-06-01" }, "verifiedAt": "2026-07-16" }, "fdaApproval": null, "fdaFindings": [ { "finding": "FDA placed Kisspeptin-10 in 503A Category 2 — bulk drug substances that raise significant safety risks — on 2023-09-29, and it remains listed there as of the list updated 2026-05-14.", "note": "Note what FDA's finding is and is not. It is not a finding that kisspeptin-10 was shown to harm anyone; it is a finding that FDA cannot tell, and that the manufacturing and characterisation problems are real. FDA's own next sentence is explicit: it has 'no, or only limited, safety-related information for the proposed routes of administration' and 'lacks sufficient information to know whether the drug would cause harm when administered to humans.' An evidentiary vacuum, recorded as a risk — not a loophole.", "source": { "url": "https://www.fda.gov/drugs/human-drug-compounding/certain-bulk-drug-substances-use-compounding-may-present-significant-safety-risks", "title": "Certain Bulk Drug Substances for Use in Compounding that May Present Significant Safety Risks", "publisher": "FDA", "date": "2023-09-29", "quote": "Compounded drugs containing Kisspeptin-10 may pose risk for immunogenicity for certain routes of administration and may have complexities with regard to peptide-related impurities and API characterization." }, "verifiedAt": "2026-07-16" }, { "finding": "The Category 2 safety risks FDA identified for Kisspeptin-10 are scoped to the 503A compounding pathway only; FDA lists no 503B date for the substance.", "note": "Recorded because the table distinguishes 503A from 503B per substance — ipamorelin acetate, the row directly above it, carries a 503B date alone, and ibutamoren mesylate carries both ('503A; 503B'). Kisspeptin-10's row reads 503A alone. CORRECTION, 2026-07-16: this note previously named ibutamoren mesylate as the row directly above and as the 503B-only comparator; it is two rows up and it carries both, which collapsed the intended contrast. The claim the note exists for — that kisspeptin-10's row reads 503A alone — is unaffected and verified against the list.", "source": { "url": "https://www.fda.gov/drugs/human-drug-compounding/certain-bulk-drug-substances-use-compounding-may-present-significant-safety-risks", "title": "Certain Bulk Drug Substances for Use in Compounding that May Present Significant Safety Risks", "publisher": "FDA", "date": "2023-09-29" }, "verifiedAt": "2026-07-16" }, { "finding": "FDA proposed not adding kisspeptin-10 to the 503A bulks list, and on 2024-10-29 its Pharmacy Compounding Advisory Committee voted 0 yes, 11 no, 0 abstain against placing kisspeptin-10 on that list.", "note": "This is the finding the previous revision of this record denied existed. Read the vote precisely. It is not 11 people disliking a peptide: the question put to the committee was FDA's own proposal, the nominator (Farmakeio/Evexias) was invited to present and did, two temporary voting members were seated for the kisspeptin-10 topic alone (Joseph P. Alukal, MD; Roger R. Dmochowski, MD), and the result was still unanimous. Compare the same day's other votes, which were NOT unanimous — L-theanine 1-12, ibutamoren mesylate 1-13, ipamorelin 0-12-1. Kisspeptin-10 drew the only clean sweep of the four substances heard. Note also what a PCAC vote is not: it is advisory, and as of the bulks list updated 2026-05-14 no final rule under 21 CFR 216.23 has issued for kisspeptin-10 either way — the substance sits in Category 2, still, not on a final not-included list.", "source": { "url": "https://www.fda.gov/media/185412/download", "title": "Final Summary Minutes of the Pharmacy Compounding Advisory Committee Meeting, October 29, 2024", "publisher": "FDA", "date": "2024-10-29", "quote": "VOTE: FDA is proposing that Kisspeptin-10 NOT be included on the 503A Bulks List. Should Kisspeptin-10 be placed on the list? Vote Result: Yes: 0 No: 11 Abstain: 0 … The committee unanimously agreed that Kisspeptin-10 should not be included on the 503A Bulks List due to the lack of convincing safety and efficacy data." }, "verifiedAt": "2026-07-16" }, { "finding": "FDA's stated basis for proposing not to add kisspeptin-10 was four-fold: poor physicochemical characterization, absent immunogenicity information, insufficient effectiveness evidence, and the existence of approved alternatives for the proposed indication.", "note": "The fourth limb is the one that never appears on a vendor page and is the most decision-relevant of the four. FDA is not saying nothing works for this condition — it is saying something already does: 'there are FDA-approved drug products that are indicated to treat secondary hypogonadism, a potentially serious condition.' The compounding question is therefore not 'is kisspeptin-10 better than nothing' but 'is an uncharacterised bulk substance better than an approved product for a serious condition', which is a materially harder question and the one FDA actually answered.", "source": { "url": "https://www.fda.gov/media/182089/download", "title": "FDA Briefing Document — Pharmacy Compounding Advisory Committee Meeting, October 29, 2024 (Kisspeptin-10, evaluated for the treatment of secondary hypogonadism in men)", "publisher": "FDA", "date": "2024-10-29", "quote": "On balance, the physicochemical characterization, information on historical use, evidence of effectiveness, and safety information identified for kisspeptin-10 weigh against inclusion of this substance on the 503A Bulks List. In particular, FDA's proposal regarding this substance is based on the fact that kisspeptin-10 is not well characterized from a physicochemical perspective, there is a lack of information on immunogenicity risks, there is insufficient evidence to make a conclusion on the effectiveness of kisspeptin-10 as a treatment option for men with secondary hypogonadism, and there are FDA-approved drug products that are indicated to treat secondary hypogonadism, a potentially serious condition. Accordingly, we propose not adding kisspeptin-10 to the 503A Bulks List." }, "verifiedAt": "2026-07-16" }, { "finding": "FDA recorded that no product containing kisspeptin-10 is approved anywhere in the world, and that kisspeptin-10 does not appear in the European or Japanese Pharmacopeias.", "note": "Worth having in this exact form because the usual deflection is jurisdictional — 'it's approved in Europe / Japan / somewhere.' FDA closed that door in one sentence, and it closed the compendial door in the same sentence. The pharmacopeia half is not decoration: under section 503A a bulk substance that is the subject of an applicable USP or NF monograph can be compounded WITHOUT appearing on the bulks list, so the absence of a monograph is precisely why the bulks-list question is dispositive here.", "source": { "url": "https://www.fda.gov/media/182089/download", "title": "FDA Briefing Document — Pharmacy Compounding Advisory Committee Meeting, October 29, 2024 (Kisspeptin-10, evaluated for the treatment of secondary hypogonadism in men)", "publisher": "FDA", "date": "2024-10-29", "quote": "There is no approved product in any country containing kisspeptin-10 at this time, nor is kisspeptin-10 found in the European or Japanese Pharmacopeias." }, "verifiedAt": "2026-07-16" }, { "finding": "FDA identified several small studies that administered kisspeptin-10 to humans, totalling approximately 300 subjects across intravenous and subcutaneous routes — and flagged that figure as possibly an overestimate. That exposure is essentially all intravenous: FDA found no human study by the intramuscular route, and a single subcutaneous study, in approximately 35 healthy women, that reported no safety outcomes.", "note": "Recorded as an explicit POSITIVE, and it is the finding that separates this record from the house pattern. FDA's characteristic sentence for the peptides in this library is 'we have not identified any human exposure data'. It did not write that here, because it could not. Per FDA's own count kisspeptin-10 has been given to roughly 300 people, including men and women with idiopathic hypogonadotropic hypogonadism, men with type 2 diabetes and low testosterone, women with hyperprolactinemia, and adolescents with delayed puberty — so the exposure extends beyond healthy volunteers, which corrects this record's earlier evidence note. Anyone citing this site for 'no human data on kisspeptin-10' is citing it wrongly. What FDA concluded from those 300 is the next finding, and it is the part that matters.", "source": { "url": "https://www.fda.gov/media/182089/download", "title": "FDA Briefing Document — Pharmacy Compounding Advisory Committee Meeting, October 29, 2024 (Kisspeptin-10, evaluated for the treatment of secondary hypogonadism in men)", "publisher": "FDA", "date": "2024-10-29", "quote": "We identified several small studies that administered kisspeptin-10 to humans. … Based on these studies, kisspeptin-10 has been administered via the IV and SC ROA to approximately 300 subjects … This may be an overestimate as it is unclear if there is overlap in subjects between the studies. … Kisspeptin-10 was nominated for SC and IM administration. We found no studies that administered kisspeptin-10 to humans via the IM ROA. We identified a single study that administered a single SC bolus of kisspeptin-10 to approximately 35 healthy women. Safety outcomes were not reported in this study." }, "verifiedAt": "2026-07-16" }, { "finding": "FDA concluded that there is insufficient evidence to reach a conclusion on the effectiveness of kisspeptin-10 for secondary hypogonadism in men — the only use it evaluated — and that no study administered kisspeptin-10 by the proposed routes in men with hypogonadism.", "note": "The single most citable sentence available about this compound, and the one that resolves the apparent contradiction with the finding above. Roughly 300 people received it; FDA read the whole set and still could not get to an effectiveness conclusion. 'Exploratory' is the operative word — these were mechanism studies, not treatment trials. And note the route gap, which is the sharpest fact on this page: every human study FDA found used the intravenous route (plus one subcutaneous study in healthy women), while the NOMINATED routes were intramuscular and subcutaneous. FDA found no study at all administering kisspeptin-10 intramuscularly to humans. Kisspeptin-10 sold for self-injection is therefore being used by a route for which the human literature FDA assembled is essentially empty — the published infusions do not transfer to it.", "source": { "url": "https://www.fda.gov/media/182089/download", "title": "FDA Briefing Document — Pharmacy Compounding Advisory Committee Meeting, October 29, 2024 (Kisspeptin-10, evaluated for the treatment of secondary hypogonadism in men)", "publisher": "FDA", "date": "2024-10-29", "quote": "There is insufficient evidence to make a conclusion on the effectiveness of kisspeptin-10 as a treatment option for men with secondary hypogonadism. It is not possible to draw any meaningful conclusions on effectiveness from the studies identified in this evaluation due to the small number of subjects included, the exploratory nature of the studies, and the dosing of kisspeptin-10 (ROA and frequency of administration) used in the studies. We are not aware of studies that administered kisspeptin-10 via the proposed routes of administration (IM or SC) in men with hypogonadism. In addition, it is unclear if chronic IV administration of kisspeptin-10 would confer any clinical benefit in this patient population." }, "verifiedAt": "2026-07-16" }, { "finding": "FDA found kisspeptin-10 is not well characterized from a physical and chemical perspective, because impurity data for it were absent both from the published literature and from the certificate of analysis supplied with the nomination.", "note": "This is a finding about the PAPERWORK, and that is what makes it damning rather than pedantic. The certificate of analysis is the document a seller points to when asked to prove what is in the vial. FDA looked at the CoA the nominator itself chose to submit in support of its own nomination, and found it did not establish the impurity profile. A CoA from a research-peptide vendor is not a stronger document than the one FDA rejected here.", "source": { "url": "https://www.fda.gov/media/182089/download", "title": "FDA Briefing Document — Pharmacy Compounding Advisory Committee Meeting, October 29, 2024 (Kisspeptin-10, evaluated for the treatment of secondary hypogonadism in men)", "publisher": "FDA", "date": "2024-10-29", "quote": "the nominated BDS, kisspeptin-10, is not well characterized from the physical and chemical characterization perspective because certain critical characterization data specific to kisspeptin-10, such as likely impurities, were neither found in the publicly available scientific literature nor they were provided in the CoA, which are offered as evidence to establishing identity, purity, and impurity profiles of kisspeptin-10." }, "verifiedAt": "2026-07-16" }, { "finding": "FDA's interim policy extends its stated enforcement forbearance only to 503A Category 1 substances; substances placed in Category 2 are expressly outside it.", "note": "Recorded because it is the sentence that converts a category label into a consequence, and this record would be decorative without it. The Category 1 policy is a promise not to act: FDA 'does not intend to take action against a State-licensed pharmacy, Federal facility, or licensed physician' compounding with such a substance, subject to four conditions — the first of which is literally that 'the bulk drug substance appears in 503A Category 1 on FDA's website.' Kisspeptin-10 fails condition one. The guidance also states the baseline that then applies: a drug product compounded from a bulk substance that is neither on the 503A bulks list, nor the subject of an applicable USP or NF monograph, nor a component of an FDA-approved drug 'is not eligible for the exemptions in section 503A and may violate the FD&C Act.' None of the three is true of kisspeptin-10. Read this against the WITHDRAWN compounds in this library, where the market's inference runs the other way: withdrawal removes a substance from the categories and therefore from the Category 1 forbearance too, so leaving the list moves a compound sideways or backwards, never toward legality.", "source": { "url": "https://www.fda.gov/media/174456/download", "title": "Interim Policy on Compounding Using Bulk Drug Substances Under Section 503A of the Federal Food, Drug, and Cosmetic Act — Guidance for Industry", "publisher": "FDA", "date": "2025-01-07", "quote": "503A Category 2 – Substances Nominated for the Bulks List That Raise Significant Safety Risks: These substances were nominated with sufficient supporting information to permit FDA to evaluate them, and they may be eligible for inclusion on the 503A bulks list. However, FDA has identified significant safety risks relating to the use of these substances in compounding pending further evaluation and, therefore, does not intend to adopt the policy described for the substances in Category 1." }, "verifiedAt": "2026-07-16" } ], "safetySignals": [ { "signal": "FDA identified immunogenicity risk for certain routes of administration, plus complexities in peptide-related impurities and active pharmaceutical ingredient characterization.", "note": "This is the same immunogenicity-plus-characterisation language FDA applies to BPC-157 and other peptides, and it is a statement about the SUBSTANCE AS COMPOUNDED — impurity profile and API identity — not about the molecule as studied under IND in the published infusion work. What arrives from a research-peptide vendor is not what was infused in those studies, and FDA's finding is squarely about the former.", "source": { "url": "https://www.fda.gov/drugs/human-drug-compounding/certain-bulk-drug-substances-use-compounding-may-present-significant-safety-risks", "title": "Certain Bulk Drug Substances for Use in Compounding that May Present Significant Safety Risks", "publisher": "FDA", "date": "2023-09-29", "quote": "FDA has no, or only limited, safety-related information for the proposed routes of administration. Therefore, the agency lacks sufficient information to know whether the drug would cause harm when administered to humans." }, "verifiedAt": "2026-07-16" }, { "signal": "No adverse-event signal specific to kisspeptin-10 was identified in the FDA Category 2 summary; the listed basis is absence of safety information rather than observed harm.", "note": "Recorded as an explicit negative so the gap is visible rather than silently absent. Contrast the neighbouring Category 2 entries, where FDA does cite observed harm: ibutamoren mesylate carries a trial 'terminated early due to a potential safety signal of congestive heart failure'. Kisspeptin-10's entry carries no equivalent. CORRECTION, 2026-07-16: this note previously continued 'FDA has not published a PCAC briefing document for kisspeptin-10 … so no FAERS review of the kind available for BPC-157 exists for this compound.' Both halves were false. FDA published a 64-page briefing document for the 2024-10-29 PCAC meeting, and it contains a full FAERS review. The error was inferring absence-from-the-2026-docket to absence-from-the-record; the kisspeptin-10 evaluation simply happened in 2024. See the FAERS finding below.", "source": { "url": "https://www.fda.gov/drugs/human-drug-compounding/certain-bulk-drug-substances-use-compounding-may-present-significant-safety-risks", "title": "Certain Bulk Drug Substances for Use in Compounding that May Present Significant Safety Risks", "publisher": "FDA", "date": "2023-09-29" }, "verifiedAt": "2026-07-16" }, { "signal": "A search of FAERS through 2023-10-25 retrieved exactly one adverse-event report for kisspeptin-10, and a search of CAERS retrieved zero.", "note": "One report is not a clean safety record and must not be read as one — FDA says so itself in the same passage, noting it 'does not receive all adverse event reports that may potentially occur with a product, especially for compounded products.' A compound sold outside the prescribing system generates almost no reports precisely BECAUSE it is sold outside the system: there is no prescriber to file. The single report concerned a 17-year-old male with hypogonadotropic hypogonadism given a compounded injectable kisspeptin-10 product (Tailor Made Compounding) subcutaneously over roughly six weeks to stimulate testosterone production; the reported outcome was weight gain and increased estrone — 'which were not the desired effects' — and FDA notes the case is limited by unclear temporal relationship and insufficient information. FDA's separate safety conclusion is the one to quote: 'Based on available data, there is a lack of information about whether kisspeptin-10 can be safely used in the intended population, the appropriate dose range, and frequency and duration of dosing for the proposed routes of administration.' Note that FDA reported no reported compounded drug products containing kisspeptin-10 in its outsourcing-facility product reporting data from January 2017 to June 2023 — the 503B channel was not making this, which is consistent with kisspeptin-10's row on the Category 2 table reading 503A alone.", "source": { "url": "https://www.fda.gov/media/182089/download", "title": "FDA Briefing Document — Pharmacy Compounding Advisory Committee Meeting, October 29, 2024 (Kisspeptin-10, evaluated for the treatment of secondary hypogonadism in men)", "publisher": "FDA", "date": "2024-10-29", "quote": "The Office of Surveillance and Epidemiology conducted a search of the FAERS database for reports of adverse events (AEs) for kisspeptin-10 through October 25, 2023. The search retrieved one report … Considering these limitations, FDA cannot make definitive conclusions regarding the safety of kisspeptin-10 based on FAERS data alone." }, "verifiedAt": "2026-07-16" } ], "faqs": [ { "question": "Is kisspeptin-10 legal in 2026?", "answer": "No — kisspeptin-10 has no lawful route into pharmacy compounding in the United States as of July 2026, and a product compounded with it may violate federal law. Kisspeptin-10 is not on FDA's 503A bulks list, is not the subject of a USP or NF monograph, and is not a component of any FDA-approved drug product, and FDA's guidance states that a drug product compounded from a bulk drug substance meeting none of those three conditions “is not eligible for the exemptions in section 503A and may violate the FD&C Act.” FDA's interim enforcement policy — under which it says it does not intend to take action against a State-licensed pharmacy, Federal facility, or licensed physician compounding with a nominated substance — requires that the substance appear in 503A Category 1. Kisspeptin-10 is in 503A Category 2, which FDA describes as substances that raise significant safety risks and for which it “does not intend to adopt the policy described for the substances in Category 1.”", "source": { "url": "https://www.fda.gov/media/174456/download", "title": "Interim Policy on Compounding Using Bulk Drug Substances Under Section 503A of the Federal Food, Drug, and Cosmetic Act — Guidance for Industry", "publisher": "FDA", "date": "2025-01-07", "quote": "A drug product compounded from a bulk drug substance that does not meet any of these three conditions is not eligible for the exemptions in section 503A and may violate the FD&C Act." }, "verifiedAt": "2026-07-16" }, { "question": "Did kisspeptin-10 become legal when FDA removed it from Category 2?", "answer": "FDA has not removed kisspeptin-10 from Category 2 — the premise is false. Kisspeptin-10 is one of exactly six substances still listed in 503A Category 2 on FDA's bulk drug substances list updated 2026-05-14, alongside cesium chloride, domperidone, germanium sesquioxide, ibutamoren mesylate, and quinacrine hydrochloride for intrauterine administration. Kisspeptin-10 is frequently confused with the peptides whose nominations were withdrawn by their nominators — BPC-157, TB-500, epitalon, semax, MOTS-c, KPV and DSIP among them — but kisspeptin-10 is not one of them and remains listed under the heading naming significant safety risks. Withdrawal would not have made kisspeptin-10 legal in any event: leaving the categories also removes a substance from the Category 1 enforcement policy, which is the only forbearance FDA's interim guidance offers.", "source": { "url": "https://www.fda.gov/media/94155/download", "title": "Bulk Drug Substances Nominated for Use in Compounding Under Section 503A of the Federal Food, Drug, and Cosmetic Act", "publisher": "FDA", "date": "2026-05-14", "quote": "503A Category 2: Bulk Drug Substances that Raise Significant Safety Risks … Cesium Chloride … Domperidone … Germanium Sesquioxide … Ibutamoren Mesylate … Kisspeptin-10 … Quinacrine Hydrochloride for intrauterine administration" }, "verifiedAt": "2026-07-16" }, { "question": "Did FDA approve kisspeptin-10?", "answer": "No. FDA has not approved kisspeptin-10 for any indication, and in its briefing document for the 2024-10-29 Pharmacy Compounding Advisory Committee meeting FDA stated that “there is no approved product in any country containing kisspeptin-10 at this time, nor is kisspeptin-10 found in the European or Japanese Pharmacopeias.” The only regulatory question FDA has evaluated for kisspeptin-10 is a narrower one — whether it may be used as a bulk drug substance in pharmacy compounding under section 503A — and FDA proposed not adding it to that list.", "source": { "url": "https://www.fda.gov/media/182089/download", "title": "FDA Briefing Document — Pharmacy Compounding Advisory Committee Meeting, October 29, 2024 (Kisspeptin-10, evaluated for the treatment of secondary hypogonadism in men)", "publisher": "FDA", "date": "2024-10-29", "quote": "There is no approved product in any country containing kisspeptin-10 at this time, nor is kisspeptin-10 found in the European or Japanese Pharmacopeias." }, "verifiedAt": "2026-07-16" }, { "question": "Is there any human evidence that kisspeptin-10 works?", "answer": "Kisspeptin-10 has been administered to humans — FDA identified several small studies totalling approximately 300 subjects, a figure FDA flagged may be an overestimate because subjects may overlap between studies, so unlike many peptides sold alongside it, kisspeptin-10 is not a compound with zero human exposure data. That exposure is essentially all intravenous, though: FDA found no study that administered kisspeptin-10 to humans intramuscularly, and a single subcutaneous study, a one-off bolus in about 35 healthy women, in which safety outcomes were not reported — and subcutaneous and intramuscular are the routes kisspeptin-10 was nominated for and is sold for self-injection. But it has not been shown to work. Having reviewed those studies, FDA concluded that “there is insufficient evidence to make a conclusion on the effectiveness of kisspeptin-10 as a treatment option for men with secondary hypogonadism,” and that it was “not possible to draw any meaningful conclusions on effectiveness from the studies identified in this evaluation due to the small number of subjects included, the exploratory nature of the studies,” and the routes and frequencies used. In the published human work FDA reviewed, the measured endpoints are short-term hormone responses such as serum luteinising hormone, not clinical outcomes — and FDA reported that even the hormone response does not carry through to the thing men would be taking it for: “transient rises in LH response to acute kisspeptin-10 administration are not associated with sustained increases in testosterone. Thus, even if kisspeptin-10 induces an LH response in men, it is unclear if there are corresponding increases in testosterone levels.”", "source": { "url": "https://www.fda.gov/media/182089/download", "title": "FDA Briefing Document — Pharmacy Compounding Advisory Committee Meeting, October 29, 2024 (Kisspeptin-10, evaluated for the treatment of secondary hypogonadism in men)", "publisher": "FDA", "date": "2024-10-29", "quote": "There is insufficient evidence to make a conclusion on the effectiveness of kisspeptin-10 as a treatment option for men with secondary hypogonadism. … Additionally, George et al. (2013) notes that transient rises in LH response to acute kisspeptin-10 administration are not associated with sustained increases in testosterone. Thus, even if kisspeptin-10 induces an LH response in men, it is unclear if there are corresponding increases in testosterone levels." }, "verifiedAt": "2026-07-16" }, { "question": "What did FDA's advisory committee decide about kisspeptin-10?", "answer": "FDA's Pharmacy Compounding Advisory Committee voted unanimously against kisspeptin-10 on 2024-10-29 — 0 yes, 11 no, 0 abstain — on the question of whether kisspeptin-10 should be placed on the 503A bulks list. The committee's recorded reason was “the lack of convincing safety and efficacy data,” and the use FDA had evaluated was the treatment of secondary hypogonadism in men. The nominator was invited to present in support of the nomination and did so, and the vote was still unanimous; of the four bulk drug substances the committee heard that day, kisspeptin-10 was the only one to draw a unanimous vote. A PCAC vote is advisory, and as of FDA's bulks list updated 2026-05-14 kisspeptin-10 remains in 503A Category 2 pending a final rule.", "source": { "url": "https://www.fda.gov/media/185412/download", "title": "Final Summary Minutes of the Pharmacy Compounding Advisory Committee Meeting, October 29, 2024", "publisher": "FDA", "date": "2024-10-29", "quote": "VOTE: FDA is proposing that Kisspeptin-10 NOT be included on the 503A Bulks List. Should Kisspeptin-10 be placed on the list? Vote Result: Yes: 0 No: 11 Abstain: 0 … The committee unanimously agreed that Kisspeptin-10 should not be included on the 503A Bulks List due to the lack of convincing safety and efficacy data." }, "verifiedAt": "2026-07-16" } ] }, { "slug": "kpv", "name": "KPV", "aliases": [ "lysine-proline-valine", "Lys-Pro-Val", "α-MSH(11-13)", "alpha-MSH (11-13)", "KPV acetate" ], "url": "https://peptides101.com/compounds/kpv", "moleculeNote": "A tripeptide of lysine (K), proline (P) and valine (V), corresponding to the C-terminal tripeptide of α-melanocyte-stimulating hormone. FDA evaluates two distinct substances: KPV (free base) and KPV acetate — different active pharmaceutical ingredients, and hence different bulk drug substances. The distinction is not academic: the sole nomination was internally inconsistent about which one it meant (the certificate of analysis named one substance in its title and a different one by molecular formula), and FDA could not tell which was intended. The 'α-MSH fragment' framing carries an implication FDA's own review rejects — see the mechanism finding below.", "quickAnswer": "KPV is not on the FDA 503A Bulks List and cannot lawfully be used as a bulk drug substance in compounded drug products; the only nomination for it was withdrawn, which moved it no closer to the list, and FDA staff proposed not adding KPV (free base) or KPV acetate ahead of the Pharmacy Compounding Advisory Committee meeting on 23-24 July 2026. FDA states that the nomination did not include, and that FDA has not identified, any clinical studies or human exposure data for KPV via any route of administration.", "fdaStatus": { "value": "not-approved", "note": "Not an FDA-approved drug for any indication, and not in active development toward approval. That says nothing about whether it is sold — it is.", "source": { "url": "https://www.fda.gov/media/193346/download", "title": "KPV-Related Bulk Drug Substances — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, July 23-24, 2026", "publisher": "FDA", "date": "2026-07-23" }, "verifiedAt": "2026-07-16" }, "compoundingStatus": { "value": "withdrawn-from-nomination", "note": "Absent from Categories 1, 2 and 3 in the list updated 2026-05-14 — verified by fetching and text-extracting the document directly. Category 2 contains exactly six substances (Cesium Chloride, Domperidone, Germanium Sesquioxide, Ibutamoren Mesylate, Kisspeptin-10, Quinacrine HCl for intrauterine administration); KPV is not among them and appears nowhere in the document. The single nomination — from Wells Pharmacy Network, Document ID FDA-2015-N-3534-0294 — was withdrawn (withdrawal at FDA-2015-N-3534-0484). Withdrawal is not a legalisation event: KPV is not on the 503A bulks list and remains non-compoundable. One detail distinguishes KPV from most of this cohort and cuts AGAINST the 'FDA dropped it, access is coming' reading — FDA did not drop it. The briefing document states the nomination was withdrawn 'and FDA is evaluating the substances at its discretion', on its own initiative, expressly because of its safety concerns. FDA carried the evaluation forward after the nominator walked away.", "source": { "url": "https://www.fda.gov/media/193346/download", "title": "KPV-Related Bulk Drug Substances — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, July 23-24, 2026", "publisher": "FDA", "date": "2026-07-23" }, "verifiedAt": "2026-07-16" }, "evidence": { "tier": "animal-or-in-vitro-only", "humanAdministrationChecked": true, "note": "Zero human administration, and unusually well-evidenced as zero. The administration check did not rest on trial counts. FDA ran the check itself across PubMed, Embase, ClinicalTrials.gov, DailyMed and Drugs@FDA and reported that its search 'did not identify data, such as clinical studies, on these substances administered in humans'. The nominator cited nine references; FDA characterised them as eight studies of α-MSH derivatives conducted IN ANIMALS, plus one study of skin permeation using HUMAN CADAVER SKIN. Cadaver skin in vitro is not administration to a living human, and it is the only 'human' reference in the nomination — the likeliest source of a false 'human data exists' claim. Independently re-checked against the ClinicalTrials.gov API on 2026-07-16: no registration of any kind administers KPV. Keyword queries return only diet and amino-acid studies matching lysine, proline and valine as separate free amino acids — noise, not trials. The affirmative evidence is nonclinical only: anti-inflammatory and wound-healing activity in rodent models and in vitro. Reviewers Böhm and Luger (2019), cited by FDA, drew the conclusion the market skips — that investigational clinical studies ARE NEEDED to determine whether KPV could be used to promote healing of skin wounds and ulcers. That is a statement of an open question, not of a demonstrated effect.", "source": { "url": "https://www.fda.gov/media/193346/download", "title": "KPV-Related Bulk Drug Substances — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, July 23-24, 2026", "publisher": "FDA", "date": "2026-07-23", "quote": "The nomination did not include, and FDA has not identified, any clinical studies or human exposure data for KPV via any route of administration. Therefore, potential safety risks associated with the use of KPV in humans are unknown." }, "verifiedAt": "2026-07-16" }, "fdaApproval": null, "fdaFindings": [ { "finding": "FDA staff propose not adding KPV (free base) or KPV acetate to the 503A Bulks List, ahead of the Pharmacy Compounding Advisory Committee meeting on 23-24 July 2026.", "note": "A staff proposal is not a final determination. The briefing document states: 'The FDA will not issue a final determination on the issues at hand until input from the advisory committee process has been considered and all reviews have been finalized.'", "source": { "url": "https://www.fda.gov/media/193346/download", "title": "KPV-Related Bulk Drug Substances — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, July 23-24, 2026", "publisher": "FDA", "date": "2026-07-23", "quote": "Accordingly, we propose not adding KPV (free base) or KPV acetate to the 503A Bulks List." }, "verifiedAt": "2026-07-16" }, { "finding": "FDA evaluated KPV only for the nominated uses — wound healing and inflammatory conditions (psoriasis, eczema) — in topical cream and gel form, and found a lack of evidence to evaluate effectiveness for either, noting that FDA-approved therapies with established efficacy already exist for both.", "note": "The gap between what was nominated and what is sold is the story here. FDA's own internet search recorded that 'websites promote KPV as single-API or multiple-API compounded drug products in oral, injectable, topical, and nasal spray formulations' and that 'KPV is promoted to treat inflammatory conditions, improve wound healing and skin health, and protect against nerve damage and stroke.' None of the oral, injectable or nasal routes was nominated, and neither nerve damage nor stroke was evaluated — no evidence was submitted for them and FDA identified none. This is an evidentiary vacuum, not a regulatory loophole. Inclusion on the 503A Bulks List is not necessarily limited to a specific use, so a 'do not add' outcome bars KPV for all of them regardless.", "source": { "url": "https://www.fda.gov/media/193346/download", "title": "KPV-Related Bulk Drug Substances — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, July 23-24, 2026", "publisher": "FDA", "date": "2026-07-23" }, "verifiedAt": "2026-07-16" }, { "finding": "FDA found that melanocortin receptors are unlikely to be the molecular targets underlying KPV's anti-inflammatory and wound-healing properties, and concluded that the molecular targets remain unknown.", "note": "This is the finding most directly at odds with how KPV is marketed. The standard vendor framing — KPV is an α-MSH fragment, therefore it acts through the melanocortin receptors that give α-MSH its anti-inflammatory effects — is contradicted by the studies FDA cites. In vitro, KPV failed to displace radiolabeled α-MSH binding at rat brain tissue, murine melanoma cells and MC1R-expressing murine macrophages (Lyson et al. 1994; Mandrika et al. 2001; Tatro and Entwistle 1994); unlike α-MSH, it did not raise cyclic AMP in MC1 receptor-expressing murine macrophages (Mandrika et al. 2001); and pharmacological and genetic approaches failed to implicate MC2, MC3 or MC4 receptors in KPV's effects (Getting et al. 2003). Researchers have PROPOSED other mechanisms — inhibition of NF-κB activation, inhibition of proinflammatory cytokines such as interleukin 1β, and PepT1-mediated uptake — but FDA records these as proposals, not established findings. Sharing a sequence with a molecule is not sharing its mechanism.", "source": { "url": "https://www.fda.gov/media/193346/download", "title": "KPV-Related Bulk Drug Substances — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, July 23-24, 2026", "publisher": "FDA", "date": "2026-07-23", "quote": "However, the molecular targets underlying the pharmacological effects of KPV-related BDSs remain unknown." }, "verifiedAt": "2026-07-16" }, { "finding": "FDA deemed both KPV (free base) and KPV acetate not well-characterized from a physical and chemical characterization perspective, citing naming conventions that do not follow established chemical nomenclature standards and an absence of quality-control attributes — impurities, aggregates and microbiological tests — in the published literature.", "note": "There is no USP or NF monograph for either substance, and neither is a component of any FDA-approved drug. FDA had to characterise the free base partly from chemical-supplier listings because the nomination contained no certificate of analysis for it. This finding is about identity and purity, not efficacy — it means that what is in a vial sold as 'KPV' is not established by any public standard.", "source": { "url": "https://www.fda.gov/media/193346/download", "title": "KPV-Related Bulk Drug Substances — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, July 23-24, 2026", "publisher": "FDA", "date": "2026-07-23" }, "verifiedAt": "2026-07-16" }, { "finding": "No registered outsourcing facility reported compounding any drug product containing KPV (free base) or KPV acetate to FDA between January 2017 and June 2025 — despite FDA's own internet search finding websites offering KPV from compounding pharmacies via telemedicine and online consultations.", "note": "Eight and a half years of mandatory reporting, zero reports. Outsourcing facilities register under section 503B and must list what they compounded every six months; the supply the market actually sees is therefore coming from somewhere other than the reporting channel. FDA notes the reports are retrospective and do not identify what a facility intends to produce in future — so this is a record of what was reported, not proof of what was made. Read alongside the second half of the same conclusion: 'the extent of KPV (free base) or KPV acetate use in compounding is unknown.'", "source": { "url": "https://www.fda.gov/media/193346/download", "title": "KPV-Related Bulk Drug Substances — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, July 23-24, 2026", "publisher": "FDA", "date": "2026-07-23", "quote": "According to OF reports submitted to the FDA, OFs have not reported preparing single or multiple-API compounded drug products containing KPV (free base) or KPV acetate from January 2017 to June 2025." }, "verifiedAt": "2026-07-16" }, { "finding": "The withdrawn nomination cited nine literature references in support of KPV; FDA characterised none of them as a study of KPV administered in humans.", "note": "The sentence to reach for when a vendor page cites 'the research'. FDA counted the citations and reported the count. Eight of the nine were studies of α-MSH derivatives conducted in animals; the ninth (Pawar et al. 2017) measured skin permeation across human cadaver skin in vitro. FDA also recorded that the references 'do not clearly identify whether the KPV form was a salt formulation or the free base' — so the nomination's own evidence base cannot be attributed to a specific substance.", "source": { "url": "https://www.fda.gov/media/193346/download", "title": "KPV-Related Bulk Drug Substances — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, July 23-24, 2026", "publisher": "FDA", "date": "2026-07-23", "quote": "The nomination cited nine literature references in support of the nomination; none were studies of KPV administered in humans." }, "verifiedAt": "2026-07-16" }, { "finding": "FDA identified no human pharmacokinetic or pharmacodynamic study of KPV (free base) or KPV acetate by any route, and no nonclinical pharmacokinetic or toxicokinetic study either.", "note": "Nothing is known about what happens to KPV in a human body: not absorption, not distribution, not metabolism, not elimination. This is the finding that makes route-switching indefensible. FDA evaluated a topical cream/gel at 0.1%, the only form nominated, and its single relevant permeation datum comes from cadaver skin in vitro. KPV is nonetheless promoted in oral, injectable and nasal spray forms, for which not even that datum exists.", "source": { "url": "https://www.fda.gov/media/193346/download", "title": "KPV-Related Bulk Drug Substances — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, July 23-24, 2026", "publisher": "FDA", "date": "2026-07-23", "quote": "FDA did not identify clinical studies in humans assessing pharmacokinetics or pharmacodynamics of KPV (free base) or KPV acetate via any route of administration." }, "verifiedAt": "2026-07-16" }, { "finding": "No pharmacopeia or foreign regulator recognises KPV. FDA searched the United States Pharmacopeia-National Formulary, the European Pharmacopoeia (11.8 edition, 2025) and the Japanese Pharmacopoeia (18th edition) and found no monograph for KPV (free base) or KPV acetate, and the European Medicines Agency lists no authorised product containing either.", "note": "Worth stating because 'available in other countries' is a standard move in this market. On the record FDA compiled, it is not — no monograph anywhere FDA looked, no EMA authorisation, and the nominator's own submission answered 'No' to whether the substance is recognised in foreign pharmacopeias or registered in other countries, and 'No' to whether information had been submitted to USP for monograph development.", "source": { "url": "https://www.fda.gov/media/193346/download", "title": "KPV-Related Bulk Drug Substances — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, July 23-24, 2026", "publisher": "FDA", "date": "2026-07-23" }, "verifiedAt": "2026-07-16" }, { "finding": "FDA recorded that KPV acetate forms Lys-Pro-diketopiperazine as a major degradation product under acid hydrolysis, alkaline hydrolysis and oxidative degradation, producing several additional nonpolar degradation products under basic conditions whose structures have not been elucidated.", "note": "A three-amino-acid peptide is not therefore a simple one. Under forced degradation reported in Pawar's Auburn University dissertation, oxidative treatment broke KPV acetate down rapidly into the diketopiperazine plus free proline and valine, and base produced three further products — DP1, DP2, DP3 — that the source does not structurally identify. Relevant because the certificate of analysis in the nomination reported a total impurity result against a limit but, in FDA's words, carried 'no information on the nature of single impurity'. Unknown degradants in a substance with no toxicity data are two absences that compound each other.", "source": { "url": "https://www.fda.gov/media/193346/download", "title": "KPV-Related Bulk Drug Substances — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, July 23-24, 2026", "publisher": "FDA", "date": "2026-07-23" }, "verifiedAt": "2026-07-16" } ], "safetySignals": [ { "signal": "No safety signals were found — because no human exposure data exists to generate any. The FAERS search through 2025-12-03 retrieved no reports, the medical-literature search identified no adverse-event cases, and the Human Foods Complaint System search covering 2004-01-01 to 2025-12-03 retrieved no cases where KPV was administered.", "note": "An empty FAERS result is the single most misreadable line in this document, and the inverse of a clean safety record. FDA's own conclusion from the same evidence base is that 'potential safety risks associated with the use in humans are unknown' — and FDA states it is 'particularly concerned about the lack of any human data'. Absence of reports here reflects absence of studied exposure, not absence of harm. FAERS also has structural limits FDA notes in the same document: reporting is voluntary, and the Agency does not receive all adverse event reports.", "source": { "url": "https://www.fda.gov/media/193346/download", "title": "KPV-Related Bulk Drug Substances — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, July 23-24, 2026", "publisher": "FDA", "date": "2026-07-23", "quote": "The FAERS search did not retrieve any reports and the literature search did not identify any cases of adverse events." }, "verifiedAt": "2026-07-16" }, { "signal": "FDA identified no nonclinical toxicity studies of KPV of any kind — no acute toxicity, no repeat-dose toxicity, no genotoxicity, no reproductive toxicity, no carcinogenicity, and no pharmacokinetic or toxicokinetic studies.", "note": "The absence is total: the safety base is empty in animals as well as in humans. FDA's conclusion is that it 'did not identify nonclinical toxicity studies to inform safety considerations for potential clinical uses'.", "source": { "url": "https://www.fda.gov/media/193346/download", "title": "KPV-Related Bulk Drug Substances — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, July 23-24, 2026", "publisher": "FDA", "date": "2026-07-23" }, "verifiedAt": "2026-07-16" }, { "signal": "FDA found insufficient data to conclude that KPV (free base) or KPV acetate do not present immunogenicity or aggregation risks.", "note": "Note the direction of the sentence — FDA is not asserting a risk, it is recording that the data needed to rule one out does not exist. Peptides may aggregate, and aggregation is a risk factor for immunogenicity; FDA cites work showing peptides as short as two amino acids can aggregate, so KPV's three-residue length does not exempt it. One consequence of an immune response FDA flags for peptide products generally is neutralising antibody activity, which could in principle neutralise the endogenous peptide counterpart.", "source": { "url": "https://www.fda.gov/media/193346/download", "title": "KPV-Related Bulk Drug Substances — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, July 23-24, 2026", "publisher": "FDA", "date": "2026-07-23" }, "verifiedAt": "2026-07-16" }, { "signal": "An in-vitro study in human cadaver skin reported that KPV does not permeate well through skin — which FDA notes could limit systemic toxicity from topical use, but equally could limit its usefulness as a topical agent by preventing distribution below the stratum corneum.", "note": "The double-edge is the point, and both edges are speculative. Pawar et al. (2017) reported that strategies breaching the skin's structural tightness — iontophoresis, microneedle abrasion — increased KPV penetration into inner epidermal layers of cadaver skin in vitro. FDA's caution is that it remains to be determined whether such strategies would also increase systemic absorption in vivo 'and, thereby, facilitate the development of untoward systemic effects'. The barrier that might make topical KPV safe is the same barrier that might make it inert, and defeating it may trade one for the other. Relevant because FDA found KPV promoted in oral, injectable and nasal spray forms, for which this topical reasoning offers no reassurance at all.", "source": { "url": "https://www.fda.gov/media/193346/download", "title": "KPV-Related Bulk Drug Substances — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, July 23-24, 2026", "publisher": "FDA", "date": "2026-07-23" }, "verifiedAt": "2026-07-16" } ], "faqs": [ { "question": "Is KPV legal in 2026?", "answer": "KPV is not on the FDA 503A Bulks List, which means it cannot lawfully be used as a bulk drug substance to compound drug products under section 503A. Verified against the list as updated 2026-05-14: KPV appears in none of the three categories and is absent from the document entirely. There is also no USP or National Formulary monograph for KPV (free base) or KPV acetate, and neither substance is a component of any FDA-approved drug.", "source": { "url": "https://www.fda.gov/media/94155/download", "title": "Bulk Drug Substances Nominated for Use in Compounding Under Section 503A of the Federal Food, Drug, and Cosmetic Act", "publisher": "FDA", "date": "2026-05-14" }, "verifiedAt": "2026-07-16" }, { "question": "Did KPV become legal again when the nomination for it was withdrawn?", "answer": "No. The withdrawal of the KPV nomination moved the substance sideways, not toward legality: a nomination is a request to be ADDED to the FDA 503A Bulks List, so withdrawing it leaves KPV off that list exactly as before, and off the list means not usable in 503A compounding. In KPV's case the withdrawal cut the other way entirely — FDA states that after the sole nomination was withdrawn it continued evaluating KPV (free base) and KPV acetate on its own initiative, and that it chose to do so because of its significant safety concerns.", "source": { "url": "https://www.fda.gov/media/193346/download", "title": "KPV-Related Bulk Drug Substances — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, July 23-24, 2026", "publisher": "FDA", "date": "2026-07-23", "quote": "The nomination was withdrawn, and FDA is evaluating the substances at its discretion. … Due to FDA's significant safety concerns related to this nomination/BDS, FDA is choosing to concurrently evaluate both BDSs (KPV (free base) and KPV acetate) …" }, "verifiedAt": "2026-07-16" }, { "question": "Is there any human evidence that KPV works?", "answer": "No. FDA states that the KPV nomination did not include, and that FDA has not identified, any clinical studies or human exposure data for KPV via any route of administration — a search that covered PubMed, Embase, ClinicalTrials.gov, DailyMed and Drugs@FDA. The evidence for KPV is nonclinical: rodent and in-vitro models of inflammation and wound healing. Reviewers Böhm and Luger (2019), cited by FDA, concluded that investigational clinical studies are needed to determine whether KPV could promote healing of skin wounds and ulcers.", "source": { "url": "https://www.fda.gov/media/193346/download", "title": "KPV-Related Bulk Drug Substances — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, July 23-24, 2026", "publisher": "FDA", "date": "2026-07-23", "quote": "The nomination did not include, and FDA has not identified, any clinical studies or human exposure data for KPV via any route of administration." }, "verifiedAt": "2026-07-16" }, { "question": "Is KPV safe?", "answer": "Unknown — and FDA says so in those terms. FDA's conclusion on KPV is that potential safety risks associated with its use in humans are unknown, because no human data exists to characterise them: no clinical studies, no case reports, no adverse event reports in FAERS through 2025-12-03, and no acute, repeat-dose, genotoxicity, reproductive or carcinogenicity studies in animals either. The empty adverse-event record reflects an absence of studied exposure, not a clean safety record; FDA states it is particularly concerned about the lack of any human data on drug products containing these substances administered via any route.", "source": { "url": "https://www.fda.gov/media/193346/download", "title": "KPV-Related Bulk Drug Substances — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, July 23-24, 2026", "publisher": "FDA", "date": "2026-07-23", "quote": "FDA is particularly concerned about the lack of any human data on drug products containing these substances administered via any route of administration, including lack of information to assess immunogenicity or aggregation of KPV-related bulk drug substances. Therefore, potential safety risks associated with the use in humans are unknown." }, "verifiedAt": "2026-07-16" }, { "question": "Can I get KPV from a compounding pharmacy?", "answer": "KPV cannot lawfully be compounded, because it is not on the FDA 503A Bulks List. FDA's own internet search nonetheless found websites offering KPV from compounding pharmacies through telemedicine and online consultations, promoting it as an injectable, oral, topical and nasal spray product, and in combination with BPC-157, TB-500, AOD-9604 and Follistatin-344. Against that, no registered outsourcing facility reported compounding any KPV-containing product to FDA between January 2017 and June 2025.", "source": { "url": "https://www.fda.gov/media/193346/download", "title": "KPV-Related Bulk Drug Substances — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, July 23-24, 2026", "publisher": "FDA", "date": "2026-07-23", "quote": "Results from an internet search for compounded drug products containing KPV (free base) or KPV acetate revealed that online websites offer options for obtaining KPV from compounding pharmacies through use of telemedicine and online consultations." }, "verifiedAt": "2026-07-16" }, { "question": "What did FDA propose at the July 2026 PCAC meeting about KPV?", "answer": "FDA staff proposed not adding KPV (free base) or KPV acetate to the 503A Bulks List, in a briefing document dated 2026-05-12 for the Pharmacy Compounding Advisory Committee meeting of 23-24 July 2026. The stated basis: the substances are not well-characterized from a physical and chemical characterization perspective, the extent of their use in compounding is unknown, there is no information on their administration in humans from which to draw conclusions about clinical safety or effectiveness, and FDA-approved therapies already exist for wounds and for inflammatory diseases. A staff proposal is not a final determination — FDA states it will not issue one until the advisory committee process has been considered and all reviews finalized.", "source": { "url": "https://www.fda.gov/media/193346/download", "title": "KPV-Related Bulk Drug Substances — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, July 23-24, 2026", "publisher": "FDA", "date": "2026-07-23", "quote": "Accordingly, we propose not adding KPV (free base) or KPV acetate to the 503A Bulks List." }, "verifiedAt": "2026-07-16" } ] }, { "slug": "leuprolide", "name": "Leuprolide", "aliases": [ "Lupron", "Lupron Depot", "Lupron Depot-PED", "Eligard", "Camcevi", "Fensolvi", "Lupaneta Pack", "Viadur", "leuprolide acetate", "leuprolide mesylate", "leuprorelin" ], "url": "https://peptides101.com/compounds/leuprolide", "moleculeNote": "A synthetic nonapeptide analogue of gonadotropin-releasing hormone (GnRH). The LUPRON DEPOT label describes it as 'a synthetic nonapeptide analog of naturally occurring gonadotropin-releasing hormone (GnRH)' whose chemical name is '5-oxo-L-prolyl-L-histidyl-L-tryptophyl-L-seryl-L-tyrosyl-D-leucyl-L-leucyl-L-arginyl-N-ethyl-L-prolinamide acetate (salt)'. THE SALT DISTINCTION HERE RUNS OPPOSITE TO SEMAGLUTIDE'S, which is why it is worth stating. Two different salts of this peptide are separately FDA-approved: leuprolide ACETATE (Lupron Depot, Lupron Depot-PED, Eligard, Fensolvi and the ANDA products) and leuprolide MESYLATE (Camcevi, NDA 211488 and NDA 219745). The CAMCEVI label gives the identical chemical name ending 'mesylate (salt)' rather than 'acetate (salt)', and Drugs@FDA classifies the original CAMCEVI submission as 'Type 2 - New Active Ingredient'. So a salt change is neither automatically disqualifying nor automatically equivalent: FDA treated the mesylate as a new active ingredient and required its own application, and that application was granted. The question is never whether a salt is 'the same drug' in the abstract — it is whether the specific salt in the specific product has an approved application behind it.", "quickAnswer": "Leuprolide is an FDA-approved prescription drug, not an unapproved research peptide: it is a synthetic nonapeptide gonadotropin-releasing hormone (GnRH) agonist that is the active ingredient in products approved under 27 applications in FDA's Drugs@FDA dataset — 17 NDAs and 10 ANDAs — the earliest of which, NDA 019010 (LUPRON injection), FDA states was initially approved on April 9, 1985. The approved indications are narrow and differ by product: Lupron Depot and Eligard are indicated for the treatment of advanced prostate cancer and Camcevi for the treatment of adult patients with advanced prostate cancer; Lupron Depot 3.75 mg for management of endometriosis and, with iron therapy, for preoperative hematologic improvement of women with anemia caused by fibroids; and Lupron Depot-PED and Fensolvi for the treatment of pediatric patients with central precocious puberty, Fensolvi's indication being gated on patients 2 years of age and older. None of the leuprolide labels recorded on this page carries an indication for gender dysphoria, fertility, anti-aging or body composition. FDA withdrew approval of one leuprolide application — NDA 203696, Lupaneta Pack — effective 23 May 2024, after the applicant stated the product was no longer marketed and requested withdrawal; FDA states that withdrawal is 'without prejudice to refiling', and the other twenty-six applications are unaffected. Leuprolide appears in none of Categories 1, 2 or 3 of FDA's 503A bulk drug substances list updated 14 May 2026, an absence that reflects an approved drug that was never on the compounding-nomination track rather than any status. The approved labeling carries substantial warnings, including tumor flare with possible spinal cord compression, cardiovascular and metabolic risk, loss of bone mineral density that the label states may not be fully reversible, and — on the pediatric labels — convulsions, severe cutaneous adverse reactions and pseudotumor cerebri.", "fdaStatus": { "value": "approved", "note": "FDA-approved, and approved widely — Drugs@FDA lists twenty-seven applications containing leuprolide acetate or leuprolide mesylate, seventeen NDAs and ten ANDAs, enumerated under fdaFindings. The status is not the interesting part of this record. Every one of those approvals is confined to a specific indication and a specific population, and the indications differ product by product: an advanced-prostate-cancer approval says nothing about a child, and a central-precocious-puberty approval says nothing about an adult. Read the approval record below before reading this badge.", "source": { "url": "https://nctr-crs.fda.gov/fdalabel/services/spl/set-ids/cbc8f94e-7330-4465-05ad-16d64493a5dd/spl-doc", "title": "LUPRON DEPOT (leuprolide acetate for depot suspension) — Prescribing Information (SPL)", "publisher": "FDA", "date": "2026-03-15", "quote": "LUPRON DEPOT is a gonadotropin releasing hormone (GnRH) agonist indicated for: treatment of advanced prostate cancer." }, "verifiedAt": "2026-08-02" }, "compoundingStatus": null, "evidence": { "tier": "proven-in-humans", "humanAdministrationChecked": true, "note": "ADMINISTRATION CHECK RUN, NOT ASSUMED. NCT00660010 was opened and read on 2026-08-02: intervention type DRUG, 'Lupron (leuprolide acetate)', administered by intramuscular injection to 55 paediatric participants with central precocious puberty; Phase 3; enrolment 55 ACTUAL; lead sponsor Abbott; status COMPLETED, primary completion 2009-04 ACTUAL, results first posted 2010-07-20. Leuprolide was GIVEN to human participants — it was not measured as an endogenous biomarker, which is the trap that reduces MOTS-c and TB-500 from an apparent five human RCTs to an actual zero. This registration is independently corroborated by the FDA-approved LUPRON DEPOT-PED label, which names the same NCT number in section 14.1 and reports the same participant count, so the registration is not carrying this claim alone. THE OTHER PIVOTAL PROGRAMMES, NAMED. Endometriosis: section 14.1 of the LUPRON DEPOT 3.75 mg label describes controlled clinical studies against an active comparator (danazol), in which a total of 166 women received LUPRON DEPOT 3.75 mg, plus two add-back studies in which 242 women were treated, one of them randomised and double-blind. Advanced prostate cancer: section 14.1 of the LUPRON DEPOT prostate label describes an 'open-label, non-comparative, multicenter clinical study' in 56 patients with stage D2 prostatic adenocarcinoma. READ THAT LAST ONE PRECISELY, BECAUSE IT IS THE WEAKEST LINK IN THE TIER. The prostate evidence recorded in that label section is single-arm and its primary objective was a SURROGATE — suppression of serum testosterone into the castrate range — with tumour response as a secondary endpoint. That is not a survival comparison, and this record does not claim one. The tier is carried by the paediatric and endometriosis programmes, which are controlled; the prostate section is reported here as what it says it is. SCOPE. The tier attaches to the approved products and the approved indications, and to nothing else. It does not transfer to any use outside those indications, and it does not transfer to material sold under this name that is not an approved product.", "source": { "url": "https://clinicaltrials.gov/study/NCT00660010", "title": "Study of Lupron Depot In The Treatment of Central Precocious Puberty", "publisher": "ClinicalTrials.gov", "date": "2011-04-12" }, "verifiedAt": "2026-08-02" }, "fdaApproval": { "applicationNumber": "NDA 019732 and NDA 020517 (Lupron Depot, advanced prostate cancer); NDA 019943 and NDA 020011 (Lupron Depot 3.75 mg) and NDA 020708 (Lupron Depot 11.25 mg, endometriosis and uterine fibroids); NDA 020263 (Lupron Depot-PED, central precocious puberty); NDA 021343, NDA 021379, NDA 021488 and NDA 021731 (Eligard); NDA 211488 and NDA 219745 (Camcevi, leuprolide mesylate); NDA 213150 (Fensolvi); NDA 205054 (leuprolide acetate for depot suspension); NDA 021088 (Viadur, discontinued); NDA 019010 (Lupron injection, the 1985 original, discontinued); NDA 203696 (Lupaneta Pack, approval withdrawn 2024)", "brandName": "Lupron Depot, Lupron Depot-PED, Eligard, Camcevi, Fensolvi", "approvedIndication": "LUPRON DEPOT is a gonadotropin releasing hormone (GnRH) agonist indicated for: treatment of advanced prostate cancer.", "discontinued": false, "source": { "url": "https://nctr-crs.fda.gov/fdalabel/services/spl/set-ids/cbc8f94e-7330-4465-05ad-16d64493a5dd/spl-doc", "title": "LUPRON DEPOT (leuprolide acetate for depot suspension) — Prescribing Information (SPL)", "publisher": "FDA", "date": "2026-03-15" }, "verifiedAt": "2026-08-02" }, "fdaFindings": [ { "finding": "Leuprolide acetate or leuprolide mesylate is the active ingredient in products approved under 27 applications in FDA's Drugs@FDA dataset — 17 NDAs and 10 ANDAs. The earliest is NDA 019010 (LUPRON injection), which FDA states was initially approved on April 9, 1985.", "note": "The application count is from the Drugs@FDA query recorded in this file's source block, run on 2026-08-02 and returning 27 results; the 1985 approval date is quoted from the Federal Register notice cited here, which is a stronger source for it than a database field. NDAs: 019010, 019732, 019943, 020011, 020263, 020517, 020708, 021088, 021343, 021379, 021488, 021731, 203696, 205054, 211488, 213150, 219745. ANDAs: 074728, 075471, 075721, 078885, 212963, 213829, 215336, 215826, 217437, 217957. A METHOD NOTE THAT MATTERS MORE THAN THE COUNT. Querying openFDA on `openfda.generic_name` returns 20 of these; querying `products.active_ingredients.name` returns all 27. The seven the first query drops include both CAMCEVI applications and LUPANETA PACK — that is, the entire leuprolide mesylate franchise and the one application FDA actually withdrew. A NOT_FOUND or a short count from the wrong field is an artifact of the query, never a fact about the database.", "source": { "url": "https://www.federalregister.gov/documents/2019/05/30/2019-11243/determination-that-lupron-leuprolide-acetate-injection-1-milligram02-milliliter-was-not-withdrawn", "title": "Determination That LUPRON (Leuprolide Acetate) Injection, 1 Milligram/0.2 Milliliter, Was Not Withdrawn From Sale for Reasons of Safety or Effectiveness", "publisher": "Federal Register (FDA)", "date": "2019-05-30", "quote": "LUPRON (leuprolide acetate) injection, 1 mg/0.2 mL, is the subject of NDA 019010, held by Abbvie Endocrine, Inc., and initially approved on April 9, 1985." }, "verifiedAt": "2026-08-02" }, { "finding": "LUPRON DEPOT 3.75 mg is indicated for management of endometriosis, including pain relief and reduction of endometriotic lesions; in combination with norethindrone acetate for initial management of the painful symptoms of endometriosis and for management of recurrence of symptoms; and, used concomitantly with iron therapy, for the preoperative hematologic improvement of women with anemia caused by fibroids for whom three months of hormonal suppression is deemed necessary.", "note": "Recorded verbatim because the fibroid indication is routinely reported as 'approved for fibroids', and the label does not say that. What it approves is PREOPERATIVE HEMATOLOGIC IMPROVEMENT of women with anemia caused by fibroids — a haematological indication ahead of surgery, used with iron, not a treatment for the fibroids themselves. The label goes further and tells the prescriber to try iron first: 'Consider a one-month trial period on iron alone, as some women will respond to iron alone.' The same label carries an explicit Limitation of Use stating the product is not indicated for combination use with norethindrone acetate add-back therapy in that preoperative setting. The corresponding LUPRON DEPOT 11.25 mg label (NDA 020708) carries the same two indications in the same wording. Treatment duration is capped by bone-density risk — see safetySignals.", "source": { "url": "https://nctr-crs.fda.gov/fdalabel/services/spl/set-ids/00c486b0-bd7b-4898-834d-8c656e5e73cb/spl-doc", "title": "LUPRON DEPOT 3.75 mg (leuprolide acetate for depot suspension) — Prescribing Information (SPL)", "publisher": "FDA", "date": "2025-09-18", "quote": "LUPRON DEPOT 3.75 mg is a gonadotropin-releasing hormone (GnRH) agonist indicated for: Endometriosis … Management of endometriosis, including pain relief and reduction of endometriotic lesions. … In combination with a norethindrone acetate for initial management of the painful symptoms of endometriosis and for management of recurrence of symptoms. … Uterine Leiomyomata (Fibroids) … Concomitant use with iron therapy for preoperative hematologic improvement of women with anemia caused by fibroids for whom three months of hormonal suppression is deemed necessary." }, "verifiedAt": "2026-08-02" }, { "finding": "LUPRON DEPOT-PED is indicated for the treatment of pediatric patients with central precocious puberty (CPP).", "note": "The entire paediatric indication, in one sentence. Central precocious puberty is a diagnosis: premature activation of the hypothalamic-pituitary-gonadal axis. It is the only paediatric condition this label approves the product for. Any other use in a child is use outside the approved indication, which is a decision for a licensed prescriber and is not something this label supports — and this site's position on off-label use is the same here as everywhere else: we record what the label says and we do not extend it.", "source": { "url": "https://nctr-crs.fda.gov/fdalabel/services/spl/set-ids/e99f47d2-da10-3127-ecb3-e5d942ae6e81/spl-doc", "title": "LUPRON DEPOT-PED (leuprolide acetate for depot suspension) — Prescribing Information (SPL)", "publisher": "FDA", "date": "2025-11-14", "quote": "LUPRON DEPOT-PED is a gonadotropin releasing hormone (GnRH) agonist indicated for the treatment of pediatric patients with central precocious puberty. ( 1 )" }, "verifiedAt": "2026-08-02" }, { "finding": "FENSOLVI is indicated for the treatment of pediatric patients 2 years of age and older with central precocious puberty (CPP).", "note": "Recorded alongside LUPRON DEPOT-PED because the two paediatric leuprolide products do not carry identical indications, and the difference is a hard number: FENSOLVI's indication is gated on 'pediatric patients 2 years of age and older', while LUPRON DEPOT-PED's is not age -gated in its indication statement. Same molecule, same condition, different approved populations, different routes (FENSOLVI subcutaneous, LUPRON DEPOT-PED intramuscular). Neither is substitutable for the other on the strength of the other's label.", "source": { "url": "https://nctr-crs.fda.gov/fdalabel/services/spl/set-ids/2c311700-edf4-4f2a-a468-9875489a6cc7/spl-doc", "title": "FENSOLVI (leuprolide acetate) for injectable suspension — Prescribing Information (SPL)", "publisher": "FDA", "date": "2025-09-25", "quote": "FENSOLVI is a gonadotropin releasing hormone (GnRH) agonist indicated for the treatment of pediatric patients 2 years of age and older with central precocious puberty." }, "verifiedAt": "2026-08-02" }, { "finding": "ELIGARD is indicated for the treatment of advanced prostate cancer. CAMCEVI, which contains leuprolide mesylate rather than leuprolide acetate, is indicated for the treatment of adult patients with advanced prostate cancer.", "note": "The ELIGARD sentence in the value above is verbatim from the ELIGARD SPL (effectiveTime 2026-04-30), a separate document from this entry's source, and reads in full: 'ELIGARD is a gonadotropin releasing hormone (GnRH) agonist indicated for the treatment of advanced prostate cancer.' Both are recorded because the prostate-cancer indication is held by three separate franchises under nine NDAs, not by one product. Note CAMCEVI's narrower wording — 'adult patients' — which the LUPRON DEPOT and ELIGARD prostate indications do not contain. ONE DOCUMENTED CHANGE, REPORTED AS AN OBSERVATION AND NOT AS A CONCLUSION: the ELIGARD SPL carrying effectiveTime 2019-04-29 reads 'palliative treatment of advanced prostate cancer', and the current one drops the word 'palliative'. The 2019 Federal Register notice cited elsewhere on this record likewise describes the original LUPRON injection as 'indicated for palliative treatment of advanced prostatic cancer'. This record does not assert why the word changed, and no finding here depends on it.", "source": { "url": "https://nctr-crs.fda.gov/fdalabel/services/spl/set-ids/d7a8761a-d953-413a-e053-2a95a90a60ee/spl-doc", "title": "CAMCEVI (leuprolide mesylate) injectable emulsion — Prescribing Information (SPL)", "publisher": "FDA", "date": "2026-02-18", "quote": "CAMCEVI is a gonadotropin-releasing hormone (GnRH) agonist indicated for the treatment of adult patients with advanced prostate cancer." }, "verifiedAt": "2026-08-02" }, { "finding": "FDA withdrew approval of NDA 203696 (Lupaneta Pack, leuprolide acetate injection and norethindrone acetate tablets, AbbVie Endocrinology Inc.) effective May 23, 2024. FDA states the applicants informed it that the products were no longer marketed and requested withdrawal, that they waived their opportunity for a hearing, and that withdrawal under 21 CFR 314.150(c) is without prejudice to refiling.", "note": "A REAL WITHDRAWAL OF A REAL LEUPROLIDE APPLICATION, and the reason this record's fdaStatus is still 'approved' rather than 'approval-withdrawn'. The withdrawal is scoped to one application out of twenty-seven; sixteen other NDAs and ten ANDAs are untouched. A record that reported this as 'leuprolide's approval was withdrawn' would be false, and a record that omitted it would be hiding the one document that complicates the badge. Read the mechanism, not the headline. This is a Sec. 314.150(c) withdrawal — applicant-requested, on the stated ground that the product is no longer marketed. FDA is not reported here as making any finding about the product's safety or effectiveness, and this record makes none either. Note also what Drugs@FDA shows: NDA 203696's products carry marketing status 'Discontinued', the same string used for products whose approvals are intact. That field does not distinguish 'discontinued' from 'approval withdrawn'. The Federal Register does. The withdrawn product was the endometriosis add-back combination — leuprolide packaged with norethindrone acetate — which is the exact regimen the surviving LUPRON DEPOT 3.75 mg label still describes and still indicates. The combination therapy did not stop being approved; the co-packaged product stopped being sold.", "source": { "url": "https://www.federalregister.gov/documents/2024/04/23/2024-08657/pai-holdings-llc-dba-pharmaceutical-associates-inc-et-al-withdrawal-of-approval-of-23-new-drug", "title": "PAI Holdings, LLC DBA Pharmaceutical Associates, Inc., et al.; Withdrawal of Approval of 23 New Drug Applications", "publisher": "Federal Register (FDA)", "date": "2024-04-23", "quote": "The applicants listed in the table have informed FDA that these drug products are no longer marketed and have requested that FDA withdraw approval of the applications under the process in Sec. 314.150(c) (21 CFR 314.150(c)). The applicants have also, by their requests, waived their opportunity for a hearing. Withdrawal of approval of an application or abbreviated application under Sec. 314.150(c) is without prejudice to refiling." }, "verifiedAt": "2026-08-02" }, { "finding": "FDA determined that LUPRON (leuprolide acetate) injection, 1 mg/0.2 mL — NDA 019010, the original 1985 leuprolide product — was not withdrawn from sale for reasons of safety or effectiveness, and continues to list it in the Discontinued Drug Product List section of the Orange Book.", "note": "RECORDED BECAUSE THIS IS THE EXACT DOCUMENT TYPE THIS VERTICAL INVERTS. Sermorelin's sellers take a 'not withdrawn for reasons of safety or effectiveness' determination and sell it as an FDA endorsement. It is not one, and the notice says so structurally: FDA explains the finding exists so that generic applications referring to the listed drug can continue to be approved, and states 'This determination means that FDA will not begin procedures to withdraw approval of abbreviated new drug applications (ANDAs) that refer to this drug product.' It is a housekeeping determination about the Orange Book, made on a citizen petition filed by a generic manufacturer (Hetero Labs Limited, Docket FDA-2018-P-4851). It says nothing about whether the product works and nothing about any unapproved use. It does carry one fact worth having: FDA describes this product as 'indicated for palliative treatment of advanced prostatic cancer' — the 1985 approval was oncology, not endocrinology, and every other indication leuprolide now holds came later.", "source": { "url": "https://www.federalregister.gov/documents/2019/05/30/2019-11243/determination-that-lupron-leuprolide-acetate-injection-1-milligram02-milliliter-was-not-withdrawn", "title": "Determination That LUPRON (Leuprolide Acetate) Injection, 1 Milligram/0.2 Milliliter, Was Not Withdrawn From Sale for Reasons of Safety or Effectiveness", "publisher": "Federal Register (FDA)", "date": "2019-05-30", "quote": "After considering the citizen petition and reviewing Agency records and based on the information we have at this time, FDA has determined under Sec. 314.161 that LUPRON (leuprolide acetate) injection, 1 mg/0.2 mL, was not withdrawn for reasons of safety or effectiveness. … We have found no information that would indicate that this drug product was withdrawn from sale for reasons of safety or effectiveness." }, "verifiedAt": "2026-08-02" }, { "finding": "Leuprolide appears in none of Categories 1, 2 or 3 of FDA's list of bulk drug substances nominated for use in compounding under section 503A, updated 2026-05-14.", "note": "Recorded to close a misreading, not to assert a status — which is also why this record has no compoundingStatus field. Verified by fetching the document with a browser user-agent and text-extracting all seven pages locally on 2026-08-02: zero hits for 'leuprolide' anywhere in it. This absence means something entirely different from BPC-157's absence. BPC-157 was nominated, sat in Category 2, and left when the nominators withdrew. Leuprolide was never in this system at all — a 503A bulks nomination is a route for substances WITHOUT an approved product, and leuprolide is the active ingredient in twenty-six that survive. Categorical silence here is neither permission nor a safety finding, and asserting 'never-nominated' as a status would imply a proceeding leuprolide was never part of.", "source": { "url": "https://www.fda.gov/media/94155/download", "title": "Bulk Drug Substances Nominated for Use in Compounding Under Section 503A of the Federal Food, Drug, and Cosmetic Act", "publisher": "FDA", "date": "2026-05-14" }, "verifiedAt": "2026-08-02" } ], "safetySignals": [ { "signal": "Tumor flare. The LUPRON DEPOT prostate label states that, like other GnRH agonists, the product causes an initial increase in serum testosterone during the first weeks of treatment; that patients may experience worsening of symptoms or onset of new signs and symptoms including bone pain, neuropathy, hematuria or bladder outlet obstruction; and that spinal cord compression may contribute to paralysis with or without fatal complications.", "note": "The mechanistic point that anyone reading 'GnRH agonist' as 'hormone suppressant' will miss. A GnRH agonist STIMULATES before it suppresses, and in a man with metastatic vertebral disease that transient surge is the dangerous part of the treatment. The label directs close monitoring of patients with metastatic vertebral lesions or urinary tract obstruction. The same initial rise appears on the paediatric labels as 'Initial Rise of Gonadotropins and Sex Steroid Levels', where it presents instead as a transient increase in signs of puberty including vaginal bleeding.", "source": { "url": "https://nctr-crs.fda.gov/fdalabel/services/spl/set-ids/cbc8f94e-7330-4465-05ad-16d64493a5dd/spl-doc", "title": "LUPRON DEPOT (leuprolide acetate for depot suspension) — Prescribing Information (SPL)", "publisher": "FDA", "date": "2026-03-15", "quote": "Patients may experience worsening of symptoms or onset of new signs and symptoms during the first few weeks of treatment, including bone pain, neuropathy, hematuria, or bladder outlet obstruction. Spinal cord compression may contribute to paralysis with or without fatal complications." }, "verifiedAt": "2026-08-02" }, { "signal": "Metabolic and cardiovascular warnings on the prostate-cancer label: FDA-approved labeling states that use of GnRH agonists may lead to metabolic changes such as hyperglycemia, diabetes mellitus and hyperlipidemia, with non-alcoholic fatty liver disease including cirrhosis occurring in the post-marketing setting; that increased risk of developing myocardial infarction, sudden cardiac death and stroke has been reported in association with use of GnRH agonists in men; and that androgen deprivation therapy may prolong the QT/QTc interval.", "note": "Quoted with FDA's own qualifier attached — 'The risk appears low based on the reported odds ratios' — because dropping that clause turns a labelled precaution into a scare, and keeping it while dropping the risk turns a labelled precaution into nothing. Both misreadings circulate. The label's instruction is monitoring, not avoidance.", "source": { "url": "https://nctr-crs.fda.gov/fdalabel/services/spl/set-ids/cbc8f94e-7330-4465-05ad-16d64493a5dd/spl-doc", "title": "LUPRON DEPOT (leuprolide acetate for depot suspension) — Prescribing Information (SPL)", "publisher": "FDA", "date": "2026-03-15", "quote": "Increased risk of developing myocardial infarction, sudden cardiac death and stroke has been reported in association with use of GnRH agonists in men. The risk appears low based on the reported odds ratios, and should be evaluated carefully along with cardiovascular risk factors when determining a treatment for patients with prostate cancer." }, "verifiedAt": "2026-08-02" }, { "signal": "Loss of bone mineral density, some of which may not be reversible after stopping treatment. The LUPRON DEPOT 3.75 mg label states that the product induces a hypoestrogenic state resulting in loss of bone mineral density, that the duration of treatment is limited by that risk, that combination use of norethindrone acetate is effective in reducing the loss, that the product is not to be used again without combination norethindrone acetate, and that bone mineral density is to be assessed before retreatment.", "note": "The clause that carries the weight is 'some of which may not be reversible after stopping treatment'. This is why the same label caps total therapy duration by a Limitation of Use rather than leaving it to judgement, and it is the reason add-back therapy exists at all. The label also flags additional risk in women with major risk factors for decreased BMD — chronic alcohol use, tobacco use, strong family history of osteoporosis, or chronic use of drugs that can decrease BMD such as anticonvulsants or corticosteroids.", "source": { "url": "https://nctr-crs.fda.gov/fdalabel/services/spl/set-ids/00c486b0-bd7b-4898-834d-8c656e5e73cb/spl-doc", "title": "LUPRON DEPOT 3.75 mg (leuprolide acetate for depot suspension) — Prescribing Information (SPL)", "publisher": "FDA", "date": "2025-09-18", "quote": "LUPRON DEPOT 3.75 mg induces a hypoestrogenic state that results in loss of bone mineral density (BMD), some of which may not be reversible after stopping treatment." }, "verifiedAt": "2026-08-02" }, { "signal": "Paediatric warnings and precautions on both approved paediatric labels: psychiatric events reported in patients taking GnRH agonists, including emotional lability such as crying, irritability, impatience, anger and aggression; postmarketing reports of convulsions in patients with and without predisposing conditions; severe cutaneous adverse reactions including Stevens-Johnson syndrome / toxic epidermal necrolysis, DRESS and AGEP, including cases with visceral involvement and/or requiring skin grafts; and pseudotumor cerebri (idiopathic intracranial hypertension).", "note": "All four appear in section 5 of the LUPRON DEPOT-PED label quoted here, and all four appear in the same order in section 5 of the FENSOLVI label — verified against both documents on 2026-08-02. The convulsions entry is worth reading closely: the label reports them in patients with predisposing conditions AND, separately, 'in the absence of any of the conditions mentioned above'. Both paediatric labels are also contraindicated in pregnancy and state the product may cause fetal harm.", "source": { "url": "https://nctr-crs.fda.gov/fdalabel/services/spl/set-ids/e99f47d2-da10-3127-ecb3-e5d942ae6e81/spl-doc", "title": "LUPRON DEPOT-PED (leuprolide acetate for depot suspension) — Prescribing Information (SPL)", "publisher": "FDA", "date": "2025-11-14", "quote": "Convulsions: Have been observed in patients with or without a history of seizures, epilepsy, cerebrovascular disorders, central nervous system anomalies or tumors, and in patients on concomitant medications that have been associated with convulsions. … Pseudotumor Cerebri (Idiopathic Intracranial Hypertension): Have been reported in pediatric patients receiving GnRH agonists, including LUPRON DEPOT-PED. Monitor patients for headache, papilledema, and blurred vision." }, "verifiedAt": "2026-08-02" }, { "signal": "FDA has stated that it added a warning about the risk of pseudotumor cerebri (idiopathic intracranial hypertension) to the labeling for GnRH agonists approved for the treatment of central precocious puberty in pediatric patients, following a review of post-marketing safety data, the FDA Adverse Event Reporting System and the literature. FDA reported six cases supporting a plausible association, all in birth-assigned females ages 5 to 12, of which five were undergoing treatment for central precocious puberty and one for transgender care, and stated the incidence rate could not be reliably established due to the small number of cases and data limitations.", "note": "Recorded with FDA's own limitation attached and nothing added. Six spontaneously reported cases with no denominator is not a rate, and FDA says so in the same document — anyone quoting the six as an incidence is inventing the part that matters. What the six DO establish is why the warning was added, and the labelling change itself is independently confirmed in section 5.5 of both paediatric labels on this record. The one detail worth stating plainly rather than eliding: FDA's own case series records that one of the six patients was receiving a GnRH agonist for transgender care, which is a use no leuprolide label on this record carries an indication for. This site's rule applies unchanged in both directions — we report what the document says, we do not extrapolate from six cases to a population, and we take no position on a clinical decision that belongs to a patient, a family and a licensed prescriber. PROVENANCE, because it is not a standard FDA webpage: the document is hosted at fda.gov/media/159663/download, is headed 'from the Food and Drug Administration', is typed 'FDA Update', names the three FDA offices that contributed, and carries a 2022 American Academy of Pediatrics copyright line. It is FDA-authored content published in AAP News.", "source": { "url": "https://www.fda.gov/media/159663/download", "title": "Risk of pseudotumor cerebri added to labeling for gonadotropin-releasing hormone agonists", "publisher": "FDA", "date": "2022-07-01", "quote": "Six cases were identified that supported a plausible association between GnRH agonist use and pseudotumor cerebri. All six cases were reported in birth-assigned females ages 5 to 12 years. Five were undergoing treatment for central precocious puberty and one for transgender care. … The incidence rate of pseudotumor cerebri associated with GnRH agonist use in pediatric patients could not be reliably established due to the small number of cases and data limitations." }, "verifiedAt": "2026-08-02" } ], "faqs": [ { "question": "Is leuprolide FDA-approved?", "answer": "Yes. Leuprolide is the active ingredient in FDA-approved prescription drug products, and has been since 1985. The FDA-approved labeling for LUPRON DEPOT states that it 'is a gonadotropin releasing hormone (GnRH) agonist indicated for: treatment of advanced prostate cancer.' FDA's Drugs@FDA dataset lists 27 applications containing leuprolide acetate or leuprolide mesylate — 17 new drug applications and 10 abbreviated new drug applications — under brand names including Lupron Depot, Lupron Depot-PED, Eligard, Camcevi and Fensolvi, plus generic leuprolide acetate injection. What that approval does not do is travel. Each application is approved for specific indications in specific populations, and those indications differ product by product: the prostate-cancer labels say nothing about children, and the central-precocious-puberty labels say nothing about adults. 'Leuprolide is approved' is true and is not an answer to 'is this product approved for this person'.", "source": { "url": "https://nctr-crs.fda.gov/fdalabel/services/spl/set-ids/cbc8f94e-7330-4465-05ad-16d64493a5dd/spl-doc", "title": "LUPRON DEPOT (leuprolide acetate for depot suspension) — Prescribing Information (SPL)", "publisher": "FDA", "date": "2026-03-15", "quote": "LUPRON DEPOT is a gonadotropin releasing hormone (GnRH) agonist indicated for: treatment of advanced prostate cancer." }, "verifiedAt": "2026-08-02" }, { "question": "Is Lupron approved for endometriosis?", "answer": "Yes — but by a different product and a different application than the prostate-cancer Lupron Depot, and the fibroid indication people usually pair it with is narrower than it sounds. The FDA-approved labeling for LUPRON DEPOT 3.75 mg states it is a GnRH agonist indicated for 'Management of endometriosis, including pain relief and reduction of endometriotic lesions' and, 'In combination with a norethindrone acetate for initial management of the painful symptoms of endometriosis and for management of recurrence of symptoms.' The same label's second indication is not a treatment for uterine fibroids: it is 'Concomitant use with iron therapy for preoperative hematologic improvement of women with anemia caused by fibroids for whom three months of hormonal suppression is deemed necessary' — a haematological indication ahead of surgery. The label also tells prescribers to 'Consider a one-month trial period on iron alone, as some women will respond to iron alone.' Total therapy duration is capped by an explicit Limitation of Use because of bone mineral density loss, which the label states may not be fully reversible.", "source": { "url": "https://nctr-crs.fda.gov/fdalabel/services/spl/set-ids/00c486b0-bd7b-4898-834d-8c656e5e73cb/spl-doc", "title": "LUPRON DEPOT 3.75 mg (leuprolide acetate for depot suspension) — Prescribing Information (SPL)", "publisher": "FDA", "date": "2025-09-18", "quote": "Uterine Leiomyomata (Fibroids) … Concomitant use with iron therapy for preoperative hematologic improvement of women with anemia caused by fibroids for whom three months of hormonal suppression is deemed necessary. … Limitations of Use: LUPRON DEPOT 3.75 mg is not indicated for combination use with norethindrone acetate add-back therapy for the preoperative hematologic improvement of women with anemia caused by heavy menstrual bleeding due to fibroids." }, "verifiedAt": "2026-08-02" }, { "question": "Is Lupron approved as a puberty blocker for gender dysphoria?", "answer": "No. The approved paediatric indication for leuprolide is central precocious puberty, and only that. FDA-approved labeling states that 'LUPRON DEPOT-PED is a gonadotropin releasing hormone (GnRH) agonist indicated for the treatment of pediatric patients with central precocious puberty', and that 'FENSOLVI is a gonadotropin releasing hormone (GnRH) agonist indicated for the treatment of pediatric patients 2 years of age and older with central precocious puberty.' Neither label carries an indication for gender dysphoria. FDA is aware the drugs are used in that setting and has said so in its own words: in describing the safety review that added a pseudotumor cerebri warning to GnRH agonist labeling, FDA reported six cases and stated that 'Five were undergoing treatment for central precocious puberty and one for transgender care.' Use of an approved drug outside its approved indication is off-label use, which is lawful for a licensed prescriber and is a clinical decision for a patient, a family and that prescriber. What can be said from the documents is narrow and worth saying exactly: no leuprolide label recorded on this page has been reviewed and approved by FDA for this use, so the efficacy and safety findings in those labels are not findings about it.", "source": { "url": "https://nctr-crs.fda.gov/fdalabel/services/spl/set-ids/2c311700-edf4-4f2a-a468-9875489a6cc7/spl-doc", "title": "FENSOLVI (leuprolide acetate) for injectable suspension — Prescribing Information (SPL)", "publisher": "FDA", "date": "2025-09-25", "quote": "FENSOLVI is a gonadotropin releasing hormone (GnRH) agonist indicated for the treatment of pediatric patients 2 years of age and older with central precocious puberty." }, "verifiedAt": "2026-08-02" }, { "question": "Did the FDA withdraw approval of Lupron?", "answer": "One leuprolide application, not the drug. FDA withdrew approval of NDA 203696 — Lupaneta Pack, the co-packaged leuprolide acetate injection and norethindrone acetate tablets from AbbVie Endocrinology Inc. — effective 23 May 2024. FDA states the reason on the record: the applicants 'informed FDA that these drug products are no longer marketed and have requested that FDA withdraw approval of the applications', waived their opportunity for a hearing, and that the withdrawal 'is without prejudice to refiling'. FDA is not reported in that notice as making any finding about the product's safety or effectiveness. The other 26 leuprolide applications in Drugs@FDA are unaffected and Lupron Depot, Lupron Depot-PED, Eligard, Camcevi and Fensolvi remain approved and marketed. Two other leuprolide products are off the market without any withdrawal of approval: Viadur, and the original 1985 LUPRON injection under NDA 019010, which FDA determined 'was not withdrawn for reasons of safety or effectiveness' and continues to list in the Discontinued Drug Product List section of the Orange Book. That determination is a housekeeping finding that lets generic applications referring to the product continue to be approved — it is not an FDA endorsement of the product, and it is regularly sold as one.", "source": { "url": "https://www.federalregister.gov/documents/2024/04/23/2024-08657/pai-holdings-llc-dba-pharmaceutical-associates-inc-et-al-withdrawal-of-approval-of-23-new-drug", "title": "PAI Holdings, LLC DBA Pharmaceutical Associates, Inc., et al.; Withdrawal of Approval of 23 New Drug Applications", "publisher": "Federal Register (FDA)", "date": "2024-04-23", "quote": "The applicants listed in the table have informed FDA that these drug products are no longer marketed and have requested that FDA withdraw approval of the applications under the process in Sec. 314.150(c) (21 CFR 314.150(c)). … Withdrawal of approval of an application or abbreviated application under Sec. 314.150(c) is without prejudice to refiling." }, "verifiedAt": "2026-08-02" }, { "question": "Is leuprolide on FDA's 503A bulk drug substances list?", "answer": "No — leuprolide appears in none of Categories 1, 2 or 3 of FDA's list of bulk drug substances nominated for use in compounding under section 503A, in the version updated 14 May 2026. That was verified by fetching the document from FDA with a browser user-agent and text-extracting all seven pages: zero hits for 'leuprolide' anywhere in it. Read that absence correctly, because it means the opposite of what the same absence means for a research peptide. The 503A nomination process is a route for bulk substances that are not components of approved drug products; leuprolide is the active ingredient in 26 currently approved applications, so it was never on that track at all. Its absence is therefore not a withdrawal, not a rejection, and not a safety finding — it is a substance that was never in the proceeding. This site records no 503A compounding status for leuprolide for exactly that reason: asserting one would imply a process it was never part of.", "source": { "url": "https://www.fda.gov/media/94155/download", "title": "Bulk Drug Substances Nominated for Use in Compounding Under Section 503A of the Federal Food, Drug, and Cosmetic Act", "publisher": "FDA", "date": "2026-05-14" }, "verifiedAt": "2026-08-02" } ] }, { "slug": "linaclotide", "name": "Linaclotide", "aliases": [ "Linzess" ], "url": "https://peptides101.com/compounds/linaclotide", "moleculeNote": "A 14-amino acid peptide and a guanylate cyclase-C (GC-C) agonist. Three things about it cut against the defaults of the peptide market. (1) ROUTE — it is an oral capsule, not an injection. LINZESS is supplied as capsules of 72 mcg, 145 mcg and 290 mcg; those strengths identify the product, and this site publishes no dosing. (2) EXPOSURE — the label states 'LINZESS is minimally absorbed with negligible systemic availability following oral administration', and that plasma concentrations of linaclotide and its active metabolite are below the limit of quantitation, so standard pharmacokinetic parameters cannot be calculated for it. A systemic peptide this is not. (3) TARGET — the label describes linaclotide as structurally related to human guanylin and uroguanylin, binding GC-C and acting locally on the luminal surface of the intestinal epithelium. The molecule most people mean when they say 'peptide' is a systemic injectable; this one works in the gut lumen and is largely recovered in stool as its active metabolite.", "quickAnswer": "Linaclotide is an FDA-approved drug, marketed as Linzess capsules under NDA 202811 and taken orally rather than injected. Its approved labeling covers three indications with three different age floors: irritable bowel syndrome with constipation in adults and pediatric patients 7 years of age and older, chronic idiopathic constipation in adults only, and functional constipation in pediatric patients 2 years of age and older. The label carries a boxed warning stating that 'LINZESS is contraindicated in patients less than 2 years of age; in neonatal mice, linaclotide caused deaths due to dehydration' — a warning that stops exactly where the youngest approved indication begins. The original 2012 label was adults-only and its boxed warning then contraindicated pediatric patients up to 6 years of age and told prescribers to avoid use in patients 6 through 17. Efficacy in adults was established in two randomised, double-blind, placebo-controlled Phase 3 trials, where the label reports combined responder rates of 12% versus 5% on placebo and 13% versus 3%; the pediatric IBS-C indication rests on an analysis with no placebo comparator. Linaclotide appears in none of Categories 1, 2 or 3 of FDA's 503A bulk drug substances list updated 14 May 2026, an absence that reflects its position as the active ingredient of an approved drug rather than any finding about it.", "fdaStatus": { "value": "approved", "note": "FDA-approved under NDA 202811, originally approved 2012-08-30 as a Type 1 New Molecular Entity. Cross-checked against Drugs@FDA on 2026-08-02: NDA 202811, sponsor listed as ABBVIE (openFDA manufacturer field still reads 'Allergan, Inc.'), three LINZESS capsule products, all marketing status Prescription, none discontinued. Drugs@FDA lists twenty submissions under this application, all with status AP, of which five are efficacy supplements (submission numbers 10, 16, 21, 22 and 23); the most recent, supplement 23, was approved 2026-05-21. Approval is always for a specific indication and population — read the approval record below, because the indications here are narrower and stranger than the one-line 'IBS drug' summary suggests.", "source": { "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2026/202811s023lbl.pdf", "title": "LINZESS (linaclotide) capsules — Highlights of Prescribing Information (NDA 202811, s023)", "publisher": "FDA", "date": "2026-05-22", "quote": "LINZESS® (linaclotide) capsules, for oral use … Initial U.S. Approval: 2012 … LINZESS is a guanylate cyclase-C agonist indicated for treatment of: • Irritable bowel syndrome with constipation (IBS-C) in adults and pediatric patients 7 years of age and older. • Chronic idiopathic constipation (CIC) in adults. • Functional constipation (FC) in pediatric patients 2 years of age and older." }, "verifiedAt": "2026-08-02" }, "compoundingStatus": null, "evidence": { "tier": "proven-in-humans", "humanAdministrationChecked": true, "note": "Administration check RUN, not assumed. NCT00948818 was opened and read on 2026-08-02: intervention type DRUG ('Linaclotide 290 micrograms' and 'Matching placebo'), Phase 3, allocation RANDOMIZED, masking QUADRUPLE, enrolment 803 ACTUAL, lead sponsor Forest Laboratories, status COMPLETED with an ACTUAL completion date of August 2010 and results posted. Linaclotide was ADMINISTERED to humans; it was not measured as an endogenous biomarker, which is the trap that reduces MOTS-c and TB-500 from an apparent five human RCTs to an actual zero. The companion pivotal trial NCT00938717 was checked the same way: Phase 3, randomised, quadruple-masked, placebo-controlled, 805 ACTUAL enrolment, lead sponsor Ironwood Pharmaceuticals, COMPLETED September 2010. Both are named in section 14.1 of the current FDA-approved label as Trials 1 and 2, which is the independent corroboration. SCOPE, and it is narrower than the badge. This tier attaches to the approved indications in the approved oral product, and it is strongest for adults. Two limits are visible in the label itself. First, effect sizes are modest: in Trials 1 and 2 the combined responder rates were 12% versus 5% placebo and 13% versus 3% placebo, recorded below with FDA's own confidence intervals. 'Proven in humans' means efficacy was established in adequate and well-controlled trials, not that most patients respond. Second, the paediatric IBS-C indication does NOT rest on a placebo-controlled result — see the finding below on Trial 8, which had no placebo arm and reports a single-arm responder rate.", "source": { "url": "https://clinicaltrials.gov/study/NCT00948818", "title": "A Phase III, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Trial of Linaclotide Administered Orally for 12 Weeks Followed by a 4-Week Randomized Withdrawal Period in Patients With Irritable Bowel Syndrome With Constipation", "publisher": "ClinicalTrials.gov", "date": "2013-01-30", "quote": "A Phase III, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Trial of Linaclotide Administered Orally … in Patients With Irritable Bowel Syndrome With Constipation" }, "verifiedAt": "2026-08-02" }, "fdaApproval": { "applicationNumber": "NDA 202811", "brandName": "Linzess", "approvedIndication": "LINZESS is indicated for the treatment of: • irritable bowel syndrome with constipation (IBS-C) in adults and pediatric patients 7 years of age and older • chronic idiopathic constipation (CIC) in adults • functional constipation (FC) in pediatric patients 2 years of age and older", "discontinued": false, "source": { "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2026/202811s023lbl.pdf", "title": "LINZESS (linaclotide) capsules — Highlights of Prescribing Information (NDA 202811, s023)", "publisher": "FDA", "date": "2026-05-22", "quote": "LINZESS is indicated for the treatment of: • irritable bowel syndrome with constipation (IBS-C) in adults and pediatric patients 7 years of age and older • chronic idiopathic constipation (CIC) in adults • functional constipation (FC) in pediatric patients 2 years of age and older" }, "verifiedAt": "2026-08-02" }, "fdaFindings": [ { "finding": "The 2012 original approval label for LINZESS was for adults only, and its boxed warning was headed 'WARNING: PEDIATRIC RISK'. That label contraindicated LINZESS in pediatric patients up to 6 years of age and told prescribers to avoid use in pediatric patients 6 through 17 years of age.", "note": "Recorded because the current label cannot show this and the movement is the story. In 2012 FDA's boxed warning told prescribers to AVOID the drug in every paediatric patient and contraindicated it below six years. Fourteen years later the same application is approved from two years of age for functional constipation and from seven for IBS-C, and the boxed warning has been re-scoped to patients under two. Two readings to avoid. This is not FDA relaxing a safety finding — the underlying nonclinical finding (deaths in neonatal mice from dehydration) is still in the current label and still drives the contraindication. It is the age boundary moving as paediatric trials were actually run. And it is not a general precedent: nothing here transfers to any other peptide, because what changed the label was adequate and well-controlled paediatric trials in an approved product, of which the research-chemical market has none.", "source": { "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/202811s000lbl.pdf", "title": "LINZESS (linaclotide) capsules — original approval label (NDA 202811, s000)", "publisher": "FDA", "date": "2012-08-31", "quote": "WARNING: PEDIATRIC RISK … LINZESS is contraindicated in pediatric patients up to 6 years of age. Avoid use of LINZESS in pediatric patients 6 through 17 years of age. Linaclotide caused deaths in young juvenile mice … LINZESS is a guanylate cyclase-C agonist indicated in adults for treatment of: • Irritable bowel syndrome with constipation (IBS-C) … • Chronic idiopathic constipation (CIC)" }, "verifiedAt": "2026-08-02" }, { "finding": "FDA approved LINZESS to treat functional constipation in pediatric patients 6 to 17 years of age on 12 June 2023, stating that it was the first treatment for pediatric functional constipation. The application received priority review.", "note": "FDA's own announcement, and the cleanest available statement of first-in-indication status for this drug. FDA describes the supporting evidence precisely: efficacy was established in a 12-week double-blind, placebo-controlled, randomised, multicentre trial (Trial 7, NCT04026113) 'and supported by efficacy data from adequate and well-controlled trials in adults with chronic idiopathic constipation'. Note the structure — a placebo-controlled paediatric trial PLUS extrapolation from adults, not extrapolation alone. The age range in this 2023 announcement (6 to 17) is not the current indication; the floor moved to 2 years on 2026-05-21 and the ceiling was removed. Cite this document for what happened in 2023, not for what the label says today.", "source": { "url": "https://www.fda.gov/drugs/news-events-human-drugs/fda-approves-first-treatment-pediatric-functional-constipation", "title": "FDA approves first treatment for pediatric functional constipation", "publisher": "FDA", "date": "2023-06-12", "quote": "FDA has approved Linzess (linaclotide) capsules to treat functional constipation in pediatric patients 6 to 17 years of age. Linzess is the first treatment for pediatric functional constipation." }, "verifiedAt": "2026-08-02" }, { "finding": "The IBS-C indication was extended into paediatrics by supplement 22, approved 2025-11-04, whose label reads 'Irritable bowel syndrome with constipation (IBS-C) in adults and pediatric patients 7 years of age and older' and, at that revision, 'Functional constipation (FC) in pediatric patients 6 years of age and older'.", "note": "The middle step, recorded against its own document because neither the 2023 announcement nor the current label shows it. Verified by fetching supplement 21's label (approved 2023-06-12) and supplement 22's side by side on 2026-08-02: s021 reads 'Irritable bowel syndrome with constipation (IBS-C) in adults' and 'Functional constipation (FC) in pediatric patients 6 to 17 years of age'; s022 adds paediatric IBS-C from 7 years and opens the FC range upward by replacing '6 to 17 years' with '6 years of age and older'. So the hint that this drug is an adult IBS-C product is a description of the 2012 label, not of the current one, and the paediatric IBS-C indication is roughly nine months old.", "source": { "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/202811s022lbl.pdf", "title": "LINZESS (linaclotide) capsules — approval label (NDA 202811, s022)", "publisher": "FDA", "date": "2025-11-05", "quote": "LINZESS is a guanylate cyclase-C agonist indicated for treatment of: • Irritable bowel syndrome with constipation (IBS-C) in adults and pediatric patients 7 years of age and older. (1) • Chronic idiopathic constipation (CIC) in adults. (1) • Functional constipation (FC) in pediatric patients 6 years of age and older. (1)" }, "verifiedAt": "2026-08-02" }, { "finding": "The efficacy analysis supporting the pediatric IBS-C indication had no placebo comparator. In Trial 8 (NCT04026113), 108 patients were randomised to LINZESS or to a higher than recommended dosage of LINZESS, and 53 patients were evaluated for efficacy. The label reports a single-arm combined responder rate of 30% (95% CI 18% to 44%) with no placebo column and no treatment difference. FDA states the indication is supported by evidence from adequate and well-controlled studies in adults and in pediatric patients 7 to 17 years of age.", "note": "The most important qualification on this record, and it is invisible unless you open sections 14.2 and 8.4 of the label. The paediatric IBS-C trial was not linaclotide versus placebo — both arms received linaclotide, and the comparison was against a higher than recommended dosage, which the label reports 'did not demonstrate additional treatment benefit'. Table 6 of the label accordingly shows one column. A 30% responder rate with no control arm is not a treatment effect; the label does not present it as one, and the indication rests on extrapolation from the adult placebo-controlled trials. Contrast the paediatric FUNCTIONAL CONSTIPATION trials, which WERE placebo-controlled: Trial 7 (ages 6 to 17, N=328) reported a treatment difference of 1.3 spontaneous bowel movements per week (95% CI 0.7 to 1.8), and Trial 9 (NCT05652205, ages 2 to 5, N=62 on LINZESS and 61 on placebo) reported 0.7 (95% CI 0.03 to 1.31) — an interval whose lower bound is 0.03, which clears zero by almost nothing. Same drug, same label, three very different evidentiary footings.", "source": { "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2026/202811s023lbl.pdf", "title": "LINZESS (linaclotide) capsules — Highlights of Prescribing Information (NDA 202811, s023)", "publisher": "FDA", "date": "2026-05-22", "quote": "A total of 108 patients were randomized to receive treatment with LINZESS … or a higher than recommended dosage of LINZESS. … A total of 53 patients who received LINZESS … were evaluated for efficacy. … The safety and effectiveness of LINZESS for the treatment of IBS-C have been established in pediatric patients 7 years of age and older. Use of LINZESS for this indication is supported by evidence from adequate and well-controlled studies in adults and pediatric patients 7 to 17 years of age." }, "verifiedAt": "2026-08-02" }, { "finding": "In the two pivotal placebo-controlled trials in adults with IBS-C, the label reports combined responder rates (abdominal pain and complete spontaneous bowel movement responder, for at least 9 out of 12 weeks) of 12% on LINZESS versus 5% on placebo in Trial 1, a difference of 7% (95% CI 3.2% to 10.9%), and 13% versus 3% in Trial 2, a difference of 10% (95% CI 6.1% to 13.4%).", "note": "Recorded verbatim from Tables 3 and 4 because 'FDA-approved' and 'works for most people' are different claims and the second one is not on this label. On the stricter primary endpoint roughly one in eight patients met the combined responder definition, against one in twenty on placebo. On the looser 6-out-of-12-week endpoint the same trials report 34% versus 21% and 34% versus 14%. The separation is real, statistically significant and replicated across two trials — that is what earns the tier — and it is also modest in absolute terms. Both facts are in the same table. Anyone quoting one without the other is quoting half a document.", "source": { "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2026/202811s023lbl.pdf", "title": "LINZESS (linaclotide) capsules — Highlights of Prescribing Information (NDA 202811, s023)", "publisher": "FDA", "date": "2026-05-22", "quote": "In both trials, the proportion of patients who were responders to LINZESS … was statistically significantly higher than with placebo." }, "verifiedAt": "2026-08-02" }, { "finding": "Linaclotide appears in none of Categories 1, 2 or 3 of FDA's 503A bulk drug substances list updated 2026-05-14.", "note": "Recorded to close a misreading, not to assert a status. Verified by fetching the document with a browser user-agent and text-extracting it on 2026-08-02: zero hits for 'linaclotide' and zero for 'Linzess' across all seven pages. This absence means something entirely different from BPC-157's absence. BPC-157 was nominated and left Category 2 when the nominators withdrew. Linaclotide was never in this system at all — the 503A bulks nomination route exists for substances that are not already components of approved drug products, and linaclotide is the active ingredient of one. The bulks list can establish absence and nothing more; it cannot distinguish 'withdrawn' from 'never nominated' from 'approved drug, never on the nomination track'. This record therefore carries no 503A status badge at all, because inventing one would assert a fact about a proceeding linaclotide was never part of.", "source": { "url": "https://www.fda.gov/media/94155/download", "title": "Bulk Drug Substances Nominated for Use in Compounding Under Section 503A of the Federal Food, Drug, and Cosmetic Act", "publisher": "FDA", "date": "2026-05-14" }, "verifiedAt": "2026-08-02" }, { "finding": "Drugs@FDA lists three abbreviated new drug applications for linaclotide. Two were approved — Mylan's ANDA 209564 on 2021-02-09 and Aurobindo's ANDA 209611 on 2023-02-07 — and every product under both is marked Discontinued. The third, Actavis Labs FL's ANDA 211255, holds a tentative approval dated 2026-05-19 and has no marketing status.", "note": "A generic being approved and a generic being available are different facts, and the gap between them is visible in the database. Both approved linaclotide ANDAs show every product Discontinued, and the third application is only TENTATIVELY approved, which in FDA's own scheme means the application meets the approval requirements but cannot be marketed yet. This record makes no claim about WHY — patent and exclusivity positions are not in this dataset, and the site does not guess at them. What is checkable is the state: as of the 2026-07-31 Drugs@FDA extract, the only linaclotide products with a Prescription marketing status are the three brand LINZESS capsules under NDA 202811.", "source": { "url": "https://api.fda.gov/drug/drugsfda.json?search=products.active_ingredients.name:\"LINACLOTIDE\"&limit=10", "title": "Drugs@FDA — applications containing linaclotide (openFDA drug/drugsfda)", "publisher": "FDA", "date": "2026-07-31" }, "verifiedAt": "2026-08-02" } ], "safetySignals": [ { "signal": "Boxed warning — risk of serious dehydration in pediatric patients less than 2 years of age. LINZESS is contraindicated in patients less than 2 years of age; in neonatal mice, linaclotide caused deaths due to dehydration.", "note": "FDA's highest-level warning, and it sits on a drug that is simultaneously approved for two-year-olds. Those two facts are not in tension — they meet exactly at the same age boundary. The contraindication floor is 'less than 2 years' and the youngest approved indication is 'pediatric patients 2 years of age and older'. There is no gap and no overlap. The label's expanded section 5.1 gives the mechanism: in neonatal mice, 'linaclotide increased fluid secretion as a consequence of age-dependent elevated GC-C agonism which was associated with increased mortality within the first 24 hours due to dehydration'. FDA adds that a clinical GC-C ontogeny study in 99 children found insufficient data on GC-C intestinal expression to assess the risk in children under two — so the boundary is drawn at the edge of what was measured, not at a demonstrated safe threshold.", "source": { "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2026/202811s023lbl.pdf", "title": "LINZESS (linaclotide) capsules — Highlights of Prescribing Information (NDA 202811, s023)", "publisher": "FDA", "date": "2026-05-22", "quote": "WARNING: RISK OF SERIOUS DEHYDRATION IN PEDIATRIC PATIENTS LESS THAN 2 YEARS OF AGE … LINZESS is contraindicated in patients less than 2 years of age; in neonatal mice, linaclotide caused deaths due to dehydration." }, "verifiedAt": "2026-08-02" }, { "signal": "Diarrhea was the most common adverse reaction in the pooled pivotal placebo-controlled IBS-C trials: 20% of LINZESS-treated patients reported diarrhea versus 3% of placebo-treated patients, severe diarrhea was reported in 2% versus less than 1%, and 5% of LINZESS-treated patients discontinued due to diarrhea versus less than 1% on placebo.", "note": "Worth stating in the label's own numbers because the adverse reaction here is a stronger signal than the efficacy one. In the same pivotal trials the combined responder difference was 7 to 10 percentage points; the diarrhea difference was 17 percentage points. The label also records that in open-label long-term trials 29% of patients had their dose reduced or suspended because of adverse reactions, the majority diarrhea or other gastrointestinal reactions, and that most reported cases of diarrhea started within the first two weeks.", "source": { "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2026/202811s023lbl.pdf", "title": "LINZESS (linaclotide) capsules — Highlights of Prescribing Information (NDA 202811, s023)", "publisher": "FDA", "date": "2026-05-22", "quote": "In these trials, 20% of LINZESS-treated patients reported diarrhea compared to 3% of placebo-treated patients. Severe diarrhea was reported in 2% of the LINZESS-treated patients versus less than 1% of the placebo-treated patients, and 5% of LINZESS-treated patients discontinued due to diarrhea vs less than 1% of placebo-treated patients." }, "verifiedAt": "2026-08-02" }, { "signal": "In post-marketing experience, severe diarrhea associated with dizziness, syncope, hypotension and electrolyte abnormalities (hypokalemia and hyponatremia) requiring hospitalization or intravenous fluid administration has been reported in patients treated with LINZESS.", "note": "The consequence chain the trial incidence table does not show. Diarrhea is the labelled adverse reaction; the reported harm is what follows it — volume and electrolyte loss severe enough for admission or intravenous fluids. This is also the same physiological pathway as the boxed warning, scaled to a different population: fluid secretion driven by GC-C agonism, which kills neonatal mice and dehydrates adults. One mechanism, two warnings.", "source": { "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2026/202811s023lbl.pdf", "title": "LINZESS (linaclotide) capsules — Highlights of Prescribing Information (NDA 202811, s023)", "publisher": "FDA", "date": "2026-05-22", "quote": "In post-marketing experience, severe diarrhea associated with dizziness, syncope, hypotension and electrolyte abnormalities (hypokalemia and hyponatremia) requiring hospitalization or intravenous fluid administration have been reported in patients treated with LINZESS." }, "verifiedAt": "2026-08-02" }, { "signal": "LINZESS is contraindicated in patients with known or suspected mechanical gastrointestinal obstruction, in addition to the contraindication in patients less than 2 years of age.", "note": "Recorded because it is the contraindication that survives from the 2012 label unchanged while the paediatric one moved, and because it is a screening question rather than a monitoring one. It cannot be answered by the patient alone.", "source": { "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2026/202811s023lbl.pdf", "title": "LINZESS (linaclotide) capsules — Highlights of Prescribing Information (NDA 202811, s023)", "publisher": "FDA", "date": "2026-05-22", "quote": "LINZESS is contraindicated in: Patients less than 2 years of age due to the risk of serious dehydration … Patients with known or suspected mechanical gastrointestinal obstruction." }, "verifiedAt": "2026-08-02" } ], "faqs": [ { "question": "Is Linzess (linaclotide) FDA-approved?", "answer": "Yes. Linaclotide is approved by FDA under NDA 202811 and marketed as LINZESS capsules, with an initial U.S. approval in 2012. The current labeling, approved 21 May 2026, states that 'LINZESS is indicated for the treatment of: • irritable bowel syndrome with constipation (IBS-C) in adults and pediatric patients 7 years of age and older • chronic idiopathic constipation (CIC) in adults • functional constipation (FC) in pediatric patients 2 years of age and older'. Read the age floors, because they differ by indication and a summary flattens them: chronic idiopathic constipation is an adults-only indication, IBS-C reaches down to 7 years, and functional constipation reaches down to 2 years. Approval attaches to the approved oral capsule product for these uses and does not travel to anything else.", "source": { "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2026/202811s023lbl.pdf", "title": "LINZESS (linaclotide) capsules — Highlights of Prescribing Information (NDA 202811, s023)", "publisher": "FDA", "date": "2026-05-22", "quote": "LINZESS is indicated for the treatment of: • irritable bowel syndrome with constipation (IBS-C) in adults and pediatric patients 7 years of age and older • chronic idiopathic constipation (CIC) in adults • functional constipation (FC) in pediatric patients 2 years of age and older" }, "verifiedAt": "2026-08-02" }, { "question": "Why does Linzess have a boxed warning if it is approved for young children?", "answer": "Because the boxed warning and the youngest approved indication meet at the same age line rather than overlapping. FDA's boxed warning reads: 'LINZESS is contraindicated in patients less than 2 years of age; in neonatal mice, linaclotide caused deaths due to dehydration.' The youngest approved indication is functional constipation in pediatric patients 2 years of age and older. So the warning covers everyone below two and the approval starts at two — no gap, no contradiction. The label's fuller explanation is that in neonatal mice linaclotide 'increased fluid secretion as a consequence of age-dependent elevated GC-C agonism which was associated with increased mortality within the first 24 hours due to dehydration', and that a clinical study measuring GC-C expression in 99 children found insufficient data to assess that risk in children under two. The boundary is drawn where the measurement stops, not at a demonstrated safe threshold.", "source": { "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2026/202811s023lbl.pdf", "title": "LINZESS (linaclotide) capsules — Highlights of Prescribing Information (NDA 202811, s023)", "publisher": "FDA", "date": "2026-05-22", "quote": "WARNING: RISK OF SERIOUS DEHYDRATION IN PEDIATRIC PATIENTS LESS THAN 2 YEARS OF AGE … LINZESS is contraindicated in patients less than 2 years of age; in neonatal mice, linaclotide caused deaths due to dehydration." }, "verifiedAt": "2026-08-02" }, { "question": "When was Linzess approved for children?", "answer": "In three separate steps, and the current label shows only the endpoint. FDA approved LINZESS for functional constipation in pediatric patients 6 to 17 years of age on 12 June 2023, announcing that 'Linzess is the first treatment for pediatric functional constipation' and that the application received priority review. FDA then approved supplement 22 on 4 November 2025, whose label extended the IBS-C indication to 'adults and pediatric patients 7 years of age and older' while stating functional constipation for 'pediatric patients 6 years of age and older'. Supplement 23, approved 21 May 2026, lowered the functional-constipation floor again, to 'pediatric patients 2 years of age and older'. None of this changed the adults-only chronic idiopathic constipation indication.", "source": { "url": "https://www.fda.gov/drugs/news-events-human-drugs/fda-approves-first-treatment-pediatric-functional-constipation", "title": "FDA approves first treatment for pediatric functional constipation", "publisher": "FDA", "date": "2023-06-12", "quote": "FDA has approved Linzess (linaclotide) capsules to treat functional constipation in pediatric patients 6 to 17 years of age. Linzess is the first treatment for pediatric functional constipation." }, "verifiedAt": "2026-08-02" }, { "question": "How well did linaclotide work in the trials FDA approved it on?", "answer": "It separated from placebo consistently, and by a modest amount. In the two pivotal double-blind, placebo-controlled trials in adults with IBS-C (Trials 1 and 2, NCT00948818 and NCT00938717), the label reports combined responder rates — patients meeting both the abdominal pain and the complete-spontaneous-bowel-movement criteria for at least 9 of the first 12 weeks — of 12% on LINZESS versus 5% on placebo in Trial 1, a difference of 7% (95% CI 3.2% to 10.9%), and 13% versus 3% in Trial 2, a difference of 10% (95% CI 6.1% to 13.4%). FDA's own summary is that 'In both trials, the proportion of patients who were responders to LINZESS … was statistically significantly higher than with placebo.' On a looser responder definition (at least 6 of 12 weeks) the same trials report 34% versus 21% and 34% versus 14%. For comparison, the same label reports diarrhea in 20% of LINZESS-treated patients versus 3% on placebo. Statistically significant and replicated is what an approval requires; it is not the same claim as most patients responding.", "source": { "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2026/202811s023lbl.pdf", "title": "LINZESS (linaclotide) capsules — Highlights of Prescribing Information (NDA 202811, s023)", "publisher": "FDA", "date": "2026-05-22", "quote": "In both trials, the proportion of patients who were responders to LINZESS … was statistically significantly higher than with placebo." }, "verifiedAt": "2026-08-02" }, { "question": "Is there a generic version of Linzess?", "answer": "Approved, but not marketed. Drugs@FDA lists three abbreviated new drug applications for linaclotide: Mylan's ANDA 209564, approved 9 February 2021, and Aurobindo Pharma's ANDA 209611, approved 7 February 2023 — every product under both is marked Discontinued — plus Actavis Labs FL's ANDA 211255, which holds a tentative approval dated 19 May 2026 and has no marketing status. As of the 31 July 2026 Drugs@FDA extract, the only linaclotide products carrying a Prescription marketing status are the three brand LINZESS capsules under NDA 202811. This record makes no claim about why the generics are not on the market; patent and exclusivity positions are not in this dataset.", "source": { "url": "https://api.fda.gov/drug/drugsfda.json?search=products.active_ingredients.name:\"LINACLOTIDE\"&limit=10", "title": "Drugs@FDA — applications containing linaclotide (openFDA drug/drugsfda)", "publisher": "FDA", "date": "2026-07-31" }, "verifiedAt": "2026-08-02" }, { "question": "Is linaclotide a peptide you inject?", "answer": "No. Linaclotide is a 14-amino acid peptide, but the approved product is an oral capsule and the drug is not meant to reach the bloodstream at all. FDA's label states that 'LINZESS is minimally absorbed with negligible systemic availability following oral administration' and that plasma concentrations of linaclotide and its active metabolite are below the limit of quantitation, so standard pharmacokinetic parameters such as AUC, Cmax and half-life cannot be calculated for it. The label describes linaclotide as structurally related to human guanylin and uroguanylin, binding guanylate cyclase-C and acting locally on the luminal surface of the intestinal epithelium, then being proteolytically degraded within the intestinal lumen. It is a useful counterexample to two assumptions this category runs on — that a peptide drug must be injected, and that oral peptides do not get approved.", "source": { "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2026/202811s023lbl.pdf", "title": "LINZESS (linaclotide) capsules — Highlights of Prescribing Information (NDA 202811, s023)", "publisher": "FDA", "date": "2026-05-22", "quote": "LINZESS is minimally absorbed with negligible systemic availability following oral administration. Concentrations of linaclotide and its active metabolite in plasma are below the limit of quantitation … Therefore, standard pharmacokinetic parameters such as area under the curve (AUC), maximum concentration (C max ), and half-life (t ½ ) cannot be calculated." }, "verifiedAt": "2026-08-02" }, { "question": "Can a compounding pharmacy make linaclotide?", "answer": "This site cannot answer that from the document it would normally use, and says so rather than guessing. Linaclotide appears in none of Categories 1, 2 or 3 of FDA's 503A bulk drug substances list updated 14 May 2026 — verified by fetching and text-extracting that document on 2 August 2026, which returned zero hits for 'linaclotide' and zero for 'Linzess'. But that absence does not mean for linaclotide what it means for BPC-157. The 503A bulks list is the route for substances that are not already components of approved drug products, and linaclotide is the active ingredient of one: LINZESS capsules under NDA 202811. So the list establishes only that linaclotide was never in that nomination process, which is a different fact from whether a pharmacy may compound with it. Anyone who needs the compounding answer should get it from the statute and their state board, not from this list.", "source": { "url": "https://www.fda.gov/media/94155/download", "title": "Bulk Drug Substances Nominated for Use in Compounding Under Section 503A of the Federal Food, Drug, and Cosmetic Act", "publisher": "FDA", "date": "2026-05-14" }, "verifiedAt": "2026-08-02" } ] }, { "slug": "liraglutide", "name": "Liraglutide", "aliases": [ "Victoza", "Saxenda", "NN2211", "Xultophy 100/3.6" ], "url": "https://peptides101.com/compounds/liraglutide", "moleculeNote": "A glucagon-like peptide-1 (GLP-1) receptor agonist. The disambiguation that matters here is not the molecule — it is that ONE molecule carries THREE different regulatory identities under the same generic name. Victoza (NDA 022341) and Saxenda (NDA 206321) are the same active ingredient at the same concentration from the same sponsor, and their approved indications do not overlap at all: one is a type 2 diabetes and cardiovascular drug, the other a weight-management drug. Liraglutide is also, unlike semaglutide and tirzepatide, available as approved generics — FDA's own notice names a generic application alongside the two brands — and it is a component of a fixed-combination product with insulin degludec (Xultophy 100/3.6, BLA 208583). 'Liraglutide' therefore does not identify a product, an indication, or a label.", "quickAnswer": "Liraglutide is the active ingredient in two FDA-approved Novo Nordisk prescription products whose approved indications do not overlap — Victoza (NDA 022341), indicated as an adjunct to diet and exercise to improve glycemic control in adults and pediatric patients aged 10 years and older with type 2 diabetes mellitus and to reduce the risk of major adverse cardiovascular events in adults with type 2 diabetes and established cardiovascular disease, and Saxenda (NDA 206321), indicated with a reduced calorie diet and increased physical activity to reduce excess body weight and maintain weight reduction long term in adults and pediatric patients aged 12 years and older with obesity and body weight greater than 60 kg and in adults with overweight and at least one weight-related comorbid condition. Both labels carry a boxed warning for risk of thyroid C-cell tumors, and liraglutide is additionally approved as generic products under eleven ANDAs. Liraglutide differs from the other GLP-1 drugs on one point that is widely reported wrongly: FDA-approved liraglutide injection remains on FDA's drug shortage list, listed since 18 July 2023 and reverified by FDA on 13 July 2026, whereas FDA has stated that 'Tirzepatide and semaglutide do not currently appear on the 503B bulks list or on FDA's drug shortage list.' FDA nonetheless proposed on 1 May 2026 not to add liraglutide to the 503B Bulks List, tentatively finding no attribute of the approved liraglutide products that makes them medically unsuitable — a tentative proposal on which comments closed 30 June 2026, and one in which FDA stated it need not decide the second part of its analysis. Liraglutide appears in none of the three categories of FDA's separate 503A bulk drug substances list updated 14 May 2026.", "fdaStatus": { "value": "approved", "note": "FDA-approved. Cross-checked against Drugs@FDA on 2026-08-02: NDA 022341 (Victoza, Novo Nordisk Inc) and NDA 206321 (Saxenda, Novo) both carry marketing status 'Prescription' — neither is discontinued. Approval is always for a specific indication and population, and here there are two approvals with non-overlapping ones; see the approval record below.", "source": { "url": "https://www.govinfo.gov/content/pkg/FR-2026-05-01/html/2026-08552.htm", "title": "List of Bulk Drug Substances for Which There Is a Clinical Need Under Section 503B of the Federal Food, Drug, and Cosmetic Act (Docket No. FDA-2018-N-3240)", "publisher": "Federal Register / FDA", "date": "2026-05-01", "quote": "Liraglutide is an active ingredient in FDA-approved drug products: 18 mg/3 mL (6 mg/mL) solution for SC injection (Saxenda, NDA 206321); 18 mg/3 mL (6 mg/mL) solution for SC injection (Victoza, NDA 022341); and 18 mg/3 mL (6 mg/mL) solution for SC injection (liraglutide 18 mg/3 mL, e.g., ANDA 215503). Each FDA-approved liraglutide product contains propylene glycol." }, "verifiedAt": "2026-08-02" }, "compoundingStatus": null, "evidence": { "tier": "proven-in-humans", "humanAdministrationChecked": true, "note": "ADMINISTRATION CHECK RUN, NOT ASSUMED. Two pivotal registrations were opened individually on 2026-08-02 and read field by field. LEADER (NCT01179048): intervention type DRUG, liraglutide injected subcutaneously versus placebo, Phase 3, allocation RANDOMIZED, double-masked, enrolment 9,341 ACTUAL, lead sponsor Novo Nordisk A/S, status COMPLETED (primary completion and completion both 2015-12-17 ACTUAL, the date carried in the source above), hasResults true. SCALE Obesity and Prediabetes (NCT01272219): intervention type DRUG, liraglutide injected subcutaneously versus placebo, Phase 3, RANDOMIZED, double-masked, enrolment 3,731 ACTUAL, Novo Nordisk A/S, COMPLETED 2015-03-02 ACTUAL, hasResults true. In both, liraglutide was ADMINISTERED to human participants — it was not measured as an endogenous biomarker, which is the trap that reduces MOTS-c and TB-500 from an apparent five human RCTs to an actual zero. INDEPENDENTLY CORROBORATED AGAINST THE LABELS, which is why these two registrations rather than any others: section 14 of the Victoza label names 'a cardiovascular outcomes trial (LEADER trial)', and section 14.1 of the Saxenda label describes 'three 56-week, randomized, double-blind, placebo-controlled trials' whose Study 1 'enrolled 3,731 patients' — the same figure the SCALE registration reports as actual enrolment. SCOPE, and it is narrow. The tier attaches to the two approved products and their approved indications. It does not transfer to compounded liraglutide, to liraglutide from an unapproved source, or to any use outside those labels. Both trials were sponsored by the manufacturer. Neither tested a compounded preparation. NOT CHECKED, and stated rather than implied: no attempt was made here to verify the generic applications' bioequivalence data, which is a different evidentiary question from the one this tier answers.", "source": { "url": "https://clinicaltrials.gov/study/NCT01179048", "title": "LEADER — A Long-term, Multi-centre, International, Randomised Double-blind, Placebo-controlled Trial to Determine Liraglutide Effects on Cardiovascular Events", "publisher": "ClinicalTrials.gov", "date": "2015-12-17" }, "verifiedAt": "2026-08-02" }, "fdaApproval": { "applicationNumber": "NDA 022341 (Victoza); NDA 206321 (Saxenda)", "brandName": "Victoza, Saxenda", "approvedIndication": "VICTOZA (NDA 022341), verbatim: 'VICTOZA is indicated: • as an adjunct to diet and exercise to improve glycemic control in adults and pediatric patients aged 10 years and older with type 2 diabetes mellitus, • to reduce the risk of major adverse cardiovascular events (cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke) in adults with type 2 diabetes mellitus and established cardiovascular disease. Limitations of Use: VICTOZA contains liraglutide. Coadministration with other liraglutide-containing products is not recommended.' — SAXENDA (NDA 206321), verbatim: 'SAXENDA is indicated in combination with a reduced calorie diet and increased physical activity to reduce excess body weight and maintain weight reduction long term in: • Adults and pediatric patients aged 12 years and older with body weight greater than 60 kg and obesity. • Adults with overweight in the presence of at least one weight-related comorbid condition.'", "discontinued": false, "source": { "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/022341s046lbl.pdf", "title": "VICTOZA (liraglutide) injection — Highlights of Prescribing Information", "publisher": "FDA", "date": "2025-10-14" }, "verifiedAt": "2026-08-02" }, "fdaFindings": [ { "finding": "FDA has proposed not to include liraglutide on the 503B Bulks List, alongside semaglutide and tirzepatide, having tentatively found no basis to conclude there is a clinical need for an outsourcing facility to compound using it.", "note": "Two distinctions the coverage collapses. This is section 503B (outsourcing facilities), NOT the 503A bulks list that BPC-157 and the consumer peptides sit against — different statutory provision, different list, different test. And it is a TENTATIVE finding in a proposed notice, not a final determination; comments were due 2026-06-30. What FDA actually evaluated is narrow: whether the nomination identified an attribute of the approved liraglutide products making them medically unsuitable for identified patients.", "source": { "url": "https://www.govinfo.gov/content/pkg/FR-2026-05-01/html/2026-08552.htm", "title": "List of Bulk Drug Substances for Which There Is a Clinical Need Under Section 503B of the Federal Food, Drug, and Cosmetic Act (Docket No. FDA-2018-N-3240)", "publisher": "Federal Register / FDA", "date": "2026-05-01", "quote": "FDA tentatively finds no basis to conclude that there is a clinical need for an outsourcing facility to compound using the following bulk drug substances: semaglutide, tirzepatide, and liraglutide. Therefore, we propose not to include these bulk drug substances on the 503B Bulks List." }, "verifiedAt": "2026-08-02" }, { "finding": "On liraglutide specifically, FDA tentatively found no basis to conclude that there is an attribute of the FDA-approved liraglutide products that makes them medically unsuitable to treat certain patients for a condition FDA identified for evaluation.", "note": "Recorded separately from the conclusion above because it is the actual reasoning, and because it must not be re-read as a safety blessing. 'No attribute makes the approved products medically unsuitable' is a finding ABOUT THE APPROVED PRODUCTS being adequate — the approved drug being good enough is the reason compounding was refused. It is not a finding that compounded liraglutide is safe, and it is not a finding that it is unsafe. FDA's stated grounds, in its own sequence: the only compounded strength the nominator identified is the same as the approved products'; the nominator never identified which inactive ingredients patients were said to be intolerant of; the propylene-glycol argument was not supported (see below); and the container-closure argument was held inapplicable to this stage of the analysis.", "source": { "url": "https://www.govinfo.gov/content/pkg/FR-2026-05-01/html/2026-08552.htm", "title": "List of Bulk Drug Substances for Which There Is a Clinical Need Under Section 503B of the Federal Food, Drug, and Cosmetic Act (Docket No. FDA-2018-N-3240)", "publisher": "Federal Register / FDA", "date": "2026-05-01", "quote": "For these reasons, FDA tentatively finds no basis to conclude that there is an attribute of the FDA-approved drug products containing liraglutide that makes them medically unsuitable to treat certain patients for a condition that FDA has identified for evaluation and that the proposed compounded products are intended to address." }, "verifiedAt": "2026-08-02" }, { "finding": "FDA stated it has not identified any data or information to suggest that propylene glycol would cause a drug product containing liraglutide to be medically unsuitable, and reported that the single article the nominator submitted did not evaluate liraglutide at all and did not say what it was cited for.", "note": "This is FDA opening a citation and finding it does not say what it was cited for — the same failure this site exists to correct, caught by the regulator, in a filing, against a represented party. The paper is Snitker et al. (2022), and FDA recorded two separate problems with it: it 'did not evaluate liraglutide' — it compared semaglutide formulations — and its authors concluded that 'The injection-site experience with semaglutide D was almost indistinguishable from semaglutide MPI . . . with either product associated with no or very mild injection-site pain', which runs against the preference claim rather than for it. FDA's own FAERS search found numerous reports of injection site reactions in both Victoza and Saxenda users and NO report whose case narrative contained 'propylene'. FDA also noted that injection site reaction is reported in trials of injectable products not formulated with propylene glycol at all, and that all FDA-approved liraglutide injections are already labeled for injection site reactions. The 'PG-free compounded liraglutide' pitch was evaluated and not sustained.", "source": { "url": "https://www.govinfo.gov/content/pkg/FR-2026-05-01/html/2026-08552.htm", "title": "List of Bulk Drug Substances for Which There Is a Clinical Need Under Section 503B of the Federal Food, Drug, and Cosmetic Act (Docket No. FDA-2018-N-3240)", "publisher": "Federal Register / FDA", "date": "2026-05-01", "quote": "FDA has not identified any data or information to suggest that propylene glycol would cause a drug product containing liraglutide to be medically unsuitable. […] The article does not, as the nominator claims, find that \"95% of patients preferred the formulation without propylene glycol.\"" }, "verifiedAt": "2026-08-02" }, { "finding": "FDA did not reach the second part of its clinical-need analysis for liraglutide. Because it found no basis to conclude an attribute of the approved products makes them medically unsuitable, FDA stated it need not decide whether the proposed compounded products must be compounded from a bulk drug substance rather than from an approved drug product.", "note": "Recorded because it is the finding that cuts BOTH ways. FDA's test is sequential and the liraglutide analysis stopped at the threshold, so a whole set of questions was never opened. Elsewhere in the same notice FDA writes that commenters' and the nominator's arguments 'about safety and quality concerns with the nominated bulk drug substances for use in compounding would be addressed in Part 2 of the clinical need analysis, which we do not reach here.' Sellers read that silence as an absence of adverse findings; critics read the proposal as a determination that compounded liraglutide does not work. Neither is what happened. PRECISION NOTE: the sentence in which FDA says it 'did not consider the Part 2 factors, including the available evidence of effectiveness or lack of effectiveness' appears ONCE in this notice, in the SEMAGLUTIDE section. It is not repeated for liraglutide, and this record does not put it in FDA's mouth for liraglutide. What is quoted above is what the liraglutide section actually says.", "source": { "url": "https://www.govinfo.gov/content/pkg/FR-2026-05-01/html/2026-08552.htm", "title": "List of Bulk Drug Substances for Which There Is a Clinical Need Under Section 503B of the Federal Food, Drug, and Cosmetic Act (Docket No. FDA-2018-N-3240)", "publisher": "Federal Register / FDA", "date": "2026-05-01", "quote": "Because there is no basis to conclude that there is an attribute of the FDA-approved drug products containing liraglutide which makes them medically unsuitable to treat certain patients, FDA need not decide whether the proposed drug products containing liraglutide must be compounded from a bulk drug substance rather than using an FDA-approved drug product." }, "verifiedAt": "2026-08-02" }, { "finding": "FDA-approved liraglutide injection remains on FDA's drug shortage list. FDA's shortage database returned ten liraglutide injection records on 2026-08-02, nine of them with status 'Current', initially posted 2023-07-18 and most recently reverified 2026-07-13.", "note": "The reason this record exists, and the reason it has to be read carefully. WHY IT MATTERS STRUCTURALLY: section 503B(a)(2)(A) of the FD&C Act sets out two alternative conditions, and the Federal Register notice above states them — an outsourcing facility may not compound with a bulk drug substance unless '(1) the bulk drug substance appears on a list … identifying bulk drug substances for which there is a clinical need (the 503B Bulks List) or (2) the drug compounded from the bulk drug substance appears on the drug shortage list in effect under section 506E of the FD&C Act … at the time of compounding, distribution, and dispensing.' FDA is proposing to shut door (1) for liraglutide. Door (2) turns on the shortage list, and liraglutide injection is on it. WHAT THIS DOES NOT ESTABLISH, stated plainly because the gap between the two is where this gets misused. It does not establish that any particular compounded liraglutide product is lawful. The shortage condition is one of several conditions in section 503B, it is assessed at the time of compounding, distribution and dispensing rather than once, and it does not touch the separate 'essentially a copy of a commercially available drug product' restriction. Nothing was verified here about any specific compounder, and no FDA statement addressing compounders' reliance on the liraglutide listing was located on 2026-08-02. This entry is a fact about a list. READ THE LIST ENTRIES, NOT THE HEADLINE: of the nine Current records, six report availability 'Available' and three 'Limited Availability'. A drug can remain listed while most presentations are shipping — FDA's own GLP-1 page says that when a status is noted as 'available,' that 'reflects the most current information from the manufacturer but is not an FDA determination that the shortage has been resolved.' The tenth record, a Teva presentation, is 'To Be Discontinued' with reason 'Discontinuation of the manufacture of the drug', posted 2026-05-14 — a discontinuation notice is published in the same database and is not a shortage. COMPARISON, and the limits of it: the same endpoint was queried on 2026-08-02 for semaglutide, tirzepatide, dulaglutide, exenatide, exenatide extended release, lixisenatide, insulin glargine and lixisenatide, insulin degludec and liraglutide, and retatrutide. None returned a record with status 'Current' — semaglutide returned only 'To Be Discontinued' entries for Rybelsus tablets, and the rest returned no matches at all. That is an enumeration of the names queried on one day, not a proof that no other GLP-1 is listed under some name not on that list.", "source": { "url": "https://api.fda.gov/drug/shortages.json?search=generic_name:%22liraglutide%22&limit=20", "title": "FDA Drug Shortages Database — liraglutide injection (openFDA drug/shortages endpoint)", "publisher": "FDA", "date": "2026-08-01" }, "verifiedAt": "2026-08-02" }, { "finding": "FDA has stated that tirzepatide and semaglutide do not currently appear on the 503B bulks list or on FDA's drug shortage list. On the same page, FDA's most recent published GLP-1 shortage status update states that liraglutide injection is in shortage.", "note": "One FDA page, two sentences, opposite answers for three drugs in the same class — which is why the class-wide framing in most 2026 coverage is wrong. DATE DISCIPLINE, because the two halves of the quote are not contemporaneous and joining them without saying so would be sleight of hand. The first sentence sits in the page's current body text; the page's own footer reads 'Content current as of: 04/01/2026'. The second is inside a dated update headed 'Current shortage status of other GLP-1 products (as of February 21, 2025)' — the most recent GLP-1 shortage status list FDA has published on that page, but a snapshot from February 2025, not from 2026. The 2026 currency of the liraglutide listing is carried by the shortage-database entry above, which was reverified by FDA on 2026-07-13, not by this quote. Note also what the February 2025 snapshot shows about drift: it lists dulaglutide injection as in shortage too, and dulaglutide returned no records from the shortage endpoint on 2026-08-02. Shortage listings resolve. This one had not.", "source": { "url": "https://www.fda.gov/drugs/drug-alerts-and-statements/fda-clarifies-policies-compounders-national-glp-1-supply-begins-stabilize", "title": "FDA clarifies policies for compounders as national GLP-1 supply begins to stabilize", "publisher": "FDA", "date": "2026-04-01", "quote": "Tirzepatide and semaglutide do not currently appear on the 503B bulks list or on FDA's drug shortage list. […] Liraglutide injection : In shortage. Manufacturer has reported two presentations are available, and three have limited availability." }, "verifiedAt": "2026-08-02" }, { "finding": "SAXENDA (NDA 206321) is indicated in combination with a reduced calorie diet and increased physical activity to reduce excess body weight and maintain weight reduction long term in adults and pediatric patients aged 12 years and older with body weight greater than 60 kg and obesity, and in adults with overweight in the presence of at least one weight-related comorbid condition.", "note": "Recorded verbatim against its own label because the brand-name gap is the whole point. The weight-management indication belongs to SAXENDA and not to VICTOZA, and the two are the same molecule at the same concentration from the same sponsor. The label's Limitations of Use add that coadministration with other liraglutide-containing products or with any other GLP-1 receptor agonist 'is not recommended', and that safety and effectiveness in pediatric patients with type 2 diabetes 'have not been established' — a limitation that surprises people who assume the diabetes approval carries across from Victoza.", "source": { "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2026/206321s025lbl.pdf", "title": "SAXENDA (liraglutide) injection — Highlights of Prescribing Information", "publisher": "FDA", "date": "2026-02-25", "quote": "SAXENDA is indicated in combination with a reduced calorie diet and increased physical activity to reduce excess body weight and maintain weight reduction long term in: Adults and pediatric patients aged 12 years and older with body weight greater than 60 kg and obesity. Adults with overweight in the presence of at least one weight-related comorbid condition." }, "verifiedAt": "2026-08-02" }, { "finding": "Liraglutide appears in none of Categories 1, 2 or 3 of FDA's 503A bulk drug substances list updated 14 May 2026.", "note": "Recorded to close a misreading, not to assert a status. Verified by fetching the PDF with a browser user-agent and extracting its text locally on 2026-08-02: seven pages, header 'Updated May 14, 2026', and zero occurrences of 'liraglutide' anywhere in it. This absence means something different from BPC-157's absence. BPC-157 was nominated for 503A and left Category 2 when the nominators withdrew. Liraglutide was never in the 503A system — a 503A bulks nomination is a route for substances that are not components of an approved drug, and liraglutide is a component of two NDAs and a set of ANDAs. Categorical silence here is neither permission nor a safety finding, and it says nothing about the separate 503B question above.", "source": { "url": "https://www.fda.gov/media/94155/download", "title": "Bulk Drug Substances Nominated for Use in Compounding Under Section 503A of the Federal Food, Drug, and Cosmetic Act", "publisher": "FDA", "date": "2026-05-14" }, "verifiedAt": "2026-08-02" }, { "finding": "Liraglutide is available as FDA-approved generic drug products. Drugs@FDA listed eleven approved liraglutide ANDAs on 2026-08-02, from Biocon, Fresenius Kabi, Sandoz, Teva, Lupin, Orbicular, Hikma, Nanjing King Friend and Mylan Institutional, the earliest approved 2024-12-23.", "note": "The fact that distinguishes liraglutide from semaglutide and tirzepatide, neither of which has an approved generic, and the one the compounding argument has to get past. Scope: 'has generics' is not unique to liraglutide across the GLP-1 class — exenatide has one approved ANDA (ANDA 206697, Amneal), checked on the same endpoint the same day. Eleven is the count that is unusual. Eight of the eleven carry therapeutic equivalence code AP1 (rated against Victoza) and three AP2 (rated against Saxenda); all eleven show marketing status 'Prescription'. FDA's own 503B notice names one of them in the passage quoted under fdaStatus above ('liraglutide 18 mg/3 mL, e.g., ANDA 215503'), so the existence of generics is carried by a second primary document and not by this query alone. Why it matters: an approved generic is a therapeutically equivalent, FDA-reviewed product available from multiple manufacturers. It is also the strongest form of the finding FDA made under Part 1(a) — the approved products are what a compounded product would have to be shown medically unsuitable against, and there are now thirteen approved applications to clear rather than two. COUNTING CAVEAT: 'eleven ANDAs' is a count of applications on one day, from one query. Approved is not the same as launched, and this record has not verified which are actually being marketed.", "source": { "url": "https://api.fda.gov/drug/drugsfda.json?search=products.active_ingredients.name:%22LIRAGLUTIDE%22&limit=30", "title": "Drugs@FDA — drug products containing liraglutide (openFDA drug/drugsfda endpoint)", "publisher": "FDA", "date": "2026-07-31" }, "verifiedAt": "2026-08-02" } ], "safetySignals": [ { "signal": "Boxed warning — risk of thyroid C-cell tumors, on VICTOZA (NDA 022341). The labeling states that liraglutide causes dose-dependent and treatment-duration-dependent thyroid C-cell tumors at clinically relevant exposures in both genders of rats and mice, and that it is unknown whether VICTOZA causes thyroid C-cell tumors, including medullary thyroid carcinoma (MTC), in humans. Contraindicated in patients with a personal or family history of MTC and in patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2).", "note": "FDA's highest-level warning. Read the direction of the evidence precisely, because overstating it is as much an error as omitting it: this is a rodent finding whose human relevance the label says has not been determined, not a demonstrated human cancer risk. The labeling also states that routine monitoring of serum calcitonin or thyroid ultrasound 'is of uncertain value for early detection of MTC' in treated patients — so the protection here is the contraindication screen, which is a question a prescriber asks and a purchaser of an unapproved vial is never asked.", "source": { "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/022341s046lbl.pdf", "title": "VICTOZA (liraglutide) injection — Highlights of Prescribing Information", "publisher": "FDA", "date": "2025-10-14", "quote": "Liraglutide causes dose-dependent and treatment-duration-dependent thyroid C-cell tumors at clinically relevant exposures in both genders of rats and mice. It is unknown whether VICTOZA causes thyroid C-cell tumors, including medullary thyroid carcinoma (MTC), in humans, as the human relevance of liraglutide-induced rodent thyroid C-cell tumors has not been determined" }, "verifiedAt": "2026-08-02" }, { "signal": "Boxed warning — risk of thyroid C-cell tumors, on SAXENDA (NDA 206321) as well. The labeling carries the same warning in the same terms and the same contraindication for personal or family history of MTC and for Multiple Endocrine Neoplasia syndrome type 2.", "note": "Recorded as its own sourced entry rather than folded into the Victoza signal, because this record's argument is that approval attaches to an application and not to a molecule — so 'both products carry it' has to be two documents saying so, not one document and an inference. Worth stating because the weight-management framing invites the assumption that Saxenda is the lighter-touch product. It carries the identical boxed warning and the identical contraindications.", "source": { "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2026/206321s025lbl.pdf", "title": "SAXENDA (liraglutide) injection — Highlights of Prescribing Information", "publisher": "FDA", "date": "2026-02-25", "quote": "Liraglutide causes dose-dependent and treatment-duration-dependent thyroid C-cell tumors at clinically relevant exposures in both genders of rats and mice. It is unknown whether SAXENDA causes thyroid C-cell tumors, including medullary thyroid carcinoma (MTC), in humans, as the human relevance of liraglutide-induced rodent thyroid C-cell tumors has not been determined" }, "verifiedAt": "2026-08-02" }, { "signal": "VICTOZA labeled warnings and precautions include acute pancreatitis, hypoglycemia, acute kidney injury due to volume depletion, severe gastrointestinal adverse reactions, hypersensitivity reactions, acute gallbladder disease, pulmonary aspiration during general anesthesia or deep sedation, and a warning never to share a VICTOZA pen between patients.", "note": "Reproduced from sections 5.2 to 5.9 of the label read on 2026-08-02, because 'well-tolerated' is doing heavy lifting in the marketing. The label's Recent Major Changes list Severe Gastrointestinal Adverse Reactions (5.6) at 10/2025 and Pulmonary Aspiration During General Anesthesia or Deep Sedation (5.9) at 11/2024 — both are recent additions, so older summaries of this label are incomplete rather than merely dated. The pen-sharing warning is specific to the presentation and has no analogue for a vial.", "source": { "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/022341s046lbl.pdf", "title": "VICTOZA (liraglutide) injection — Highlights of Prescribing Information", "publisher": "FDA", "date": "2025-10-14" }, "verifiedAt": "2026-08-02" }, { "signal": "SAXENDA labeled warnings and precautions include acute pancreatitis, acute gallbladder disease, hypoglycemia, heart rate increase, acute kidney injury due to volume depletion, severe gastrointestinal adverse reactions, hypersensitivity reactions including postmarketing reports of anaphylactic reactions and angioedema, and pulmonary aspiration during general anesthesia or deep sedation.", "note": "From the label read on 2026-08-02. Most common adverse reactions reported at an incidence of 5% or greater, per the label: nausea, diarrhea, constipation, vomiting, injection site reactions, headache, hypoglycemia, dyspepsia, fatigue, dizziness, abdominal pain, increased lipase, upper abdominal pain, pyrexia and gastroenteritis. The label states Saxenda is not recommended in patients with severe gastroparesis, and — a point people miss because the trial population did not have diabetes — that hypoglycemia occurred in Saxenda-treated pediatric patients who did not have type 2 diabetes.", "source": { "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2026/206321s025lbl.pdf", "title": "SAXENDA (liraglutide) injection — Highlights of Prescribing Information", "publisher": "FDA", "date": "2026-02-25" }, "verifiedAt": "2026-08-02" }, { "signal": "FDA reported that a search of the FAERS database identified numerous reports associated with liraglutide and injection site reactions, occurring in both Victoza and Saxenda users.", "note": "Recorded with FDA's own limitation attached, because the report count is doing two jobs at once and they point in different directions. FDA cites the reports as evidence that injection site reactions happen with the approved products — and cites the absence of 'propylene' in any narrative as evidence that the excipient is not the identified cause. FDA's stated caveat on FAERS in this notice, verbatim: 'there is no certainty that the reported adverse event was due to the suspect product. FDA does not require that a causal relationship between a product and event be proven, and the report may not always contain enough detail to properly evaluate an event.' 'Numerous' is FDA's word; the notice publishes no count, and this record does not supply one.", "source": { "url": "https://www.govinfo.gov/content/pkg/FR-2026-05-01/html/2026-08552.htm", "title": "List of Bulk Drug Substances for Which There Is a Clinical Need Under Section 503B of the Federal Food, Drug, and Cosmetic Act (Docket No. FDA-2018-N-3240)", "publisher": "Federal Register / FDA", "date": "2026-05-01", "quote": "A search of the FAERS database identified numerous reports associated with liraglutide and injection site reactions occurring in both Victoza and Saxenda users. The search did not retrieve any reports of liraglutide and injection site reactions with a case narrative containing \"propylene.\"" }, "verifiedAt": "2026-08-02" } ], "faqs": [ { "question": "Is liraglutide FDA approved?", "answer": "Yes — liraglutide is FDA-approved, under two separate Novo Nordisk applications with different indications, and as generic products. FDA's own words: 'Liraglutide is an active ingredient in FDA-approved drug products: 18 mg/3 mL (6 mg/mL) solution for SC injection (Saxenda, NDA 206321); 18 mg/3 mL (6 mg/mL) solution for SC injection (Victoza, NDA 022341); and 18 mg/3 mL (6 mg/mL) solution for SC injection (liraglutide 18 mg/3 mL, e.g., ANDA 215503).' Victoza is indicated for glycemic control in adults and pediatric patients aged 10 years and older with type 2 diabetes mellitus and for reducing the risk of major adverse cardiovascular events in adults with type 2 diabetes and established cardiovascular disease; Saxenda is indicated, with a reduced calorie diet and increased physical activity, for reducing excess body weight and maintaining weight reduction long term in named populations. The approval attaches to those applications and not to the molecule — liraglutide sold by anyone who does not hold an approved application is not an approved drug, whatever the vial says.", "source": { "url": "https://www.govinfo.gov/content/pkg/FR-2026-05-01/html/2026-08552.htm", "title": "List of Bulk Drug Substances for Which There Is a Clinical Need Under Section 503B of the Federal Food, Drug, and Cosmetic Act (Docket No. FDA-2018-N-3240)", "publisher": "Federal Register / FDA", "date": "2026-05-01", "quote": "Liraglutide is an active ingredient in FDA-approved drug products: 18 mg/3 mL (6 mg/mL) solution for SC injection (Saxenda, NDA 206321); 18 mg/3 mL (6 mg/mL) solution for SC injection (Victoza, NDA 022341); and 18 mg/3 mL (6 mg/mL) solution for SC injection (liraglutide 18 mg/3 mL, e.g., ANDA 215503)." }, "verifiedAt": "2026-08-02" }, { "question": "Is Victoza approved for weight loss?", "answer": "No. Both indications in the FDA-approved labeling for Victoza (liraglutide injection, NDA 022341) are confined to type 2 diabetes mellitus: improving glycemic control as an adjunct to diet and exercise in adults and pediatric patients aged 10 years and older with type 2 diabetes, and reducing the risk of major adverse cardiovascular events in adults with type 2 diabetes and established cardiovascular disease. Weight loss is not among them. The liraglutide product that does carry a weight indication is Saxenda (NDA 206321) — the same molecule at the same concentration from the same sponsor, under a different application with different trials behind it. The non-interchangeability runs both ways: Saxenda carries no type 2 diabetes indication, and its label states that its safety and effectiveness in pediatric patients with type 2 diabetes have not been established. Prescribing Victoza for weight loss is off-label use, which is a decision for a licensed prescriber and is not something this label supports.", "source": { "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/022341s046lbl.pdf", "title": "VICTOZA (liraglutide) injection — Highlights of Prescribing Information", "publisher": "FDA", "date": "2025-10-14", "quote": "VICTOZA is indicated: • as an adjunct to diet and exercise to improve glycemic control in adults and pediatric patients aged 10 years and older with type 2 diabetes mellitus, • to reduce the risk of major adverse cardiovascular events (cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke) in adults with type 2 diabetes mellitus and established cardiovascular disease." }, "verifiedAt": "2026-08-02" }, { "question": "Is liraglutide still on the FDA shortage list in 2026?", "answer": "Yes. FDA's drug shortage database returned ten records for liraglutide injection when queried on 2 August 2026, nine of them with status 'Current'. All nine were initially posted on 18 July 2023, and the most recent FDA reverification among them is 13 July 2026. Six of the nine report availability as 'Available' and three as 'Limited Availability' — a drug stays listed until FDA determines the shortage is resolved, and FDA states that an 'available' status 'reflects the most current information from the manufacturer but is not an FDA determination that the shortage has been resolved.' Two Victoza presentations give the reason as a delay in shipping of the drug, with estimated shortage duration listed as to be determined. A tenth record, a Teva presentation posted 14 May 2026, is a discontinuation notice rather than a shortage. This is a fact about a list and nothing more: it does not by itself make any particular compounded liraglutide product lawful.", "source": { "url": "https://api.fda.gov/drug/shortages.json?search=generic_name:%22liraglutide%22&limit=20", "title": "FDA Drug Shortages Database — liraglutide injection (openFDA drug/shortages endpoint)", "publisher": "FDA", "date": "2026-08-01" }, "verifiedAt": "2026-08-02" }, { "question": "Can compounding pharmacies still make liraglutide in 2026?", "answer": "The two questions people merge here have different answers, so take them apart. On the 503B Bulks List: FDA proposed on 1 May 2026 not to add liraglutide, stating that it 'tentatively finds no basis to conclude that there is a clinical need for an outsourcing facility to compound using the following bulk drug substances: semaglutide, tirzepatide, and liraglutide.' That proposal is tentative and comments closed on 30 June 2026. On the separate shortage route: section 503B of the FD&C Act permits an outsourcing facility to compound from a bulk drug substance where 'the drug compounded from the bulk drug substance appears on the drug shortage list in effect under section 506E of the FD&C Act … at the time of compounding, distribution, and dispensing' — and unlike semaglutide and tirzepatide, liraglutide injection was still on that list when checked on 2 August 2026. So the two statutory doors are in different positions for this drug. What this record does not tell you is whether any specific compounded liraglutide product is lawful: the shortage condition is one of several conditions in section 503B, it is assessed at the time of compounding, distribution and dispensing rather than once, and it does not touch the separate restriction on compounding a product that is essentially a copy of a commercially available drug — which, with two brands and eleven approved generics on the market, is a question a compounder has to answer.", "source": { "url": "https://www.govinfo.gov/content/pkg/FR-2026-05-01/html/2026-08552.htm", "title": "List of Bulk Drug Substances for Which There Is a Clinical Need Under Section 503B of the Federal Food, Drug, and Cosmetic Act (Docket No. FDA-2018-N-3240)", "publisher": "Federal Register / FDA", "date": "2026-05-01", "quote": "the outsourcing facility does not compound a drug using a bulk drug substance unless: (1) the bulk drug substance appears on a list established by the Secretary of Health and Human Services identifying bulk drug substances for which there is a clinical need (the 503B Bulks List) or (2) the drug compounded from the bulk drug substance appears on the drug shortage list in effect under section 506E of the FD&C Act (21 U.S.C. 356e) at the time of compounding, distribution, and dispensing." }, "verifiedAt": "2026-08-02" }, { "question": "Is there a generic version of Victoza or Saxenda?", "answer": "Yes — and unlike semaglutide and tirzepatide, which have no approved generics, liraglutide has many. Drugs@FDA listed eleven approved liraglutide ANDAs on 2 August 2026, from Biocon, Fresenius Kabi, Sandoz, Teva, Lupin, Orbicular, Hikma, Nanjing King Friend and Mylan Institutional; the earliest was approved on 23 December 2024. Seven carry therapeutic equivalence code AP1, meaning they are rated as equivalent to Victoza, and three carry AP2, rated against Saxenda; all eleven show marketing status 'Prescription'. FDA's own 503B notice names one of them, describing an FDA-approved 'liraglutide 18 mg/3 mL, e.g., ANDA 215503' alongside the two brands. One caveat worth keeping: this is a count of approved applications on one day, and approved is not the same as launched — which of them are actually being marketed was not verified here.", "source": { "url": "https://api.fda.gov/drug/drugsfda.json?search=products.active_ingredients.name:%22LIRAGLUTIDE%22&limit=30", "title": "Drugs@FDA — drug products containing liraglutide (openFDA drug/drugsfda endpoint)", "publisher": "FDA", "date": "2026-07-31" }, "verifiedAt": "2026-08-02" }, { "question": "Did FDA find that compounded liraglutide doesn't work?", "answer": "No — FDA's evaluation stopped before that question. FDA's clinical-need analysis under section 503B is sequential, and for liraglutide it ended at the threshold: 'Because there is no basis to conclude that there is an attribute of the FDA-approved drug products containing liraglutide which makes them medically unsuitable to treat certain patients, FDA need not decide whether the proposed drug products containing liraglutide must be compounded from a bulk drug substance rather than using an FDA-approved drug product.' What FDA actually evaluated was narrow — whether the nomination identified an attribute of the approved liraglutide products making them medically unsuitable for identified patients. It found it did not: the only compounded strength the nominator identified was the same as the approved products', the inactive ingredients patients were said to be intolerant of were never named, and the propylene-glycol argument rested on an article that, as FDA recorded, 'did not evaluate liraglutide'. FDA also noted in the same notice that arguments about safety and quality concerns with the nominated bulk drug substances 'would be addressed in Part 2 of the clinical need analysis, which we do not reach here.' So the proposal is not a verdict that compounded liraglutide is ineffective, and the absence of such a verdict is not evidence that it works.", "source": { "url": "https://www.govinfo.gov/content/pkg/FR-2026-05-01/html/2026-08552.htm", "title": "List of Bulk Drug Substances for Which There Is a Clinical Need Under Section 503B of the Federal Food, Drug, and Cosmetic Act (Docket No. FDA-2018-N-3240)", "publisher": "Federal Register / FDA", "date": "2026-05-01", "quote": "Because there is no basis to conclude that there is an attribute of the FDA-approved drug products containing liraglutide which makes them medically unsuitable to treat certain patients, FDA need not decide whether the proposed drug products containing liraglutide must be compounded from a bulk drug substance rather than using an FDA-approved drug product." }, "verifiedAt": "2026-08-02" } ] }, { "slug": "ll-37", "name": "LL-37", "aliases": [ "Cathelicidin LL-37", "cathelicidin antimicrobial peptide", "hCAP-18", "CAP-18", "LL-37 (CAP-18)", "LL-37 acetate", "ropocamptide" ], "url": "https://peptides101.com/compounds/ll-37", "moleculeNote": "LL-37 is the mature 37-residue C-terminal peptide released by proteolytic cleavage from the human cathelicidin precursor protein hCAP-18. Two disambiguations carry most of this record. FIRST, LL-37 IS ENDOGENOUS. It is already present in human neutrophils, epithelia, saliva, gingival crevicular fluid and wound fluid, with nobody administering anything. That single fact reverses the meaning of most of the literature filed under its name: a study 'of LL-37' in humans is usually a study that MEASURED a peptide the subject already had, frequently as a readout of vitamin D status or smoking. It is not a study of a drug. SECOND, NAMES. The synthetic peptide taken into clinical trials carries the non-proprietary name ropocamptide; FDA files the compounding entry as 'Cathelicidin LL-37'; and FDA's National Drug Code Directory carries separate bulk-ingredient entries reading 'LL-37', 'LL-37 (CAP-18)' and 'LL-37 Acetate' from four different labelers, one of which records the active ingredient as ROPOCAMPTIDE. A label reading 'LL-37' does not by itself identify a salt form.", "quickAnswer": "LL-37 is not an FDA-approved drug for any indication; its only presence in an FDA drug database is as bulk ingredient listings in the National Drug Code Directory, and FDA states that assignment of an NDC number 'does not in any way denote FDA approval of the product'. LL-37 was nominated for use in pharmacy compounding under section 503A and FDA lists Cathelicidin LL-37 under 'Bulk drug substances nominated but withdrawn' — substances previously in category 2, the category for significant safety risks, whose nominations the nominators withdrew — and it appears in none of Categories 1, 2 or 3 of the 503A list updated 14 May 2026. FDA states it lacks sufficient safety-related information regarding cathelicidin LL-37 to know whether the drug would cause harm when administered to humans, and that nonclinical research findings suggest detrimental effects on male reproduction and that the drug can be protumorigenic in some tissues. In the largest trial to administer LL-37 to people — a phase IIb double-blind randomised placebo-controlled study of a topical formulation in 148 patients with hard-to-heal venous leg ulcers — the investigators reported that 'Efficacy analysis performed on the full study population did not identify any significant improvement in healing in patients treated with LL-37 as compared with the placebo.'", "fdaStatus": { "value": "not-approved", "note": "Not approved, and — this is the part that required a decision rather than a lookup — not investigational either. ABSENCE FROM Drugs@FDA, CHECKED PROPERLY. A NOT_FOUND from one wrong field is an artifact of the query, not a fact about the database, so the openFDA drug/drugsfda endpoint was queried on 2026-08-02 across every field that could carry it: openfda.generic_name, openfda.substance_name, products.active_ingredients.name and products.brand_name, each for 'LL-37', 'cathelicidin' and 'ropocamptide', plus unfielded full-text searches for all three. Every one returned no match. There is no NDA, no ANDA and no BLA. WHAT DOES EXIST is four entries in FDA's NDC Directory, every one with marketing_category 'BULK INGREDIENT' and a null application number — recorded separately under fdaFindings, because a bulk-ingredient listing is the single most misread artifact in this market. WHY NOT 'investigational'. LL-37 did have a real programme with a real sponsor: Pergamum AB and then Promore Pharma AB developed it under the non-proprietary name ropocamptide, through a first-in-man trial and a 148-patient phase IIb. That programme is over. Promore Pharma entered voluntary liquidation by decision of an extraordinary general meeting on 5 October 2023, having stated that the climate for the share issues needed to finance continued development of ropocamptide was very challenging, and the listed entity was then used for a reverse acquisition of an unrelated medical-device business. The vocabulary here is explicit that a terminated or abandoned programme is not investigational, and no successor sponsor, no new registered trial and no active recruitment administering LL-37 was identified as of 2026-08-02. 'In clinical trials' is sold on the strength of trials that stopped years ago; this is one of those.", "source": { "url": "https://www.fda.gov/drugs/drug-approvals-and-databases/national-drug-code-directory", "title": "National Drug Code Directory", "publisher": "FDA", "date": "2026-03-04", "quote": "Inclusion in the NDC Directory does not indicate that FDA has verified the information provided or that the products are FDA-approved. … Assignment of an NDC number does not in any way denote FDA approval of the product. Any representation that creates an impression of FDA approval because a product has an NDC number is misleading and violates federal law." }, "verifiedAt": "2026-08-02" }, "compoundingStatus": { "value": "withdrawn-from-nomination", "note": "Read the direction of travel, because the market reads it backwards. Cathelicidin LL-37 was PREVIOUSLY IN CATEGORY 2 — the category FDA reserves for substances that may present significant safety risks — and it left because the nominators withdrew, not because FDA resolved anything in its favour. It did not enter Category 1. It is not on the 503A bulks list. It appears in none of Categories 1, 2 or 3 of the list updated 2026-05-14, verified on 2026-08-02 by fetching that PDF with a browser user-agent and extracting its text: zero hits for 'LL-37', 'cathelicidin' and 'ropocamptide' across all seven pages. Status moved sideways, and FDA left its safety concerns published on a page it never took down. NOT ONE OF THE SEVEN. Cathelicidin LL-37 was not among the substances before the Pharmacy Compounding Advisory Committee on 23-24 July 2026, so none of what that committee recommended reaches it — see fdaFindings.", "source": { "url": "https://www.fda.gov/drugs/human-drug-compounding/certain-bulk-drug-substances-use-compounding-may-present-significant-safety-risks", "title": "Certain Bulk Drug Substances for Use in Compounding that May Present Significant Safety Risks", "publisher": "FDA", "date": "2026-04-22", "quote": "Bulk drug substances nominated but withdrawn — This list of bulk drug substances previously in category 2 of the interim policies were withdrawn by the nominators. … Cathelicidin LL-37" }, "verifiedAt": "2026-08-02" }, "evidence": { "tier": "promising-but-unproven", "humanAdministrationChecked": true, "note": "ADMINISTRATION CHECK RUN, AND IT MATTERED. LL-37 is endogenous, which is the exact condition that reduces MOTS-c and TB-500 from an apparent handful of human RCTs to an actual zero, so every candidate study was opened rather than counted. The count, performed 2026-08-02: an intervention query for 'LL-37' on ClinicalTrials.gov returns 20 studies. EIGHTEEN of them do not administer it — they measure endogenous LL-37 in saliva, serum, gingival crevicular fluid or peri-implant sulcus fluid, most often as a readout of vitamin D supplementation, smoking exposure or periodontal disease. Two administer it: NCT02225366 (M.D. Anderson with NCI, intratumoral injection in melanoma, phase 1/2, 4 participants ACTUAL, completed 2020-11-24, results posted) and NCT04098562 (topical cream in diabetic foot ulcers, Universitas Indonesia, last known status UNKNOWN since 2019, enrolment only ESTIMATED — treat it as unreported). THE TWO THAT COUNT ARE NOT ON ClinicalTrials.gov AT ALL, which is why a registry-only search understates this compound. Both were European and both administered synthetic LL-37 topically to human wounds: Grönberg et al. 2014, a first-in-man randomised placebo-controlled trial in 34 participants with venous leg ulcers, sponsor Pergamum AB; and the trial cited above, HEAL LL-37 (EudraCT 2018-000536-10), a phase IIb double-blind randomised placebo-controlled study in 148 patients with hard-to-heal venous leg ulcers, sponsor Promore Pharma AB. Both abstracts were retrieved through the NCBI E-utilities efetch endpoint and the phase IIb was opened in full on PMC. LL-37 was given to people. WHY THE TIER IS NOT HIGHER. The phase IIb did not succeed. The investigators reported that efficacy analysis in the full study population did not identify any significant improvement in healing versus placebo, and the positive result they describe is confined to a POST HOC analysis in the subgroup with large target wounds — the authors' own word is 'post hoc', and their conclusion asks for 'a further study adequately powered' to assess that group. That study was never run: the sponsor liquidated in October 2023. This tier is assigned because the vocabulary reserves 'promising-but-unproven' for programmes with a human signal that were tested and not established, explicitly including ones that failed. This is one that failed. THE GAP THAT MATTERS MOST IS ROUTE AND INDICATION. Every human administration of LL-37 identified here was either topical application to a chronic leg ulcer under compression, or injection directly into a cutaneous melanoma lesion. Nothing in this evidence base describes systemic subcutaneous or nasal use, and nothing in it addresses immune support, gut health, chronic infection or biofilm — the claims the consumer market is built on. A trial of a wound gel is not evidence for an injected vial.", "source": { "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC9298190/", "title": "Evaluation of LL-37 in healing of hard-to-heal venous leg ulcers: A multicentric prospective randomized placebo-controlled clinical trial (Mahlapuu et al., Wound Repair and Regeneration 2021;29(6):938-950)", "publisher": "PubMed Central", "date": "2021-10-23", "quote": "Efficacy analysis performed on the full study population did not identify any significant improvement in healing in patients treated with LL-37 as compared with the placebo." }, "verifiedAt": "2026-08-02" }, "fdaApproval": null, "fdaFindings": [ { "finding": "FDA lists Cathelicidin LL-37 in the table headed 'Bulk drug substances nominated but withdrawn' on its page identifying bulk drug substances that may present significant safety risks — a list FDA describes as substances previously in category 2 of the interim policies whose nominations were withdrawn by the nominators.", "note": "Verified by fetching the page with a browser user-agent and parsing its two tables rather than reading the flattened text, because the flattened text does not tell you which table a row is in and that is the entire question. Table 1 is Category 2 and holds fifteen rows; 'Cathelicidin LL-37' is not in it. Table 2 is the withdrawn table and holds seventeen entries; 'Cathelicidin LL-37' is one of them, filed alphabetically between BPC-157 and CJC-1295. The practical consequence is the one people get wrong: withdrawal moved LL-37 off Category 2 and nowhere else. FDA's stated concerns about it stayed published.", "source": { "url": "https://www.fda.gov/drugs/human-drug-compounding/certain-bulk-drug-substances-use-compounding-may-present-significant-safety-risks", "title": "Certain Bulk Drug Substances for Use in Compounding that May Present Significant Safety Risks", "publisher": "FDA", "date": "2026-04-22", "quote": "This list of bulk drug substances previously in category 2 of the interim policies were withdrawn by the nominators." }, "verifiedAt": "2026-08-02" }, { "finding": "Cathelicidin LL-37 appears in none of Categories 1, 2 or 3 of FDA's list of bulk drug substances nominated for use in compounding under section 503A, updated 14 May 2026.", "note": "Recorded to close a misreading, not to establish the status — absence from this document proves absence and nothing more, which is why the withdrawal above is sourced to the safety-risks page instead. Verified on 2026-08-02 by fetching the PDF with a browser user-agent and extracting all seven pages locally: zero hits for 'LL-37', 'LL37', 'cathelicidin' and 'ropocamptide'. This is precisely the trap that produced a false 'never nominated' reading elsewhere in this library. LL-37 is invisible in the document most people check, and present in the one they do not.", "source": { "url": "https://www.fda.gov/media/94155/download", "title": "Bulk Drug Substances Nominated for Use in Compounding Under Section 503A of the Federal Food, Drug, and Cosmetic Act", "publisher": "FDA", "date": "2026-05-14" }, "verifiedAt": "2026-08-02" }, { "finding": "Cathelicidin LL-37 was not among the bulk drug substances before FDA's Pharmacy Compounding Advisory Committee at its meeting of 23-24 July 2026.", "note": "Verified by fetching the agenda PDF and extracting its text on 2026-08-02: zero hits for 'LL-37' and zero for 'cathelicidin'. The substances the agenda does name are BPC-157, KPV, TB-500, MOTS-c, semax, epitalon and emideltide (DSIP). This matters because of what is about to be written about that meeting. Coverage of the July 2026 committee recommendations is being read across the peptide category as a general softening, and LL-37 was not in the room. It received no recommendation, favourable or otherwise, and nothing about its position changed in July 2026.", "source": { "url": "https://www.fda.gov/media/193771/download", "title": "Pharmacy Compounding Advisory Committee Meeting, July 23-24, 2026 — Agenda", "publisher": "FDA", "date": "2026-07-23" }, "verifiedAt": "2026-08-02" }, { "finding": "LL-37's only presence in an FDA drug database is as bulk ingredient listings in the National Drug Code Directory. As of the openFDA data current to 31 July 2026 there are four, from Qingdao Biopeptek Co., Ltd., Nanjing Chengong Pharmaceutical Co., Ltd., DARMERICA, LLC and Pure Peptide Pharmaceuticals Inc., every one carrying the marketing category 'BULK INGREDIENT', the dosage form POWDER, and no application number.", "note": "The most misread artifact in this market, recorded so it can be checked in one request. An NDC is a listing identifier, not an approval, and FDA says so in terms: 'Assignment of an NDC number does not in any way denote FDA approval of the product. Any representation that creates an impression of FDA approval because a product has an NDC number is misleading and violates federal law.' FDA's page also describes the directory as containing 'finished and unfinished drugs' and as covering 'approved and unapproved drugs'. A supplier holding an NDC for LL-37 powder has registered and listed; it has not been approved, reviewed or endorsed. Two details worth reading. The Nanjing listing records its active ingredient as ROPOCAMPTIDE under the generic name 'LL-37 (CAP-18)', which is the clearest single confirmation in an FDA database that the drug-candidate name and the research-peptide name denote the same molecule. And two of the four listings record marketing start dates of 2025-12-08 and 2026-05-01 — this is current supply, not a legacy entry.", "source": { "url": "https://api.fda.gov/drug/ndc.json?search=generic_name:%22LL-37%22&limit=10", "title": "openFDA National Drug Code Directory API — query for generic_name \"LL-37\"", "publisher": "FDA", "date": "2026-07-31" }, "verifiedAt": "2026-08-02" } ], "safetySignals": [ { "signal": "FDA states that compounded drugs containing cathelicidin LL-37 may pose a risk for immunogenicity for certain routes of administration and may have complexities with regard to peptide-related impurities and active pharmaceutical ingredient characterization, and that FDA lacks sufficient safety-related information regarding cathelicidin LL-37 to know whether the drug would cause harm when administered to humans.", "note": "Note the shape of the finding: it is a statement about missing information, not a report of harm, and those are different things that get collapsed in both directions. It cuts against 'no adverse events have been reported, so it is safe' — FDA is saying the information needed to answer the question does not exist. It equally does not establish that LL-37 has hurt anyone. Read it against this record's evidence section rather than alone. Human tolerability data does exist for one route: the investigators in both venous-leg-ulcer trials reported that topical LL-37 was well tolerated, and the 2014 trial reported no safety concerns regarding local or systemic adverse events. That is a finding about a wound gel applied to skin. FDA's concern is expressly about routes of administration and about what is in a bulk substance, and neither of those is answered by a topical trial.", "source": { "url": "https://www.fda.gov/drugs/human-drug-compounding/certain-bulk-drug-substances-use-compounding-may-present-significant-safety-risks", "title": "Certain Bulk Drug Substances for Use in Compounding that May Present Significant Safety Risks", "publisher": "FDA", "date": "2026-04-22", "quote": "Compounded drugs containing cathelicidin LL-37 may pose risk for immunogenicity for certain routes of administration and may have complexities with regard to peptide-related impurities and API characterization. FDA lacks sufficient safety-related information regarding cathelicidin LL-37 to know whether the drug would cause harm when administered to humans." }, "verifiedAt": "2026-08-02" }, { "signal": "FDA states that nonclinical research findings suggest detrimental effects on male reproduction and that cathelicidin LL-37 can be protumorigenic in some tissues.", "note": "The most specific negative finding FDA publishes about this substance, and it is worth isolating from the boilerplate it sits next to. The immunogenicity and characterization language above is close to identical across a dozen entries on FDA's page; this sentence is written for LL-37 alone. Only three of the seventeen withdrawn entries carry a substance-specific nonclinical finding at all. Two limits, stated because the finding is strong enough not to need overstating. It is NONCLINICAL — FDA's word — so it does not describe an observed effect in a person. And FDA gives no citation to the underlying research on this page, so what is verifiable here is that FDA said it, not the primary data behind it. It is also the reason this record's marketing gap is not merely an efficacy gap. LL-37 is sold into a market that reads an endogenous human peptide as inherently safe because the body already makes it. FDA's stated concerns run the other way, and 'protumorigenic in some tissues' is not a claim any seller of this compound discloses.", "source": { "url": "https://www.fda.gov/drugs/human-drug-compounding/certain-bulk-drug-substances-use-compounding-may-present-significant-safety-risks", "title": "Certain Bulk Drug Substances for Use in Compounding that May Present Significant Safety Risks", "publisher": "FDA", "date": "2026-04-22", "quote": "Nonclinical research findings suggest detrimental effects on male reproduction and that this drug can be protumorigenic in some tissues." }, "verifiedAt": "2026-08-02" } ], "faqs": [ { "question": "Is LL-37 FDA-approved?", "answer": "No. LL-37 is not an approved drug product in the United States under any name — not LL-37, not cathelicidin LL-37, and not ropocamptide, the non-proprietary name under which it was developed as a drug candidate. Searching FDA's Drugs@FDA database through the openFDA drug/drugsfda endpoint on 2 August 2026 across generic name, substance name, active-ingredient name and brand name, plus unfielded full-text search, returned no match for any of those three names: there is no NDA, ANDA or BLA. What does exist, and what gets mistaken for approval, is a listing. LL-37 appears in FDA's National Drug Code Directory as four bulk-ingredient entries from peptide API suppliers, each carrying an NDC number. FDA is unusually blunt about what that means: 'Inclusion in the NDC Directory does not indicate that FDA has verified the information provided or that the products are FDA-approved… Assignment of an NDC number does not in any way denote FDA approval of the product. Any representation that creates an impression of FDA approval because a product has an NDC number is misleading and violates federal law.' FDA also describes the directory as covering 'approved and unapproved drugs'. A supplier with an NDC has registered and listed a product; nobody has approved it.", "source": { "url": "https://www.fda.gov/drugs/drug-approvals-and-databases/national-drug-code-directory", "title": "National Drug Code Directory", "publisher": "FDA", "date": "2026-03-04", "quote": "Inclusion in the NDC Directory does not indicate that FDA has verified the information provided or that the products are FDA-approved. The content of each NDC Directory entry is the responsibility of the labeler submitting the SPL file. Assignment of an NDC number does not in any way denote FDA approval of the product. Any representation that creates an impression of FDA approval because a product has an NDC number is misleading and violates federal law." }, "verifiedAt": "2026-08-02" }, { "question": "Can a compounding pharmacy legally make LL-37?", "answer": "Not under section 503A. Cathelicidin LL-37 is not on FDA's 503A bulk drug substances list — it appears in none of Categories 1, 2 or 3 of the list updated 14 May 2026, verified by extracting that document directly — and it is not an active ingredient in any FDA-approved drug product. The history is the part that gets reported backwards. Cathelicidin LL-37 was nominated, and FDA placed it in category 2, the category for bulk drug substances that may present significant safety risks. It then left category 2, and it left for one reason: FDA lists it in a table headed 'Bulk drug substances nominated but withdrawn', which FDA describes as substances 'previously in category 2 of the interim policies' that 'were withdrawn by the nominators'. A nominator giving up is not FDA changing its mind. LL-37 did not move into Category 1, it did not reach the bulks list, and FDA left its safety concerns about it published on the same page that records the withdrawal.", "source": { "url": "https://www.fda.gov/drugs/human-drug-compounding/certain-bulk-drug-substances-use-compounding-may-present-significant-safety-risks", "title": "Certain Bulk Drug Substances for Use in Compounding that May Present Significant Safety Risks", "publisher": "FDA", "date": "2026-04-22", "quote": "Bulk drug substances nominated but withdrawn — This list of bulk drug substances previously in category 2 of the interim policies were withdrawn by the nominators. … Cathelicidin LL-37" }, "verifiedAt": "2026-08-02" }, { "question": "Is there human evidence that LL-37 works?", "answer": "There is human evidence, and the largest trial of it did not succeed. HEAL LL-37 (EudraCT 2018-000536-10) was a phase IIb double-blind randomised placebo-controlled study run by Promore Pharma AB in 148 patients with hard-to-heal venous leg ulcers, testing a topical LL-37 formulation alongside compression therapy. The investigators reported: 'Efficacy analysis performed on the full study population did not identify any significant improvement in healing in patients treated with LL-37 as compared with the placebo.' A positive result was reported, but the authors describe it as a POST HOC analysis restricted to the subgroup with large target wounds, and their own conclusion calls for 'a further study adequately powered to statistically assess the treatment outcome in this patient group'. That confirmatory study was never run. Read the scope before carrying any of this across. This trial studied a topical formulation applied to open leg ulcers under compression bandaging. It is not evidence about injected or nasal LL-37, and it says nothing about immune support, gut health, chronic infection or biofilm, which are the uses LL-37 is marketed for.", "source": { "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC9298190/", "title": "Evaluation of LL-37 in healing of hard-to-heal venous leg ulcers: A multicentric prospective randomized placebo-controlled clinical trial (Mahlapuu et al., Wound Repair and Regeneration 2021;29(6):938-950)", "publisher": "PubMed Central", "date": "2021-10-23", "quote": "Efficacy analysis performed on the full study population did not identify any significant improvement in healing in patients treated with LL-37 as compared with the placebo. In contrast, a post hoc analysis revealed statistically significant improvement with LL-37 treatment in several interrelated healing parameters in the subgroup of patients with large target wounds …" }, "verifiedAt": "2026-08-02" }, { "question": "Has LL-37 ever actually been given to people, or do the studies just measure it in the body?", "answer": "Both — and separating the two is the single most important thing to get right about this compound. LL-37 is endogenous: it is already present in human neutrophils, epithelia, saliva and wound fluid, so a study can carry 'LL-37' in its title while administering nothing at all. Of the 20 studies ClinicalTrials.gov returns for an LL-37 intervention query, checked one by one on 2 August 2026, eighteen measure endogenous LL-37 as a biomarker — in saliva, serum, gingival crevicular fluid or peri-implant sulcus fluid — most often as a readout of vitamin D supplementation, smoking exposure or gum disease. Those are not trials of a drug. Genuine administration studies do exist, and the earliest is a first-in-man trial published in 2014: Grönberg and colleagues randomised 34 participants with hard-to-heal venous leg ulcers to topical LL-37 or placebo, sponsored by Pergamum AB, and reported 'There were no safety concerns regarding local or systemic adverse events.' A larger phase IIb followed in 148 patients, and separately M.D. Anderson Cancer Center with the National Cancer Institute injected LL-37 directly into melanoma lesions in a phase 1/2 study that completed with 4 participants enrolled (NCT02225366). So the honest count is small but not zero. What none of these studies did is administer LL-37 by the routes it is sold for, or for the reasons it is sold.", "source": { "url": "https://pubmed.ncbi.nlm.nih.gov/25041740/", "title": "Treatment with LL-37 is safe and effective in enhancing healing of hard-to-heal venous leg ulcers: a randomized, placebo-controlled clinical trial (Grönberg et al., Wound Repair and Regeneration 2014;22(5):613-21)", "publisher": "PubMed", "date": "2014-09-01", "quote": "This first-in-man trial included 34 participants with VLUs … There were no safety concerns regarding local or systemic adverse events. In conclusion, topical treatment with LL-37 for chronic leg ulcers was safe and well tolerated with the marked effect on healing predictors … warranting further investigations." }, "verifiedAt": "2026-08-02" }, { "question": "Did FDA's July 2026 advisory committee vote cover LL-37?", "answer": "No. Cathelicidin LL-37 was not among the substances before the Pharmacy Compounding Advisory Committee at its meeting of 23-24 July 2026. The seven bulk drug substances on that agenda were BPC-157, KPV, TB-500, MOTS-c, semax, epitalon and emideltide (DSIP); extracting the agenda document returns no mention of LL-37 or cathelicidin anywhere in it. LL-37 therefore received no recommendation at that meeting, favourable or unfavourable, and nothing about its position changed in July 2026. This is worth stating explicitly because coverage of that meeting is being read across the whole peptide category. Two separate things would have to be true for it to reach LL-37, and neither is: LL-37 was not on the agenda, and in any case an advisory committee recommendation is not a rule — FDA's own description is that advisory committees make non-binding recommendations which the agency generally follows but is not legally bound to follow.", "source": { "url": "https://www.fda.gov/media/193771/download", "title": "Pharmacy Compounding Advisory Committee Meeting, July 23-24, 2026 — Agenda", "publisher": "FDA", "date": "2026-07-23" }, "verifiedAt": "2026-08-02" }, { "question": "Is LL-37 safe?", "answer": "Unknown, and FDA has said so in terms while also publishing two specific concerns. On the general question FDA states that it 'lacks sufficient safety-related information regarding cathelicidin LL-37 to know whether the drug would cause harm when administered to humans', and that compounded drugs containing it 'may pose risk for immunogenicity for certain routes of administration and may have complexities with regard to peptide-related impurities and API characterization'. More specifically, FDA states that 'Nonclinical research findings suggest detrimental effects on male reproduction and that this drug can be protumorigenic in some tissues.' That sentence is written for LL-37 alone rather than shared with the other entries on FDA's page, and it is nonclinical — it describes laboratory and animal findings, not an observed effect in a person. There is genuine human tolerability data, and it is narrow: investigators in two European trials of a TOPICAL formulation applied to venous leg ulcers reported it was well tolerated, with the 2014 trial reporting no safety concerns regarding local or systemic adverse events. That is a finding about a wound preparation on skin, and it does not transfer to an injected or nasal product. The intuition to distrust here is the one this compound invites: LL-37 is a peptide the human body already makes, which is widely treated as meaning it must be harmless. Endogenous is not the same as safe at an administered exposure by an unstudied route, and FDA's published concerns run in the opposite direction.", "source": { "url": "https://www.fda.gov/drugs/human-drug-compounding/certain-bulk-drug-substances-use-compounding-may-present-significant-safety-risks", "title": "Certain Bulk Drug Substances for Use in Compounding that May Present Significant Safety Risks", "publisher": "FDA", "date": "2026-04-22", "quote": "Compounded drugs containing cathelicidin LL-37 may pose risk for immunogenicity for certain routes of administration and may have complexities with regard to peptide-related impurities and API characterization. FDA lacks sufficient safety-related information regarding cathelicidin LL-37 to know whether the drug would cause harm when administered to humans. Nonclinical research findings suggest detrimental effects on male reproduction and that this drug can be protumorigenic in some tissues." }, "verifiedAt": "2026-08-02" } ] }, { "slug": "mazdutide", "name": "Mazdutide", "aliases": [ "IBI362", "LY3305677", "Xinermei" ], "url": "https://peptides101.com/compounds/mazdutide", "moleculeNote": "Described in the NEJM report of its pivotal Phase 3 trial as 'a glucagon-like peptide-1 and glucagon receptor dual agonist'. The receptor combination is the disambiguation that matters, because the three compounds it is shelved beside are each a different molecule acting on a different set of receptors: semaglutide is a GLP-1 receptor agonist, tirzepatide agonises GIP and GLP-1, and retatrutide agonises GIP, GLP-1 and glucagon. Mazdutide is the GLP-1-plus-glucagon combination, and none of the four is interchangeable with another. There is no fragment-versus-full-length ambiguity in the literature: 'mazdutide', 'IBI362' and 'LY3305677' denote one molecule, originated at Eli Lilly and developed in China by Innovent Biologics. The ambiguity is elsewhere — nothing verifies that a vial sold as 'mazdutide' by a research-chemical vendor contains that molecule at any purity or content, and mazdutide is not an active ingredient in any FDA-approved drug product, so no vial of it in the United States comes from an approved supply.", "quickAnswer": "Mazdutide (IBI362, LY3305677) is not approved by FDA for any indication — FDA stated in a warning letter of 31 March 2026 that products sold as 'Mazdutide' by a US website are unapproved new drugs and that 'No approved applications pursuant to section 505 of the FD&C Act … are in effect for these products', and FDA had made the same finding against a different seller in December 2024. Mazdutide is, however, an approved prescription medicine in China, where it was approved in June 2025 for long-term body weight management in adults and in September 2025 for glycaemic control in adults with type 2 diabetes; a Chinese approval has no legal effect in the United States. Its human evidence is genuine and published: in the Phase 3 GLORY-1 trial reported in the New England Journal of Medicine in June 2025, investigators randomly assigned 610 Chinese adults with obesity or overweight to mazdutide or placebo and reported mean body-weight changes at week 32 of -10.09% and -12.55% in the two mazdutide groups against +0.45% with placebo, and in the Phase 3 GLORY-2 trial reported in JAMA in June 2026, 461 Chinese adults received treatment and investigators reported a mean body-weight change at week 60 of -16.65% with mazdutide against -1.50% with placebo, with vomiting in 53.1%, nausea in 46.9% and diarrhea in 39.4% of the mazdutide group. Those trials describe the sponsors' investigational material under trial conditions in Chinese populations, and say nothing about the contents of a vial sold online.", "fdaStatus": { "value": "investigational", "note": "Two claims, verified separately. NOT APPROVED BY FDA: the quoted finding is FDA's, made on 2026-03-31 about products offered for sale as 'Mazdutide' by a US website, and it is corroborated by seven Drugs@FDA queries returning NOT_FOUND on 2026-08-02. IN ACTIVE DEVELOPMENT: verified against the ClinicalTrials.gov API on 2026-08-02, which returned 36 registrations naming mazdutide, IBI362 or LY3305677. Two sponsors carry the programme. Eli Lilly and Company holds the US-registered trials — NCT06124807 (Phase 2, 179 participants, 29 US sites, COMPLETED 2025-07-09, results posted), NCT06817356 (Phase 2, alcohol use disorder, 308 participants, 25 US sites, COMPLETED 2026-05-19) and the CWMM master protocol NCT06143956, which is RECRUITING at 54 sites in the US and Argentina with LY3305677 listed among its interventions and estimated completion in 2028. Innovent Biologics (Suzhou) Co. Ltd. holds the Phase 3 programme, including registrations that began recruiting as recently as 2026-04-23 (NCT07469800). HONEST LIMITS, and they matter for how this label should be read. Every Phase 3 registration located for this record is conducted in China; the registered US trials are Phase 2. This record makes NO claim about whether an IND or a marketing application exists for mazdutide in the United States — INDs are not public, and Drugs@FDA lists applications, not investigations, so silence there is not evidence either way. What is recorded is what the registries and Drugs@FDA actually show. Being in trials is not evidence that a compound works, and it is not permission to buy one.", "source": { "url": "https://www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/warning-letters/prime-sciences-721805-03312026", "title": "Warning Letter — Prime Sciences (MARCS-CMS 721805)", "publisher": "FDA", "date": "2026-03-31", "quote": "No approved applications pursuant to section 505 of the FD&C Act, 21 U.S.C. 355, are in effect for these products. Accordingly, these products are unapproved new drugs." }, "verifiedAt": "2026-08-02" }, "compoundingStatus": null, "evidence": { "tier": "proven-in-humans", "humanAdministrationChecked": true, "note": "ADMINISTRATION CHECK RUN, NOT ASSUMED. Mazdutide is a synthetic investigational peptide and not an endogenous human peptide, so the biomarker trap that empties MOTS-c's and TB-500's apparent trial counts cannot arise here — but the check was run per-study anyway. In GLORY-1 (NCT05607680, NEJM 2025) investigators randomly assigned 610 Chinese adults with obesity or overweight to receive mazdutide or placebo and reported mean percentage changes in body weight from baseline at week 32 of -10.09% and -12.55% in the two mazdutide groups versus +0.45% with placebo, with 73.9% and 82.0% of mazdutide participants versus 10.5% of placebo participants achieving a reduction of at least 5% (P<0.001 for all comparisons with placebo). In GLORY-2 (NCT06164873, JAMA 2026), a double-blind placebo-controlled Phase 3 trial at 27 hospitals running from December 2023 to November 2025, 461 Chinese adults with obesity received treatment and investigators reported a mean change in body weight at week 60 of -16.65% with mazdutide versus -1.50% with placebo. The ClinicalTrials.gov intervention records for both read as a DRUG administered subcutaneously, and both trials were funded by Innovent Biologics. Mazdutide has also been administered to humans in the United States: NCT06124807, an Eli Lilly Phase 2 obesity trial at 29 US sites, completed 2025-07-09 with results posted. WHAT THIS TIER DOES AND DOES NOT MEAN. It means efficacy on the endpoint those trials measured — body weight — is established by adequate, well-controlled human trials. It does NOT mean FDA-approved; FDA has made no safety-and-effectiveness finding on mazdutide, and has found products sold as mazdutide in the US to be unapproved new drugs. It does not mean the evidence generalises freely: every Phase 3 trial cited here enrolled Chinese adults in China, the trials were 48 to 60 weeks long, and no cardiovascular or kidney outcomes trial of mazdutide has reported. And it does not transfer to grey-market product — these findings describe Innovent's and Lilly's investigational material under trial conditions, not the contents of a vial bought online. Per-arm strengths are left to the cited papers deliberately.", "source": { "url": "https://pubmed.ncbi.nlm.nih.gov/40421736/", "title": "Once-Weekly Mazdutide in Chinese Adults with Obesity or Overweight", "publisher": "The New England Journal of Medicine", "date": "2025-06-12", "quote": "In a phase 3, double-blind, placebo-controlled trial in China, we randomly assigned, in a 1:1:1 ratio, adults 18 to 75 years of age who had a body-mass index … of at least 28 or had a BMI of 24 to less than 28 plus at least one weight-related coexisting condition to receive […] mazdutide […] or placebo for 48 weeks." }, "verifiedAt": "2026-08-02" }, "fdaApproval": null, "fdaFindings": [ { "finding": "FDA found that products offered for sale as 'Mazdutide' by a US website are unapproved new drugs under section 505(a) of the Federal Food, Drug, and Cosmetic Act, and that introducing or delivering them for introduction into interstate commerce violates sections 301(d) and 505(a).", "note": "FDA naming mazdutide, in writing, as recently as March 2026. Read the scope precisely in both directions. This is a finding about a seller's products, not a pharmacological finding about the molecule, and it binds that firm — it is cited here as evidence of FDA's legal position on mazdutide sold this way, not as a claim about any other vendor. But it is also not a technicality: FDA states flatly that no approved section 505 applications are in effect for these products, which is the same thing seven Drugs@FDA queries showed independently. Note also the reconstitution-kit finding, which reaches further than most readers expect — FDA held that selling bacteriostatic water together with a syringe alongside peptide products 'demonstrates that you intend for the “BAC water” to be used in combination for injection. Therefore, your “BAC water” is a drug.'", "source": { "url": "https://www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/warning-letters/prime-sciences-721805-03312026", "title": "Warning Letter — Prime Sciences (MARCS-CMS 721805)", "publisher": "FDA", "date": "2026-03-31", "quote": "The FDA has observed that your website offers “Cagrilintide,” “GLP1-R,” “GLP1-S,” “GLP1-T,” “Mazdutide,” and “BAC water” … for sale in the United States. Based on our review, these products are unapproved new drugs under section 505(a) of the Federal Food, Drug, and Cosmetic Act (FD&C Act), 21 U.S.C. 355(a)." }, "verifiedAt": "2026-08-02" }, { "finding": "FDA held that labeling mazdutide and other peptide products for 'laboratory research purposes only' and 'not for human consumption, medical use or veterinary use' did not defeat evidence of intended use obtained from the seller's own website.", "note": "The research-label theory, applied to mazdutide, and failing on the same reasoning FDA has used against it repeatedly elsewhere in this library. What makes this letter instructive is WHICH evidence FDA cited from the mazdutide product page: the seller's own invocation of the Chinese Phase 3 programme. FDA reproduced the claim 'Mazdutide peptide therapy benefits include: … Significant weight loss: In a phase 3 trial (GLORY-1), once-weekly mazdutide led to an average body weight reduction of up to 14.8%' as evidence that the product was intended as a drug for human use. That is the laundering mechanism this record exists to interrupt: a real, published, peer-reviewed trial of a sponsor's investigational material, quoted on a webpage to sell an unverified vial, and treated by FDA as the exhibit rather than the defence.", "source": { "url": "https://www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/warning-letters/prime-sciences-721805-03312026", "title": "Warning Letter — Prime Sciences (MARCS-CMS 721805)", "publisher": "FDA", "date": "2026-03-31", "quote": "Despite statements on your product labeling marketing your products for “laboratory research purposes only” and “not for human consumption, medical use or veterinary use,” evidence obtained from your website establishes that your products are intended to be drugs for human use." }, "verifiedAt": "2026-08-02" }, { "finding": "In an earlier warning letter, FDA found products offered as 'Mazdutide' alongside semaglutide, retatrutide, cagrilintide and tirzepatide to be unapproved new drugs introduced into interstate commerce in violation of sections 505(a) and 301(d), notwithstanding labeling marketing them as 'RESEARCH USE ONLY'.", "note": "Recorded because two letters fifteen months apart establish a standing FDA position rather than a one-off 2026 action. The specific claim FDA cited from this seller's mazdutide page is worth reading against the site's own house style: 'Mazdutide is an investigational peptide with a novel dual-action mechanism … has shown promising results in early studies related to weight management and glucose regulation.' Every word of that is hedged, and FDA still treated it as evidence of intended use. The research-chemical framing does not survive contact with a webpage describing what the product does for a person.", "source": { "url": "https://www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/warning-letters/summit-research-peptides-695607-12102024", "title": "Warning Letter — Summit Research Peptides (MARCS-CMS 695607)", "publisher": "FDA", "date": "2024-12-10", "quote": "Despite statements on your product labeling marketing your products as “RESEARCH USE ONLY” and “INTENDED AS A RESEARCH CHEMICAL ONLY,” evidence obtained from your websites establish that your products are intended to be drugs for human use." }, "verifiedAt": "2026-08-02" }, { "finding": "Mazdutide appears in none of Categories 1, 2 or 3 of FDA's list of bulk drug substances nominated for use in compounding under section 503A, updated 2026-05-14.", "note": "Verified on 2026-08-02 by downloading the PDF with a browser user-agent and extracting its text locally: the string 'mazdutide' does not occur anywhere in the document, while control strings that should be present — Cesium Chloride, Ibutamoren, Kisspeptin — all are, which is what makes the absence a finding rather than a failed extraction. Recorded to close a misreading, not to assert a status, and this record deliberately carries no 503A status field as a result. Mazdutide's absence means the same thing semaglutide's does and something entirely different from BPC-157's: BPC-157 was nominated and left Category 2 when the nominators withdrew, whereas mazdutide was never in this system at all. Categorical silence is neither permission nor a safety finding.", "source": { "url": "https://www.fda.gov/media/94155/download", "title": "Bulk Drug Substances Nominated for Use in Compounding Under Section 503A of the Federal Food, Drug, and Cosmetic Act", "publisher": "FDA", "date": "2026-05-14" }, "verifiedAt": "2026-08-02" }, { "finding": "Mazdutide (Xinermei) received its first regulatory approval anywhere in China in June 2025, from China's National Medical Products Administration, for long-term body weight management in adults, and a second Chinese approval in September 2025 for glycaemic control in adults with type 2 diabetes. Neither is an FDA approval and neither has any legal effect in the United States.", "note": "Filed under FDA findings for a structural reason: this is the single fact most likely to be misread as an FDA approval, so it sits where the reader is already looking at what FDA has and has not done. It is NOT recorded in this record's fdaApproval field, which is reserved for FDA approvals and renders as one. Read the approved Chinese indication precisely, because it is narrower than the marketing: the weight-management approval is 'in combination with diet control and increased physical activity' and is gated on stated BMI thresholds, one of which additionally requires a weight-related comorbidity. SOURCING LIMIT, stated plainly: NMPA does not publish an English-language approval document at a stable citable URL, so this is carried by a peer-reviewed Adis drug-development review rather than by the regulator's own document — a weaker link than every FDA citation on this record, and recorded as such rather than dressed up. The sponsor's own press releases report the same two approvals and the same dates.", "source": { "url": "https://pubmed.ncbi.nlm.nih.gov/41028652/", "title": "Mazdutide: First Approval", "publisher": "Drugs", "date": "2025-09-30", "quote": "In June 2025, mazdutide received its first approval, in China, for use (in combination with diet control and increased physical activity) in long-term body weight management in adults with a body-mass index (BMI) of ≥ 28 kg/m2 or with a BMI ≥ 24 kg/m2 together with one or more weight-related comorbidity. Subsequently, in September 2025, mazdutide also received approval in China for use in glycaemic control in adults with T2D." }, "verifiedAt": "2026-08-02" } ], "safetySignals": [ { "signal": "In the Phase 3 GLORY-2 trial, investigators reported that the most common adverse events in the mazdutide group were vomiting (53.1%, versus 1.3% with placebo), nausea (46.9% versus 3.2%) and diarrhea (39.4% versus 6.5%), that most adverse events were mild to moderate in severity, and that adverse events leading to study treatment discontinuation occurred in 2.9% of the mazdutide group versus 0% of the placebo group.", "note": "Attributed to the trial and scoped to it. Recorded prominently because 'well tolerated' is doing heavy lifting in how this compound is marketed, and the trial's own numbers do not read that way: more than half the participants receiving mazdutide vomited. The trial's authors put it in the conclusion themselves — participants receiving the drug 'experienced gastrointestinal adverse reactions compared with those receiving placebo'. Two limits bound this. These rates come from a monitored trial in which the strength was assigned and escalation supervised, a condition that does not exist outside a trial. And 461 participants over 60 weeks cannot characterise uncommon or long-latency harms.", "source": { "url": "https://pubmed.ncbi.nlm.nih.gov/42251595/", "title": "Treatment With 9-mg Mazdutide for Weight Reduction in Chinese Adults With Obesity: The GLORY-2 Randomized Clinical Trial", "publisher": "JAMA", "date": "2026-06-07", "quote": "Adverse events leading to study treatment discontinuation were reported in 2.9% of participants in the mazdutide group compared with 0% in the placebo group. The most common adverse events were vomiting (53.1% in the mazdutide group vs 1.3% in the placebo group), nausea (46.9% vs 3.2%, respectively), and diarrhea (39.4% vs 6.5%); most of the adverse events were mild to moderate in severity." }, "verifiedAt": "2026-08-02" }, { "signal": "In the Phase 3 GLORY-1 trial, investigators reported that the most frequently reported adverse events were gastrointestinal and mostly mild to moderate in severity, and that adverse events leading to discontinuation of the trial regimen occurred in 1.5% and 0.5% of the two mazdutide groups versus 1.0% of the placebo group.", "note": "Recorded beside GLORY-2 rather than in place of it, because the two trials characterise tolerability very differently and a reader shown only one would be misled. GLORY-1 reports discontinuation rates at or below placebo; GLORY-2 reports vomiting in a majority of participants. The trials are not directly comparable — different strengths, different entry BMI, 48 weeks against 60 — and this record does not adjudicate between them. The per-group strengths behind the two discontinuation figures are elided under this site's no-dosing policy; no finding depends on them.", "source": { "url": "https://pubmed.ncbi.nlm.nih.gov/40421736/", "title": "Once-Weekly Mazdutide in Chinese Adults with Obesity or Overweight", "publisher": "The New England Journal of Medicine", "date": "2025-06-12", "quote": "The most frequently reported adverse events were gastrointestinal and mostly mild to moderate in severity." }, "verifiedAt": "2026-08-02" }, { "signal": "FDA has stated that products such as those sold as 'Mazdutide' are especially concerning from a public health perspective because injectable drug products can pose risks of serious harm to users, being delivered directly into the body and bypassing some of the body's key defenses against toxins and microorganisms.", "note": "The signal that applies to the way people actually obtain mazdutide in the United States. It is a finding about the dosage form and the supply, not about the molecule: the published trials cannot speak to it either way, because those trials used the sponsors' investigational material rather than a vial bought from a website. WHAT IS NOT CLAIMED HERE: this record found no FDA adverse-event count, import alert or counterfeit finding naming mazdutide specifically, and none is asserted. FDA publishes such figures for compounded semaglutide and tirzepatide; it has not published a comparable figure for mazdutide, and importing one would attribute to this compound what FDA wrote about others.", "source": { "url": "https://www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/warning-letters/prime-sciences-721805-03312026", "title": "Warning Letter — Prime Sciences (MARCS-CMS 721805)", "publisher": "FDA", "date": "2026-03-31", "quote": "These products are especially concerning from a public health perspective because injectable drug products can pose risks of serious harm to users. Injectable products are delivered directly into the body, sometimes directly into the bloodstream, and therefore, bypass some of the body's key defenses against toxins and microorganisms that can lead to serious and life-threatening conditions." }, "verifiedAt": "2026-08-02" } ], "faqs": [ { "question": "Is mazdutide FDA-approved?", "answer": "No. Mazdutide is not approved by FDA for any indication, in any population, by any route. In a warning letter dated 31 March 2026, FDA found that products offered for sale as 'Mazdutide' by a US website are unapproved new drugs under section 505(a) of the Federal Food, Drug, and Cosmetic Act, stating that 'No approved applications pursuant to section 505 of the FD&C Act, 21 U.S.C. 355, are in effect for these products' and that introducing or delivering them for introduction into interstate commerce violates sections 301(d) and 505(a). Seven separate queries against FDA's Drugs@FDA database on 2 August 2026 — by generic name, substance name, brand name, active-ingredient name and free text — returned no application for mazdutide. Mazdutide is approved in China, which is a different question with a different answer and no effect on US law.", "source": { "url": "https://www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/warning-letters/prime-sciences-721805-03312026", "title": "Warning Letter — Prime Sciences (MARCS-CMS 721805)", "publisher": "FDA", "date": "2026-03-31", "quote": "No approved applications pursuant to section 505 of the FD&C Act, 21 U.S.C. 355, are in effect for these products. Accordingly, these products are unapproved new drugs." }, "verifiedAt": "2026-08-02" }, { "question": "Is mazdutide approved anywhere in the world?", "answer": "Yes — in China. China's National Medical Products Administration approved mazdutide, marketed there as Xinermei, in June 2025 'for use (in combination with diet control and increased physical activity) in long-term body weight management in adults with a body-mass index (BMI) of ≥ 28 kg/m2 or with a BMI ≥ 24 kg/m2 together with one or more weight-related comorbidity', and again in September 2025 'for use in glycaemic control in adults with T2D'. That was mazdutide's first approval anywhere. Two things follow that people routinely get wrong. A Chinese approval is not an FDA approval and carries no legal effect in the United States, where FDA has found products sold as mazdutide to be unapproved new drugs. And the approved Chinese indication is narrower than the marketing that surrounds it: it is conditioned on diet control and increased physical activity, and gated on stated BMI thresholds.", "source": { "url": "https://pubmed.ncbi.nlm.nih.gov/41028652/", "title": "Mazdutide: First Approval", "publisher": "Drugs", "date": "2025-09-30", "quote": "In June 2025, mazdutide received its first approval, in China, for use (in combination with diet control and increased physical activity) in long-term body weight management in adults with a body-mass index (BMI) of ≥ 28 kg/m2 or with a BMI ≥ 24 kg/m2 together with one or more weight-related comorbidity." }, "verifiedAt": "2026-08-02" }, { "question": "Is it legal to buy mazdutide online as a research peptide?", "answer": "No. FDA has held twice that labelling mazdutide as a research chemical does not make selling it lawful, because intended use is established from the seller's own marketing rather than from its disclaimer. In a warning letter of 31 March 2026, FDA found that 'Despite statements on your product labeling marketing your products for “laboratory research purposes only” and “not for human consumption, medical use or veterinary use,” evidence obtained from your website establishes that your products are intended to be drugs for human use' — making them unapproved new drugs whose introduction into interstate commerce violates sections 301(d) and 505(a) of the Federal Food, Drug, and Cosmetic Act. FDA had made the same finding against a different mazdutide seller on 10 December 2024, over 'RESEARCH USE ONLY' and 'INTENDED AS A RESEARCH CHEMICAL ONLY' labelling. In the 2026 letter FDA cited the seller's own summary of the published GLORY-1 trial as part of the evidence of intended use, so quoting real trial results on a product page is not a defence — in that letter it was the exhibit.", "source": { "url": "https://www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/warning-letters/prime-sciences-721805-03312026", "title": "Warning Letter — Prime Sciences (MARCS-CMS 721805)", "publisher": "FDA", "date": "2026-03-31", "quote": "Despite statements on your product labeling marketing your products for “laboratory research purposes only” and “not for human consumption, medical use or veterinary use,” evidence obtained from your website establishes that your products are intended to be drugs for human use." }, "verifiedAt": "2026-08-02" }, { "question": "Does mazdutide actually work for weight loss?", "answer": "In two published Phase 3 randomised trials in Chinese adults, yes — on body weight, over 48 to 60 weeks. In GLORY-2 (NCT06164873), a double-blind placebo-controlled trial at 27 hospitals reported in JAMA on 7 June 2026, 461 Chinese adults with obesity received treatment and investigators reported a mean percentage change in body weight from baseline at week 60 of -16.65% in the mazdutide group against -1.50% in the placebo group, with 84.3% versus 33.1% of participants achieving a reduction of at least 5%. In GLORY-1 (NCT05607680), reported in the New England Journal of Medicine in June 2025, investigators randomly assigned 610 Chinese adults with obesity or overweight and reported mean body-weight changes at week 32 of -10.09% and -12.55% in the two mazdutide groups against +0.45% with placebo. Read the boundaries of that evidence. Both trials enrolled Chinese adults in China and were funded by Innovent Biologics; the registered US trials of mazdutide are Phase 2; no cardiovascular or kidney outcomes trial of mazdutide has reported; and gastrointestinal adverse events were common, with the JAMA authors concluding that participants receiving the drug 'experienced gastrointestinal adverse reactions compared with those receiving placebo'. None of it describes a vial bought from a research-peptide vendor, which was not what these trials administered.", "source": { "url": "https://pubmed.ncbi.nlm.nih.gov/42251595/", "title": "Treatment With 9-mg Mazdutide for Weight Reduction in Chinese Adults With Obesity: The GLORY-2 Randomized Clinical Trial", "publisher": "JAMA", "date": "2026-06-07", "quote": "At week 60, the mean percentage change in body weight from baseline was -16.65% (95% CI, -18.19% to -15.12%) in the mazdutide group compared with -1.50% (95% CI, -3.43% to 0.43%) in the placebo group (between-group difference, -15.15% [95% CI, -17.22% to -13.09%]; P < .001)." }, "verifiedAt": "2026-08-02" }, { "question": "Is mazdutide being tested in the United States?", "answer": "Yes, at Phase 2. Eli Lilly and Company has run registered mazdutide trials at US sites: NCT06124807, a Phase 2 double-blind trial of LY3305677 (mazdutide) against placebo for weight management at 29 US sites, which enrolled 179 participants, completed on 9 July 2025 and has results posted on ClinicalTrials.gov; and NCT06817356, a Phase 2 proof-of-concept trial in alcohol use disorder at 25 US sites, which enrolled 308 participants and completed on 19 May 2026. Lilly's CWMM master protocol NCT06143956 was recruiting at 54 sites in the United States and Argentina as of 2 August 2026 with LY3305677 listed among its interventions. Two limits on what that means. Every Phase 3 trial of mazdutide located for this record is registered by Innovent Biologics and conducted in China, so there is no US Phase 3 programme on the registry; and a trial being registered, recruiting or completed says nothing about whether or when FDA will approve anything. Trial registrations on ClinicalTrials.gov are self-reported and are not vetted before they appear.", "source": { "url": "https://clinicaltrials.gov/study/NCT06124807", "title": "A Phase 2, Parallel-Group, Double-Blind, 4-Arm Study to Investigate Weight Management With LY3305677 Compared With Placebo and in Adult Participants With Obesity or Overweight", "publisher": "ClinicalTrials.gov", "date": "2025-07-09" }, "verifiedAt": "2026-08-02" }, { "question": "Can a compounding pharmacy make mazdutide in the US?", "answer": "Mazdutide appears nowhere in FDA's list of bulk drug substances nominated for use in compounding under section 503A — not in Category 1, not Category 2, not Category 3 — as verified against the version of that document updated 14 May 2026. It is also not an active ingredient in any FDA-approved drug product: seven Drugs@FDA queries on 2 August 2026 returned no application for it. Those are the two documents that answer this question, and here is the honest limit of what they show. This record located no FDA letter, notice or guidance addressing compounding with mazdutide by name, of the kind FDA published for retatrutide in March 2025, so no mazdutide-specific FDA compounding determination is asserted here. Absence from the 503A list is not permission, and it is not a safety finding — it means mazdutide was never part of that evaluation at all.", "source": { "url": "https://www.fda.gov/media/94155/download", "title": "Bulk Drug Substances Nominated for Use in Compounding Under Section 503A of the Federal Food, Drug, and Cosmetic Act", "publisher": "FDA", "date": "2026-05-14" }, "verifiedAt": "2026-08-02" } ] }, { "slug": "melanotan-2", "name": "Melanotan II", "aliases": [ "Melanotan 2", "Melanotan-II", "MT-II", "MT2", "MII", "Melanotan II acetate", "the Barbie drug" ], "url": "https://peptides101.com/compounds/melanotan-2", "moleculeNote": "A synthetic cyclic analogue of alpha-melanocyte stimulating hormone (alpha-MSH). Dorr et al. 1996 give its structure as the lactam-bridged heptapeptide Ac-Nle4-Asp5-His6-D-Phe7-Arg8-Trp9-Lys10 alpha-MSH4-10-NH2. TWO SEPARATIONS MATTER AND BOTH ARE ROUTINELY COLLAPSED. First, Melanotan II is not afamelanotide: afamelanotide is a thirteen-amino-acid peptide (Ac-Ser-Tyr-Ser-Nle-Glu-His-(D)Phe-Arg-Trp-Gly-Lys-Pro-Val-NH2 per the SCENESSE label), it is FDA-approved under NDA 210797, and it is a different molecule under a different application. Sellers calling Melanotan II 'Melanotan 1's successor' are trading on that approval. Second, Melanotan II is not bremelanotide: the Melanotan II structure above terminates in a C-terminal amide, while the VYLEESI label gives bremelanotide as Ac-Nle-cyclo-(Asp-His-D-Phe-Arg-Trp-Lys-OH), the free acid. We state the structural difference because both structures are in primary documents and can be compared. We do NOT assert the widely repeated claim that bremelanotide is a metabolite or derivative of Melanotan II — no primary document on this record says so, and the PT-141 record declines the same claim for the same reason.", "quickAnswer": "Melanotan II is not an FDA-approved drug for any indication and never has been — Drugs@FDA returns no application for melanotan under any name — and FDA has stated in a final Federal Register order, 81 FR 79501, that Melanotan II is 'an unapproved new drug', an order permanently debarring the owner of a company that advertised it as an injectable tanning product following two federal felony conspiracy convictions. Melanotan II is also absent from FDA's 503A bulk drug substances list, so it may not lawfully be used in pharmacy compounding under section 503A; FDA lists it instead among bulk drug substances nominated but withdrawn, where FDA writes that 'Published case reports discuss serious adverse events including melanoma, posterior reversible encephalopathy syndrome, sympathomimetic toxidrome and priapism.'", "fdaStatus": { "value": "not-approved", "note": "Not approved by FDA for any indication, and never has been — Drugs@FDA returns no application for melanotan under a generic name, an active-ingredient name, or a full-text search (see fdaFindings). NOT INVESTIGATIONAL, and the distinction is the whole of the difference between this record and a drug in development. The vocabulary here requires active development by an identifiable sponsor with registered trials. Exactly one trial of Melanotan II is registered anywhere — NCT07437560 — and its own brief summary opens 'This example interventional study record describes …'. A record that identifies itself as an example is not a development programme. The genuine human studies on this record are from the 1990s and nothing followed them; a programme that stopped is not a programme that is running. Note also what 'not approved' does not settle. It says nothing about whether Melanotan II is sold — it is sold widely — and it is not the whole of the legal exposure either. FDA's position, litigated to a federal conviction, is that selling it as an unapproved new drug violated the FD&C Act, and FDA told the seller in writing that unapproved new drugs do not qualify for export either.", "source": { "url": "https://www.federalregister.gov/documents/2016/11/14/2016-27244/edward-manookian-also-known-as-ed-manning-debarment-order", "title": "Edward Manookian (Also Known as Ed Manning): Debarment Order, 81 FR 79501 (Docket No. FDA-2015-N-4169)", "publisher": "Federal Register (U.S. Food and Drug Administration)", "date": "2016-11-14", "quote": "Mr. Manookian's company advertised MII, an unapproved new drug, as an injectable tanning product through an internet Web site." }, "verifiedAt": "2026-08-02" }, "compoundingStatus": { "value": "withdrawn-from-nomination", "note": "The nominator withdrew; FDA did not clear anything. Melanotan II is absent from all three categories of the 503A bulk drug substances list (updated 2026-05-14), which was fetched with a browser user-agent and text-extracted on 2026-08-02 — a search of the full extracted text returns zero hits for 'melanotan' in any form. A bulk drug substance that is neither the subject of a USP monograph nor a component of an approved drug product must appear on that list to be used in 503A compounding. Melanotan II does not appear on it, so it may not lawfully be used in 503A compounding. AND THE WITHDRAWAL DID NOT REMOVE FDA'S CONCERNS — FDA published them on the same page, under the same table, and has never taken them down. See fdaFindings for the verbatim text.", "source": { "url": "https://www.fda.gov/drugs/human-drug-compounding/certain-bulk-drug-substances-use-compounding-may-present-significant-safety-risks", "title": "Certain Bulk Drug Substances for Use in Compounding that May Present Significant Safety Risks", "publisher": "FDA", "date": "2026-04-22", "quote": "Bulk drug substances nominated but withdrawn — This list of bulk drug substances previously in category 2 of the interim policies were withdrawn by the nominators." }, "verifiedAt": "2026-08-02" }, "evidence": { "tier": "promising-but-unproven", "humanAdministrationChecked": true, "note": "ADMINISTRATION CHECK RUN AND PASSED, and it is the reason this record does not read like the rest of the library. Three studies were opened individually on 2026-08-02 (PubMed abstracts, not full texts — we say which, because the distinction is exactly the kind we hold others to). All three are interventional and all three administered Melanotan II to human subjects by subcutaneous injection: Dorr et al. 1996, a single-blind, placebo-controlled pilot phase-I study in 3 normal male volunteers; Wessells et al. 1998, a double-blind, placebo-controlled crossover study in 10 men with psychogenic erectile dysfunction; and Wessells et al. 2000, a double-blind, placebo-controlled crossover study in 10 men with organic risk factors. None measures an endogenous peptide as a biomarker — the failure mode that reduces MOTS-c's and TB-500's apparent human counts to zero. THE TIER LABEL IS THE FLOOR, NOT THE FINDING. Read three things against it. (1) SCALE. The entire human record for this compound is 23 subjects across three studies, all at one institution, all published between 1996 and 2000. Nothing has been added in the quarter-century since, and 'promising-but-unproven' is the tier the vocabulary reserves for programmes with a human signal that were tested and never established, explicitly including ones that stopped. This one stopped. (2) THE ENDPOINT MISMATCH, which is the part that matters commercially. The two placebo-controlled crossover studies measured ERECTIONS, not tanning: Wessells 1998 reported a mean duration of tip rigidity greater than 80% of 38.0 minutes with Melanotan-II versus 3.0 with placebo (p=0.0045), and Wessells 2000 reported 45.3 minutes versus 1.9 (p=0.047). The tanning claim — the use Melanotan II is overwhelmingly sold for — rests on Dorr 1996, in which increased facial, upper-body and buttock pigmentation was reported in 2 of the 3 volunteers. That is the whole of the controlled human evidence for the effect people buy it for: an open pilot in three men. (3) TOLERABILITY WAS A FINDING, NOT A FOOTNOTE. Wessells 2000 reported that 4 of 19 Melanotan II injections were associated with severe nausea, in a supervised trial setting. None of this establishes efficacy for anything, and none of it was generated under the conditions people now buy the compound in.", "source": { "url": "https://pubmed.ncbi.nlm.nih.gov/9679884/", "title": "Synthetic melanotropic peptide initiates erections in men with psychogenic erectile dysfunction: double-blind, placebo controlled crossover study (Wessells H, Fuciarelli K, Hansen J, Hadley ME, Hruby VJ, Dorr R, Levine N; The Journal of Urology 1998;160(2):389-93)", "publisher": "PubMed", "date": "1998-08-01", "quote": "Ten men with erectile dysfunction of no known organic cause were entered in a double-blind, placebo controlled crossover study in which the erectogenic properties of Melanotan-II and a vehicle placebo were compared using real-time RigiScan monitoring." }, "verifiedAt": "2026-08-02" }, "fdaApproval": null, "fdaFindings": [ { "finding": "FDA states, in a final Federal Register order, that Melanotan II was advertised as an injectable tanning product and that it is an unapproved new drug. The order permanently debars the seller's owner following two federal felony conspiracy convictions.", "note": "This is the single most citable document on the record and it is not a press release, a prosecution announcement or a news story — it is FDA's own final order, published at 81 FR 79501 on 14 November 2016, effective the same day, under Docket No. FDA-2015-N-4169. The order recites the underlying judgment: on 28 August 2015 the U.S. District Court for the Middle District of Tennessee entered judgment against Edward Manookian, President and owner of Melanocorp, Inc., for two counts of conspiracy to commit an offense against the United States in violation of 18 U.S.C. 371. FDA's characterisation of the conduct is quoted here in full because it is the agency's, not ours: 'Mr. Manookian knowingly sold unapproved drugs and put patients at risk.' Two details are worth keeping. First, FDA sent a warning letter on or about 30 August 2007, the company told FDA it had stopped U.S. sales, and shipments continued anyway — the conviction is for the conspiracy to defraud that followed, not for the original sales. Second, the order records that the Melanocorp website 'also advertised MII as being 100 percent U.S. made, whereas in fact some of the MII sold by Melanocorp was manufactured in and imported from China.' A provenance claim on a seller's website is a marketing statement, and in the one case where a court examined one it was false.", "source": { "url": "https://www.federalregister.gov/documents/2016/11/14/2016-27244/edward-manookian-also-known-as-ed-manning-debarment-order", "title": "Edward Manookian (Also Known as Ed Manning): Debarment Order, 81 FR 79501 (Docket No. FDA-2015-N-4169)", "publisher": "Federal Register (U.S. Food and Drug Administration)", "date": "2016-11-14", "quote": "Melanotan II (MII) was a peptide, or series of amino acids, that was marketed, sold, and shipped by Melanocorp to customers in the United States and abroad. Mr. Manookian's company advertised MII, an unapproved new drug, as an injectable tanning product through an internet Web site." }, "verifiedAt": "2026-08-02" }, { "finding": "FDA published its own safety concerns for Melanotan II, in FDA's words: a risk of immunogenicity for certain routes of administration, and published case reports of serious adverse events including melanoma, posterior reversible encephalopathy syndrome, sympathomimetic toxidrome and priapism.", "note": "THIS ENTRY IS THE OUTLIER OF THE PAGE IT SITS ON, and the comparison is checkable: both tables were extracted on 2026-08-02, and Melanotan II is the ONLY substance anywhere on that page for which FDA writes the words melanoma, posterior reversible encephalopathy syndrome, sympathomimetic toxidrome or priapism. Its sixteen table-mates read the other way — KPV and MOTS-c get 'FDA has not identified any human exposure data', BPC-157 gets 'no, or only limited, safety-related information'. Melanotan II is not on this list because FDA knows nothing about it. It is on the list partly because of what has been reported. The withdrawal changes none of this. FDA left the entry standing after the nomination was withdrawn, which forecloses the reading — the one this site exists to correct — that leaving Category 2 means the concerns were resolved.", "source": { "url": "https://www.fda.gov/drugs/human-drug-compounding/certain-bulk-drug-substances-use-compounding-may-present-significant-safety-risks", "title": "Certain Bulk Drug Substances for Use in Compounding that May Present Significant Safety Risks", "publisher": "FDA", "date": "2026-04-22", "quote": "Compounded drugs containing Melanotan II may pose risk for immunogenicity for certain routes of administration due to the potential for aggregation or peptide-related impurities. Published case reports discuss serious adverse events including melanoma, posterior reversible encephalopathy syndrome, sympathomimetic toxidrome and priapism." }, "verifiedAt": "2026-08-02" }, { "finding": "Drugs@FDA contains no application for melanotan under any name. Queried on 2026-08-02 by generic name, by active-ingredient name, and by unfielded full-text search, all returning NOT_FOUND; the drug label endpoint returns NOT_FOUND as well.", "note": "Recorded with the queries stated because a NOT_FOUND is only as good as the field it was asked of. openFDA's `openfda` blocks are sometimes empty, and this library has already shipped one false 'not in Drugs@FDA' claim that was an artifact of querying a single field. Both fields were tried, plus a bare full-text search across the whole database, plus the label endpoint. The same query shapes return NDA210797 for afamelanotide on the first attempt, so the absence is the database's, not the query's. openFDA reported meta.last_updated 2026-07-31 at the time of the check. Re-run the URL to re-verify; it is a live query, not a PDF.", "source": { "url": "https://api.fda.gov/drug/drugsfda.json?search=openfda.generic_name:\"melanotan\"+OR+products.active_ingredients.name:\"MELANOTAN+II\"&limit=5", "title": "Drugs@FDA — approved drug products database, queried for melanotan (openFDA)", "publisher": "FDA", "date": "2026-08-02", "quote": "{ \"error\": { \"code\": \"NOT_FOUND\", \"message\": \"No matches found!\" } }" }, "verifiedAt": "2026-08-02" }, { "finding": "Melanotan II appears nowhere in Categories 1, 2 or 3 of FDA's 503A bulk drug substances list, updated 2026-05-14.", "note": "Verified by fetching the PDF with a browser user-agent and extracting all seven pages locally on 2026-08-02: a case-insensitive search of the full text returns zero hits for 'melanotan'. Read this absence the way BPC-157's is read, not the way bremelanotide's is: Melanotan II is not the active ingredient of any approved drug product, so the 503A nomination pathway WAS the relevant one for it, it was on that pathway, and it left by withdrawal. Absence from the list means it may not lawfully be used in 503A compounding.", "source": { "url": "https://www.fda.gov/media/94155/download", "title": "Bulk Drug Substances Nominated for Use in Compounding Under Section 503A of the Federal Food, Drug, and Cosmetic Act", "publisher": "FDA", "date": "2026-05-14" }, "verifiedAt": "2026-08-02" }, { "finding": "Melanotan II was not among the seven bulk drug substances the Pharmacy Compounding Advisory Committee considered at its meeting of 23-24 July 2026, and received no committee review or recommendation.", "note": "Stated because the inference readers will make is wrong in a specific and predictable way. Melanotan II sits in the same 'nominated but withdrawn' table as BPC-157, TB-500, KPV, MOTS-c, semax, epitalon and emideltide, six of which the committee voted to recommend for the 503A list in July 2026. The agenda was fetched and text-extracted on 2026-08-02 and returns zero hits for 'melanotan': the substances heard were BPC-157-related, KPV-related, TB-500-related, MOTS-c-related, semax-related, epitalon-related and emideltide-related bulk drug substances, and no others. So the 'FDA panel backs the peptides' coverage does not reach Melanotan II at all — there was no vote about it, favourable or otherwise. Separately, and for the six it does reach, a committee recommendation is non-binding and did not change the list.", "source": { "url": "https://www.fda.gov/media/193771/download", "title": "Pharmacy Compounding Advisory Committee Meeting, July 23-24, 2026 — Agenda", "publisher": "FDA", "date": "2026-07-23" }, "verifiedAt": "2026-08-02" }, { "finding": "FDA told the seller in writing that unapproved new drugs do not qualify for export, after the seller took the position that it could lawfully export Melanotan II regardless of that status.", "note": "A failed legal theory, recorded as a failed one. The export argument sits beside research-use-only labelling in the same family of workarounds this market relies on: an assertion about paperwork offered against a status that turns on the product itself. FDA rejected it in writing at the time, the order records that shipments continued anyway, and the sequence ended in a federal conviction and permanent debarment.", "source": { "url": "https://www.federalregister.gov/documents/2016/11/14/2016-27244/edward-manookian-also-known-as-ed-manning-debarment-order", "title": "Edward Manookian (Also Known as Ed Manning): Debarment Order, 81 FR 79501 (Docket No. FDA-2015-N-4169)", "publisher": "Federal Register (U.S. Food and Drug Administration)", "date": "2016-11-14", "quote": "On or about December 28, 2007, FDA sent a letter to Mr. Manookian's attorney which reiterated that unapproved new drugs do not qualify for export." }, "verifiedAt": "2026-08-02" }, { "finding": "The only registered clinical trial of Melanotan II anywhere describes itself in its own brief summary as an example study record, states that it is not an FDA-regulated drug study, and has posted no results.", "note": "Retrieved from the ClinicalTrials.gov v2 API on 2026-08-02 and read field by field, because this is the registration a vendor will cite as proof that Melanotan II is 'in Phase 2 trials'. On its face it is impressive: randomized, quadruple-masked, parallel-group, placebo-controlled, 60 estimated participants. Every contamination marker this library has catalogued is also present. Its own summary calls it an example record. Its oversight module reports isFdaRegulatedDrug: false. Its actual start date is 2026-02-02 and it has been RECRUITING since, with no results and an estimated — not actual — enrolment. Its lead sponsor, an industry entity named Hudson Biotech, lists contacts at a beijing-biotech.com domain against a hospital site in Shenzhen. Registration is self-reported and nobody vets it before it appears. This is not evidence, and it is not a development programme.", "source": { "url": "https://clinicaltrials.gov/study/NCT07437560", "title": "NCT07437560 — A Randomized, Double-Blind, Placebo-Controlled Phase 2 Study of Melanotan II … in Adults With Stable Nonsegmental Vitiligo", "publisher": "ClinicalTrials.gov", "date": "2026-02-27", "quote": "This example interventional study record describes a randomized Phase 2 clinical trial evaluating investigational Melanotan II (MT-II) as an adjunct to standard NB-UVB phototherapy for repigmentation in adults with stable nonsegmental vitiligo." }, "verifiedAt": "2026-08-02" } ], "safetySignals": [ { "signal": "Clinicians reported a case of systemic toxicity with sympathomimetic excess, rhabdomyolysis and renal dysfunction after subcutaneous self-injection of Melanotan II bought over the internet, requiring intensive-care admission.", "note": "The detail that makes this case unusually hard to dismiss is analytical, not clinical. The authors report that the injected substance 'was analyzed via mass spectrometry and was confirmed to be Melanotan II when compared with an industry purchased standard sample'. The standard defence for a grey-market adverse event — that the vial contained something else — was tested here and did not hold. The reported course was tachycardia, mydriasis, diaphoresis and diffuse muscle tremors on presentation, a creatine phosphokinase that rose roughly tenfold over the following 12 hours, and discharge from the ICU after 3 days. A single case report establishes a possible association, not a rate.", "source": { "url": "https://pubmed.ncbi.nlm.nih.gov/23121206/", "title": "Melanotan II injection resulting in systemic toxicity and rhabdomyolysis (Nelson ME, Bryant SM, Aks SE; Clinical Toxicology 2012;50(10):1169-73)", "publisher": "PubMed", "date": "2012-12-01", "quote": "Melanotan II use resulted in systemic toxicity including apparent sympathomimetic symptoms, rhabdomyolysis, and renal dysfunction." }, "verifiedAt": "2026-08-02" }, { "signal": "Urologists reported a case of acute low-flow priapism after subcutaneous abdominal injection of melanotan, managed with cavernosal aspiration, irrigation and intracavernosal phenylephrine; the patient had not recovered erectile function at four-week follow-up.", "note": "Read this against the evidence section rather than apart from it. The only placebo-controlled human studies of Melanotan II were erection studies, and the erectogenic effect they measured is the same pharmacology that produces this. The authors' own framing is that any 'future therapeutic application of these agents will need to take this potential life altering complication into consideration'. Low-flow priapism is a time-critical urological emergency; the mechanism working harder than intended is not a different event from the mechanism working.", "source": { "url": "https://pubmed.ncbi.nlm.nih.gov/30796078/", "title": "Melanotan-induced priapism: a hard-earned tan (Dreyer BA, Amer T, Fraser M; BMJ Case Reports 2019;12(2):e227644)", "publisher": "PubMed", "date": "2019-02-21", "quote": "The patient avoided requiring surgical shunting but had not yet recovered erectile function at 4-week follow-up." }, "verifiedAt": "2026-08-02" }, { "signal": "Physicians reported a case of posterior reversible encephalopathy syndrome associated with melanotan in the Annals of Internal Medicine — one of the four serious adverse events FDA names for Melanotan II on its own safety-risks page.", "note": "Cited by title and journal only. The record is a brief correspondence item and its abstract is not indexed in PubMed, so nothing is quoted from it here and no clinical detail is asserted beyond what the title carries — which is the honest limit of what was actually opened. It is recorded because it is one of the published case reports FDA's safety text points at, and because posterior reversible encephalopathy syndrome is a neurological emergency that no one buying a tanning product is watching for.", "source": { "url": "https://pubmed.ncbi.nlm.nih.gov/23648958/", "title": "Melanotan and the posterior reversible encephalopathy syndrome (Kaski D, Stafford N, Mehta A, Jenkins IH, Malhotra P; Annals of Internal Medicine 2013;158(9):707-8)", "publisher": "PubMed", "date": "2013-05-07" }, "verifiedAt": "2026-08-02" }, { "signal": "Dermatologists have reported melanoma and melanoma in situ arising in melanotan users, alongside a wider case literature on eruptive and dysplastic naevi and darkening of pre-existing naevi following melanotan injection.", "note": "STATE THE LIMIT PLAINLY: these are case reports, and case reports establish association and temporal sequence, not causation. Nobody has run the study that would settle it, and given the compound's legal status nobody will. Two things keep this on the record anyway. FDA itself lists melanoma first among the serious adverse events in published case reports for Melanotan II. And the confounding runs toward the compound rather than away from it — melanotan is used to tan, users typically also use ultraviolet exposure, and the case series repeatedly describe both together. A related 2011 report in the British Journal of Dermatology is titled 'Melanotan-associated melanoma'. The claim a seller makes — that an injected tan is the safer tan — is the one claim this literature bears on, and it does not support it.", "source": { "url": "https://pubmed.ncbi.nlm.nih.gov/22724573/", "title": "Melanotan-associated melanoma in situ (Ong S, Bowling J; Australasian Journal of Dermatology 2012;53(4):301-2)", "publisher": "PubMed", "date": "2012-11-01", "quote": "Injectable synthetic melanotropic peptides (often called melanotan) to enhance tanning are available over the Internet despite being unlicensed compounds with an unproven safety record. There have been reports of dysplastic naevi and melanoma associated with the use of melanotropic peptides. We report a case of melanotan-associated melanoma in situ." }, "verifiedAt": "2026-08-02" }, { "signal": "In the studies that administered it under supervision, investigators reported nausea, stretching and yawning more frequently with Melanotan II than with placebo, with severe nausea after 4 of 19 Melanotan II injections in the 2000 crossover study.", "note": "Recorded from the compound's own trials rather than from its critics. This is the tolerability profile observed in a screened, consented, clinically supervised population of ten men. Dorr et al. 1996 similarly reported mild nausea at most levels tested and grade II somnolence and fatigue in one of two volunteers at the highest level they reached. Whatever the human record of Melanotan II shows, an uneventful one is not it.", "source": { "url": "https://pubmed.ncbi.nlm.nih.gov/11018622/", "title": "Effect of an alpha-melanocyte stimulating hormone analog on penile erection and sexual desire in men with organic erectile dysfunction (Wessells H, Gralnek D, Dorr R, Hruby VJ, Hadley ME, Levine N; Urology 2000;56(4):641-6)", "publisher": "PubMed", "date": "2000-10-01", "quote": "Nausea and stretching/yawning occurred more frequently with Melanotan II, and 4 of 19 injections were associated with severe nausea." }, "verifiedAt": "2026-08-02" }, { "signal": "A related melanocortin receptor agonist approved by FDA, bremelanotide, carries a labelled focal hyperpigmentation signal that FDA states was not confirmed to resolve in all patients after discontinuation.", "note": "READ THE SCOPE BEFORE READING THE SIGNAL. This is a finding about bremelanotide, not about Melanotan II, and it is recorded here as the closest thing that exists to a regulated safety dataset for a nonselective melanocortin agonist in humans — because for Melanotan II itself there is none. It cannot be transferred: different molecule, different application, different exposure. What makes it worth carrying is the direction of the inference. FDA's label attributes pigmentation to MC1R binding, the frequency rose sharply with more frequent use, and resolution after stopping was not confirmed in every patient. Melanotan II is bought specifically FOR pigmentation, which means it is bought by people seeking the effect that carried this signal, with no prescriber, no label and no follow-up.", "source": { "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/210557s000lbl.pdf", "title": "VYLEESI (bremelanotide) injection — Highlights of Prescribing Information, original approval", "publisher": "FDA", "date": "2019-06-21", "quote": "Resolution of the focal hyperpigmentation was not confirmed in all patients after discontinuation of VYLEESI." }, "verifiedAt": "2026-08-02" } ], "faqs": [ { "question": "Is Melanotan 2 FDA approved?", "answer": "No. Melanotan II has never been approved by FDA for any indication, and Drugs@FDA holds no application for it: queries by generic name, by active-ingredient name, and by unfielded full-text search all returned NOT_FOUND on 2 August 2026, as did the FDA drug label endpoint. FDA has stated the point directly in a final Federal Register order, describing Melanotan II as 'an unapproved new drug'. The confusion usually comes from a different molecule: afamelanotide, marketed as SCENESSE, is an FDA-approved melanocortin 1 receptor agonist under NDA 210797 — but it is a different and larger molecule, described on its own label as 'a synthetic peptide containing 13 amino acids', and that label indicates it 'to increase pain free light exposure in adult patients with a history of phototoxic reactions from erythropoietic protoporphyria (EPP)', a rare inherited disorder. An approval belonging to another molecule for another purpose is not an approval for Melanotan II.", "source": { "url": "https://api.fda.gov/drug/label.json?search=openfda.generic_name:\"afamelanotide\"&limit=1", "title": "SCENESSE (afamelanotide) implant — current Structured Product Label, via the openFDA label API", "publisher": "FDA", "date": "2026-05-11", "quote": "SCENESSE is a melanocortin 1 receptor (MC1-R) agonist indicated to increase pain free light exposure in adult patients with a history of phototoxic reactions from erythropoietic protoporphyria (EPP)" }, "verifiedAt": "2026-08-02" }, { "question": "Is Melanotan 2 legal in the US in 2026?", "answer": "No, not for sale for human use, and the answer here is unusually well documented. FDA's position is that Melanotan II is an unapproved new drug that cannot be introduced into interstate commerce without an approved application, and that position has been tested to judgment: FDA's final order at 81 FR 79501, effective 14 November 2016, permanently debars Edward Manookian, owner of Melanocorp, Inc., after the U.S. District Court for the Middle District of Tennessee entered judgment against him on two counts of conspiracy under 18 U.S.C. 371 for conduct relating to the sale of Melanotan II as an injectable tanning product. FDA also told that seller in writing that unapproved new drugs do not qualify for export. Separately, Melanotan II is absent from FDA's 503A bulk drug substances list, so it may not lawfully be used in pharmacy compounding either. Being widely available for sale online is not the same question as being lawful to sell.", "source": { "url": "https://www.federalregister.gov/documents/2016/11/14/2016-27244/edward-manookian-also-known-as-ed-manning-debarment-order", "title": "Edward Manookian (Also Known as Ed Manning): Debarment Order, 81 FR 79501 (Docket No. FDA-2015-N-4169)", "publisher": "Federal Register (U.S. Food and Drug Administration)", "date": "2016-11-14", "quote": "On August 28, 2015, the U.S. District Court for the Middle District of Tennessee entered judgment against Mr. Manookian for two counts of conspiracy to commit an offense against the United States, in violation of 18 U.S.C. 371." }, "verifiedAt": "2026-08-02" }, { "question": "Does Melanotan 2 cause melanoma?", "answer": "Not established — and the honest answer is that the study which would settle it has never been done. What exists is a case literature, and FDA points at it: on its own safety-risks page FDA writes that 'Published case reports discuss serious adverse events including melanoma, posterior reversible encephalopathy syndrome, sympathomimetic toxidrome and priapism' for Melanotan II. Dermatologists have published cases of melanoma and melanoma in situ in melanotan users, together with reports of eruptive and dysplastic naevi and darkening of pre-existing moles after injection. Case reports establish association and sequence, not causation, and most users of injectable melanotropic peptides also use ultraviolet exposure, which confounds any single case. What the literature does bear on is the specific claim these products are sold with — that an injected tan is a safer tan — and it does not support it.", "source": { "url": "https://www.fda.gov/drugs/human-drug-compounding/certain-bulk-drug-substances-use-compounding-may-present-significant-safety-risks", "title": "Certain Bulk Drug Substances for Use in Compounding that May Present Significant Safety Risks", "publisher": "FDA", "date": "2026-04-22", "quote": "Published case reports discuss serious adverse events including melanoma, posterior reversible encephalopathy syndrome, sympathomimetic toxidrome and priapism." }, "verifiedAt": "2026-08-02" }, { "question": "Are there any human clinical trials of Melanotan 2?", "answer": "Yes, but only three, all small, and all finished a quarter-century ago. Melanotan II was administered to human subjects by subcutaneous injection in a pilot phase-I study in 3 normal male volunteers reported by Dorr and colleagues in Life Sciences in 1996, and in two double-blind, placebo-controlled crossover studies at the University of Arizona reported by Wessells and colleagues in The Journal of Urology in 1998 and in Urology in 2000, each enrolling 10 men with erectile dysfunction. That is 23 subjects in total, and nothing has been added since. Note what the controlled studies measured: erections, not tanning. In the 1998 study the investigators reported a mean duration of penile tip rigidity greater than 80% of 38.0 minutes with Melanotan-II versus 3.0 minutes with placebo. The tanning effect the compound is actually sold for was reported in the 1996 pilot, in which increased pigmentation was observed in 2 of the 3 volunteers — an open study in three men. One further trial is registered on ClinicalTrials.gov, NCT07437560, but its own summary opens 'This example interventional study record describes …', it reports itself as not an FDA-regulated drug study, and it has posted no results.", "source": { "url": "https://pubmed.ncbi.nlm.nih.gov/9679884/", "title": "Synthetic melanotropic peptide initiates erections in men with psychogenic erectile dysfunction: double-blind, placebo controlled crossover study (Wessells H, Fuciarelli K, Hansen J, Hadley ME, Hruby VJ, Dorr R, Levine N; The Journal of Urology 1998;160(2):389-93)", "publisher": "PubMed", "date": "1998-08-01", "quote": "Mean duration of tip rigidity greater than 80% was 38.0 minutes with Melanotan-II and 3.0 with placebo (p=0.0045)." }, "verifiedAt": "2026-08-02" }, { "question": "Can I get Melanotan 2 from a compounding pharmacy?", "answer": "Not lawfully. Melanotan II appears in none of the three categories of FDA's 503A bulk drug substances list, updated 14 May 2026 and text-extracted directly on 2 August 2026, which returns zero hits for 'melanotan' in any form. A bulk drug substance that is neither the subject of a USP monograph nor a component of an FDA-approved drug product must appear on that list to be used in compounding under section 503A, and Melanotan II is not an ingredient of any approved product. FDA lists it instead in a table headed 'Bulk drug substances nominated but withdrawn', whose own header explains that these substances were 'previously in category 2 of the interim policies' and 'were withdrawn by the nominators'. A withdrawal by the party that nominated the substance is not a decision by FDA in the substance's favour, and it did not move Melanotan II onto the list.", "source": { "url": "https://www.fda.gov/media/94155/download", "title": "Bulk Drug Substances Nominated for Use in Compounding Under Section 503A of the Federal Food, Drug, and Cosmetic Act", "publisher": "FDA", "date": "2026-05-14" }, "verifiedAt": "2026-08-02" }, { "question": "Did the FDA advisory committee that backed BPC-157 in July 2026 also cover Melanotan 2?", "answer": "No. Melanotan II was not on the agenda of the Pharmacy Compounding Advisory Committee meeting held on 23-24 July 2026 and received no committee review, no discussion and no vote. The agenda, text-extracted on 2 August 2026, returns zero hits for 'melanotan'; the substances heard were the BPC-157-related, KPV-related, TB-500-related, MOTS-c-related, semax-related, epitalon-related and emideltide-related bulk drug substances, and no others. The overlap that causes the confusion is real but narrow: Melanotan II sits in the same FDA table of substances nominated but withdrawn as those seven. Sharing a table is not sharing a proceeding. Nothing that happened at that meeting applies to Melanotan II, and for the six substances the committee did recommend, the recommendation was non-binding and did not by itself change the 503A bulks list.", "source": { "url": "https://www.fda.gov/media/193771/download", "title": "Pharmacy Compounding Advisory Committee Meeting, July 23-24, 2026 — Agenda", "publisher": "FDA", "date": "2026-07-23" }, "verifiedAt": "2026-08-02" }, { "question": "What are the documented side effects of Melanotan 2?", "answer": "FDA names four in published case reports for Melanotan II: melanoma, posterior reversible encephalopathy syndrome, sympathomimetic toxidrome and priapism. Each is traceable to peer-reviewed case literature. Clinicians reporting in Clinical Toxicology in 2012 described a man who developed systemic toxicity with sympathomimetic excess, rhabdomyolysis and renal dysfunction after injecting Melanotan II bought over the internet, requiring intensive-care admission — and the injected material was analysed by mass spectrometry and confirmed to be Melanotan II, which rules out the usual explanation that the vial contained something else. Urologists reporting in BMJ Case Reports in 2019 described acute low-flow priapism after injection, treated with cavernosal aspiration and irrigation, in a patient who had not recovered erectile function at four-week follow-up. In the compound's own supervised trials, investigators reported nausea, stretching and yawning more often with Melanotan II than with placebo, with severe nausea after 4 of 19 injections in the 2000 study. FDA separately states that compounded drugs containing Melanotan II may pose a risk for immunogenicity for certain routes of administration.", "source": { "url": "https://pubmed.ncbi.nlm.nih.gov/23121206/", "title": "Melanotan II injection resulting in systemic toxicity and rhabdomyolysis (Nelson ME, Bryant SM, Aks SE; Clinical Toxicology 2012;50(10):1169-73)", "publisher": "PubMed", "date": "2012-12-01", "quote": "The substance, which he injected, was analyzed via mass spectrometry and was confirmed to be Melanotan II when compared with an industry purchased standard sample." }, "verifiedAt": "2026-08-02" } ] }, { "slug": "mots-c", "name": "MOTS-c", "aliases": [ "Mitochondrial Open Reading Frame of the 12S rRNA-c", "MOTS-c acetate", "MOTSc" ], "url": "https://peptides101.com/compounds/mots-c", "moleculeNote": "A mitochondrial-derived peptide of 16 amino acids, discovered in 2015. FDA evaluates two related substances: MOTS-c (free base) and MOTS-c acetate — different pharmaceutical ingredients, hence different bulk drug substances. FDA notes MOTS-c is a common name and not a USAN, and that it has encountered multiple salts and derivatives — including different active moieties — sold commercially under this same common name. DISTINGUISH FROM CB4211: CohBar's CB4211 is a modified ANALOG of MOTS-c, not MOTS-c. It is a different molecule, and its human exposure is not MOTS-c's human exposure. Conflating the two is the most likely honest error available on this compound — see the evidence note.", "quickAnswer": "MOTS-c is not on FDA's 503A bulk drug substances list, and FDA staff have proposed not adding either MOTS-c (free base) or MOTS-c acetate to it, ahead of the Pharmacy Compounding Advisory Committee meeting on 23-24 July 2026. FDA searched the published medical literature itself and identified no clinical studies and no human exposure data for MOTS-c by any route of administration; it states that potential safety risks in humans are therefore unknown, and that there is a lack of evidence to evaluate effectiveness for any of the uses MOTS-c was nominated for.", "fdaStatus": { "value": "not-approved", "note": "Not an FDA-approved drug for any indication, and not in active development toward approval. That says nothing about whether it is sold — it is.", "source": { "url": "https://www.fda.gov/media/193347/download", "title": "MOTS-c-Related Bulk Drug Substances — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, July 23-24, 2026", "publisher": "FDA", "date": "2026-07-23" }, "verifiedAt": "2026-07-16" }, "compoundingStatus": { "value": "withdrawn-from-nomination", "note": "Absent from Categories 1, 2 and 3 in the list updated 2026-05-14 — verified by fetching and text-extracting the document directly; the string 'MOTS' does not appear in it at all. Category 2 contains exactly six substances — Cesium Chloride, Domperidone, Germanium Sesquioxide, Ibutamoren Mesylate, Kisspeptin-10, and Quinacrine Hydrochloride for intrauterine administration — and MOTS-c is not one of them. Do not read that as reassurance: Category 2 is a list of substances FDA affirmatively found to raise significant safety risks, and staying off it means only that FDA has not made that finding, which on this substance is because nobody has looked in humans at all. The nomination — submitted by Wells Pharmacy Network, Document ID FDA-2015-N-3534-0293 — was withdrawn (withdrawal at Document ID FDA-2015-N-3534-0484). Withdrawal is not a legalisation event: MOTS-c did not enter Category 1, is not on the 503A bulks list, and remains non-compoundable. FDA is nonetheless evaluating both substances at its own discretion, and proposes not adding them. Category status is also not the criminal line — the Watkins indictment (D. Utah, 1:26-cr-00015, 2026-04-01) charges misbranding under 352(b), which is why Category 1 substances sit in the same indictment as non-listed ones.", "source": { "url": "https://www.fda.gov/media/193347/download", "title": "MOTS-c-Related Bulk Drug Substances — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, July 23-24, 2026", "publisher": "FDA", "date": "2026-07-23" }, "verifiedAt": "2026-07-16" }, "evidence": { "tier": "animal-or-in-vitro-only", "humanAdministrationChecked": true, "note": "Zero human administration studies of MOTS-c itself. This tier was assigned by checking what was ADMINISTERED, never by counting trials, and the count is where this compound traps people. MOTS-c appears to have several human RCTs; it has none. Spot-checked example: Nature Scientific Reports 2021 (PMC8376922), a secondary analysis of 49 breast cancer survivors in a 16-week supervised aerobic-and-resistance exercise trial, in which researchers reported that fasting plasma MOTS-c measured by in-house ELISA rose post-intervention in non-Hispanic White participants and did not change significantly in Hispanic participants. The intervention was EXERCISE; MOTS-c was the outcome measured, not the drug given. The same is true of the exercise-biomarker literature generally. FDA's own independent search agrees, and FDA characterises the nonclinical work as limited to in-vitro and in-vivo rodent models. THE NEAR-MISS, and note its source: CB4211 is an analog of MOTS-c, NOT MOTS-c. The FDA briefing document does not mention CB4211 or CohBar anywhere, so nothing in this paragraph comes from it. It comes from the ClinicalTrials.gov registry record NCT03998514 (https://clinicaltrials.gov/study/NCT03998514), which lists a Phase 1a/1b study of CB4211 in healthy non-obese subjects and subjects with nonalcoholic fatty liver disease, lead sponsor CohBar, Inc., enrollment 88 actual, overall status Completed, completion date 2021-04-19, with no results posted to the registry. That is human exposure to a DIFFERENT MOLECULE. It neither contradicts FDA's finding nor transfers to MOTS-c, and because no results were posted, the registry establishes only that the study ran and finished — not what it found. The precise statement is: no human administration data for MOTS-c; rodent and in-vitro only; one completed Phase 1, results unreported, in a related but distinct analog.", "source": { "url": "https://www.fda.gov/media/193347/download", "title": "MOTS-c-Related Bulk Drug Substances — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, July 23-24, 2026", "publisher": "FDA", "date": "2026-07-23", "quote": "We performed our own search of published medical literature and did not identify clinical studies evaluating administration of MOTS-c-related BDSs in human subjects." }, "verifiedAt": "2026-07-16" }, "fdaApproval": null, "fdaFindings": [ { "finding": "FDA staff propose not adding MOTS-c (free base) or MOTS-c acetate to the 503A Bulks List, ahead of the Pharmacy Compounding Advisory Committee meeting on 23-24 July 2026.", "note": "A staff proposal is not a final determination. The briefing document states: 'The FDA will not issue a final determination on the issues at hand until input from the advisory committee process has been considered and all reviews have been finalized.'", "source": { "url": "https://www.fda.gov/media/193347/download", "title": "MOTS-c-Related Bulk Drug Substances — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, July 23-24, 2026", "publisher": "FDA", "date": "2026-07-23", "quote": "Accordingly, we propose not adding MOTS-c (free base) or MOTS-c acetate to the 503A Bulks List." }, "verifiedAt": "2026-07-16" }, { "finding": "FDA identified no clinical studies and no human exposure data for MOTS-c via any route of administration, and concludes that potential safety risks in humans are unknown.", "note": "The single most citable line on this compound, and one no vendor-funded page will ever print. 'Unknown' is the operative word — it is neither a clean bill of health nor a finding of harm. It means nobody has looked in humans. FDA's evidence cutoff is roughly March 2025 (its FAERS searches run through 2025-03-09), so this finding is scoped to what existed then; the CB4211 analog trial completed in 2021 and does not disturb it, because CB4211 is not MOTS-c.", "source": { "url": "https://www.fda.gov/media/193347/download", "title": "MOTS-c-Related Bulk Drug Substances — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, July 23-24, 2026", "publisher": "FDA", "date": "2026-07-23", "quote": "The nomination did not include, and FDA has not identified, any clinical studies or human exposure data for MOTS-c via any route of administration. Therefore, potential safety risks associated with the use of MOTS-c-related BDSs in humans are unknown." }, "verifiedAt": "2026-07-16" }, { "finding": "FDA did not evaluate ANY of the six nominated uses — insulin resistance, obesity, osteoporosis, vascular calcification, muscle/fat metabolism, longevity — because the nomination lacked sufficient information and FDA identified no clinical studies evaluating those uses.", "note": "Read footnote 4 before repeating the common claim that FDA 'assessed MOTS-c for obesity and osteoporosis and it fell short.' FDA declined to evaluate every single proposed use. Obesity and osteoporosis appear in the document only as context — as serious conditions with existing FDA-approved therapies — never as indications FDA assessed. This is an EVIDENTIARY VACUUM, NOT A REGULATORY LOOPHOLE. Footnote 3 notes that inclusion on the 503A Bulks List may not be limited to a specific use, so a 'do not add' outcome bars MOTS-c for ALL uses. The nomination cited 12 literature references; none was a clinical study.", "source": { "url": "https://www.fda.gov/media/193347/download", "title": "MOTS-c-Related Bulk Drug Substances — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, July 23-24, 2026", "publisher": "FDA", "date": "2026-07-23", "quote": "FDA did not evaluate the proposed uses: insulin resistance, obesity, osteoporosis, vascular calcification, muscle/fat metabolism, longevity because the nomination did not include sufficient information for the Agency to evaluate whether the substance is appropriate for these uses in compounded drug products. In addition, FDA did not identify clinical studies evaluating these uses of MOTS-c." }, "verifiedAt": "2026-07-16" }, { "finding": "FDA states that neither MOTS-c nor MOTS-c acetate has an applicable USP or National Formulary drug substance monograph, and that neither is a component of an FDA-approved drug.", "note": "This sentence lives in the PCAC briefing document, NOT in the 503A bulks list — the bulks list PDF contains neither the string 'MOTS' nor the string 'monograph'. Cite it accordingly. FDA separately searched the European Pharmacopoeia (11.5 edition, 2024) and the Japanese Pharmacopoeia (18th Edition) and found no monograph listings for either substance, and found no EMA-authorized products containing them.", "source": { "url": "https://www.fda.gov/media/193347/download", "title": "MOTS-c-Related Bulk Drug Substances — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, July 23-24, 2026", "publisher": "FDA", "date": "2026-07-23", "quote": "MOTS-c and MOTS-c acetate do not have an applicable USP or NF drug substance monograph and neither is a component of an FDA-approved drug." }, "verifiedAt": "2026-07-16" }, { "finding": "FDA concludes there is a lack of evidence to evaluate the effectiveness of the MOTS-c-related bulk drug substances for the nominated uses, because the nonclinical pharmacological studies were limited to in-vitro and in-vivo rodent models, dose-response assessments are missing, and the molecular targets are unknown.", "note": "Distinct from a finding of ineffectiveness, and the distinction is the whole point. FDA is not saying the MOTS-c-related BDSs failed; it is saying there is nothing to grade. Pair it with the fact that FDA declined to evaluate the six proposed uses at all — the effectiveness question was never reached because the evidence to reach it does not exist.", "source": { "url": "https://www.fda.gov/media/193347/download", "title": "MOTS-c-Related Bulk Drug Substances — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, July 23-24, 2026", "publisher": "FDA", "date": "2026-07-23", "quote": "There is a lack of evidence to evaluate the effectiveness of the MOTS-c-related BDSs for the nominated uses." }, "verifiedAt": "2026-07-16" }, { "finding": "FDA considers both MOTS-c (free base) and MOTS-c acetate NOT well-characterized physically and chemically, citing inconsistent naming conventions and missing data on impurities, aggregates, and microbial bioburden/bacterial endotoxin levels.", "note": "A product-identity finding independent of any efficacy question. FDA states that inconsistent naming 'represent[s] a safety risk for patients as they may be dosed with a different BDS than the physician ordered' — FDA has encountered multiple salts and derivatives, including different active moieties, sold under the common name 'MOTS-c'. The label on the vial may not name the molecule in the vial.", "source": { "url": "https://www.fda.gov/media/193347/download", "title": "MOTS-c-Related Bulk Drug Substances — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, July 23-24, 2026", "publisher": "FDA", "date": "2026-07-23" }, "verifiedAt": "2026-07-16" }, { "finding": "FDA identified no in-vivo pharmacokinetic studies and no toxicology studies of MOTS-c of any kind — no acute toxicity, no repeat-dose toxicity, no genotoxicity, no developmental and reproductive toxicity, and no carcinogenicity studies.", "note": "The quoted sentence is one of five. FDA repeats the identical construction verbatim for repeat-dose toxicity, genotoxicity, developmental and reproductive toxicity, and carcinogenicity, and separately for in-vivo pharmacokinetic/toxicokinetic studies. Its summary: 'the nominator did not submit, and FDA did not identify nonclinical toxicity studies to inform safety considerations for potential clinical uses of MOTS-c (free base) or MOTS-c acetate.' This is the layer BENEATH the missing human data and it is the more surprising one — the animal safety package that would normally have to exist before a first human dose does not exist either. The rodent literature FDA reviewed is PHARMACOLOGY (does it do something), not TOXICOLOGY (does it harm). Those are different study types and the second set is empty.", "source": { "url": "https://www.fda.gov/media/193347/download", "title": "MOTS-c-Related Bulk Drug Substances — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, July 23-24, 2026", "publisher": "FDA", "date": "2026-07-23", "quote": "At the time of this evaluation, the nominator did not submit, and FDA did not identify acute toxicity studies of MOTS-c (free base) or MOTS-c acetate." }, "verifiedAt": "2026-07-16" }, { "finding": "FDA identified one pharmacokinetic-related study of MOTS-c — an in-vitro experiment in human whole blood, not an administration study — in which researchers reported that MOTS-c was rapidly broken down into shorter fragments, and FDA states it remains undetermined whether giving MOTS-c to humans can produce active concentrations at all.", "note": "The most under-reported finding in the document, and a threshold question the marketing skips entirely. In Knoop et al. 2019 — a doping-control assay development paper, not a trial — researchers incubated MOTS-c with human whole blood at 37°C and, using high resolution mass spectrometry, identified the truncated fragments MOTS-c(2-16), (3-16), (4-16) and (5-16); the authors stated the proteolytic hydrolysis was rapid and did not require long incubation. Blood in a tube is not a person, and the study administered nothing to anyone. But the implication FDA draws is the one that matters: before asking whether MOTS-c works in humans, it is not established that injected MOTS-c survives in humans long enough to do anything.", "source": { "url": "https://www.fda.gov/media/193347/download", "title": "MOTS-c-Related Bulk Drug Substances — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, July 23-24, 2026", "publisher": "FDA", "date": "2026-07-23", "quote": "It remains to be determined whether exogenous administration of MOTS-c to humans can generate pharmacologically active concentrations of the peptide over time." }, "verifiedAt": "2026-07-16" }, { "finding": "No outsourcing facility reported compounding any drug product containing MOTS-c (free base) or MOTS-c acetate to FDA between January 2017 and December 2025, and FDA states the earliest and extent of the substance's use in compounding is unknown.", "note": "Read this the way FDA scoped it, not more broadly. It covers 503B outsourcing facilities, which must report what they compounded; 503A compounders have no equivalent reporting duty, so the absence is not proof that nothing was compounded anywhere. It is evidence that the regulated, reporting tier of the compounding industry did not touch this substance for nine years. FDA separately found MOTS-c marketed online, including a holistic clinic stating it works with compounding pharmacies to obtain it and a wellness clinic promoting an IV 'cocktail' containing it — which is where the supply actually sits.", "source": { "url": "https://www.fda.gov/media/193347/download", "title": "MOTS-c-Related Bulk Drug Substances — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, July 23-24, 2026", "publisher": "FDA", "date": "2026-07-23" }, "verifiedAt": "2026-07-16" }, { "finding": "FDA states the molecular target through which MOTS-c acts remains unknown, and that it is therefore difficult to predict which organs might be affected by it.", "note": "A mechanism finding that cuts against the confident mechanistic diagrams this compound is sold with. FDA accepts that AMPK signalling is involved — in Lee et al. 2015 the metabolic effects in high-fat-diet mice were not observed when the animals also received compound C, an AMPK inhibitor — but 'involved in' is not 'the target'. FDA adds that the rodent studies did not assess dose-response relationships, which is the other half of why it calls the clinical relevance of the nonclinical work unknown.", "source": { "url": "https://www.fda.gov/media/193347/download", "title": "MOTS-c-Related Bulk Drug Substances — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, July 23-24, 2026", "publisher": "FDA", "date": "2026-07-23", "quote": "In addition, while AMPK-dependent signaling appears to contribute to the pharmacological effects of MOTS-c, the molecular targets underlying the pharmacological effects of MOTS-c remain unknown making it difficult to predict which organs are likely to be affected by MOTS-c." }, "verifiedAt": "2026-07-16" } ], "safetySignals": [ { "signal": "FAERS searches for MOTS-c adverse events through 2024-02-28, and again from 2024-02-26 through 2025-03-09, retrieved no reports.", "note": "An empty FAERS search is NOT a safety finding, and reading it as one inverts it. FDA attaches its own caveat: compounders under 503A generally do not report adverse events to FDA, and 'Unless an adverse event report is submitted to FDA, the Agency may not be aware of adverse events associated with a product compounded under section 503A.' Zero reports on a substance with zero human studies and a grey-market supply chain measures surveillance coverage, not safety.", "source": { "url": "https://www.fda.gov/media/193347/download", "title": "MOTS-c-Related Bulk Drug Substances — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, July 23-24, 2026", "publisher": "FDA", "date": "2026-07-23" }, "verifiedAt": "2026-07-16" }, { "signal": "FDA cannot rule out immunogenicity risk, citing the potential for peptide aggregation and peptide-related impurities, and notes that subcutaneous administration is generally associated with increased immunogenicity compared with intravenous.", "note": "FDA identified no clinical studies assessing immunogenicity or aggregation of MOTS-c. Its stated concern is that consequences of an immune response 'may range from antibody responses with no apparent clinical manifestations to life-threatening and catastrophic reactions', and that neutralizing antibodies could neutralise the activity of the ENDOGENOUS peptide counterpart — a risk specific to peptides the body already makes.", "source": { "url": "https://www.fda.gov/media/193347/download", "title": "MOTS-c-Related Bulk Drug Substances — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, July 23-24, 2026", "publisher": "FDA", "date": "2026-07-23", "quote": "Based on available information, there are insufficient data to conclude that MOTS-c-related BDSs do not present these risks." }, "verifiedAt": "2026-07-16" }, { "signal": "MOTS-c is listed as a prohibited substance in the Global DRO Database, which draws on the 2024 World Anti-Doping Agency Prohibited List of Hormone and Metabolic Modulators.", "note": "Recorded as FDA recorded it. Prohibition by an anti-doping body is a sport-eligibility fact, not a finding of efficacy — a substance can be banned and still have no human evidence behind it, which is exactly the case here.", "source": { "url": "https://www.fda.gov/media/193347/download", "title": "MOTS-c-Related Bulk Drug Substances — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, July 23-24, 2026", "publisher": "FDA", "date": "2026-07-23" }, "verifiedAt": "2026-07-16" } ], "faqs": [ { "question": "Is MOTS-c legal in 2026?", "answer": "MOTS-c is not on FDA's 503A bulk drug substances list — the list of substances that may lawfully be used in pharmacy compounding — as of the list revised 14 May 2026, and it does not appear in any of that list's three categories. Being absent from the list is not a licence: it means MOTS-c has not been found appropriate for compounding, not that it has been cleared for it.", "source": { "url": "https://www.fda.gov/media/94155/download", "title": "Bulk Drug Substances Nominated for Use in Compounding Under Section 503A of the Federal Food, Drug, and Cosmetic Act", "publisher": "FDA", "date": "2026-05-14" }, "verifiedAt": "2026-07-16" }, { "question": "Did MOTS-c become legal again when the nomination was withdrawn?", "answer": "No. The MOTS-c nomination was withdrawn by its nominator, Wells Pharmacy Network, and a withdrawal moves a substance sideways rather than toward legality: MOTS-c did not enter Category 1, did not join FDA's 503A bulk drug substances list, and remains outside the set of substances that may lawfully be used in compounding. FDA is in fact still evaluating both MOTS-c (free base) and MOTS-c acetate on its own initiative despite the withdrawal, and its staff have proposed not adding either substance to the list.", "source": { "url": "https://www.fda.gov/media/193347/download", "title": "MOTS-c-Related Bulk Drug Substances — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, July 23-24, 2026", "publisher": "FDA", "date": "2026-07-23", "quote": "The nomination was withdrawn, but because FDA is evaluating MOTS-c (free base) and MOTS-c acetate on its own initiative, FDA considered information submitted in this nomination as part of this evaluation." }, "verifiedAt": "2026-07-16" }, { "question": "Is there any human evidence that MOTS-c works?", "answer": "No. FDA conducted its own search of the published medical literature and stated it did not identify clinical studies evaluating administration of MOTS-c-related bulk drug substances in human subjects, by any route. The studies in which MOTS-c was actually administered were, in FDA's characterisation, limited to in-vitro and in-vivo rodent models. FDA's conclusion is that there is a lack of evidence to evaluate the effectiveness of the MOTS-c-related bulk drug substances for the nominated uses.", "source": { "url": "https://www.fda.gov/media/193347/download", "title": "MOTS-c-Related Bulk Drug Substances — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, July 23-24, 2026", "publisher": "FDA", "date": "2026-07-23", "quote": "We performed our own search of published medical literature and did not identify clinical studies evaluating administration of MOTS-c-related BDSs in human subjects." }, "verifiedAt": "2026-07-16" }, { "question": "Is MOTS-c safe?", "answer": "Nobody knows, and FDA says so directly: 'The nomination did not include, and FDA has not identified, any clinical studies or human exposure data for MOTS-c via any route of administration. Therefore, potential safety risks associated with the use of MOTS-c-related BDSs in humans are unknown.' The animal safety package is empty too — FDA identified no acute toxicity, repeat-dose toxicity, genotoxicity, reproductive toxicity or carcinogenicity studies of MOTS-c. FDA also states it cannot rule out immunogenicity risk from peptide aggregation and impurities. 'Unknown' is neither a clean bill of health nor a finding of harm: it means nobody has looked.", "source": { "url": "https://www.fda.gov/media/193347/download", "title": "MOTS-c-Related Bulk Drug Substances — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, July 23-24, 2026", "publisher": "FDA", "date": "2026-07-23", "quote": "Therefore, potential safety risks associated with the use of MOTS-c-related BDSs in humans are unknown." }, "verifiedAt": "2026-07-16" }, { "question": "Can I get MOTS-c from a compounding pharmacy?", "answer": "MOTS-c is not on FDA's 503A bulk drug substances list, so it is not a substance that may lawfully be used in pharmacy compounding, and FDA staff have proposed not adding it. Outsourcing facilities — the registered 503B tier of compounders, which must report what they make — reported compounding no drug product containing MOTS-c (free base) or MOTS-c acetate to FDA between January 2017 and December 2025. FDA nonetheless found MOTS-c marketed online for injection, including by clinics stating they obtain it through compounding pharmacies, which is where the actual supply sits.", "source": { "url": "https://www.fda.gov/media/193347/download", "title": "MOTS-c-Related Bulk Drug Substances — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, July 23-24, 2026", "publisher": "FDA", "date": "2026-07-23" }, "verifiedAt": "2026-07-16" }, { "question": "What did FDA propose at the July 2026 PCAC meeting about MOTS-c?", "answer": "FDA staff proposed not adding MOTS-c (free base) or MOTS-c acetate to the 503A bulk drug substances list. The proposal appears in FDA's evaluation memorandum, internally dated 5/11/2026, inside the briefing package prepared for the Pharmacy Compounding Advisory Committee meeting of 23-24 July 2026. FDA gave four grounds: that neither substance is well-characterized physically and chemically, that their use in compounding is unknown, that no nonclinical data exist to inform safety for potential clinical uses, and that there are no clinical studies assessing safety or effectiveness in humans. A staff proposal is not a final determination — FDA states it will not issue one until the advisory committee process has been considered and all reviews finalized.", "source": { "url": "https://www.fda.gov/media/193347/download", "title": "MOTS-c-Related Bulk Drug Substances — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, July 23-24, 2026", "publisher": "FDA", "date": "2026-07-23", "quote": "Accordingly, we propose not adding MOTS-c (free base) or MOTS-c acetate to the 503A Bulks List." }, "verifiedAt": "2026-07-16" } ] }, { "slug": "octreotide", "name": "Octreotide", "aliases": [ "Sandostatin", "Sandostatin LAR Depot", "Mycapssa", "Bynfezia Pen", "octreotide acetate" ], "url": "https://peptides101.com/compounds/octreotide", "moleculeNote": "A synthetic somatostatin analogue. The Sandostatin Injection label describes octreotide as 'a cyclic octapeptide' and 'a long-acting octapeptide with pharmacologic actions mimicking those of the natural hormone somatostatin', giving its molecular weight as 1019.3 g/mol for the free peptide, C49H66N10O10S2. Every FDA-approved octreotide product contains the ACETATE SALT. The disambiguation that matters here is not sequence — all four applications are the same molecule — it is PRODUCT. Sandostatin Injection is a subcutaneous or intravenous solution; Sandostatin LAR Depot is a long-acting injectable suspension; Mycapssa is a delayed-release oral capsule; Bynfezia Pen is a subcutaneous solution in a pen. Their labels are not interchangeable, and two of them are approved only as maintenance in patients who have already responded to something else. 'Octreotide' does not identify a product.", "quickAnswer": "Octreotide is an FDA-approved synthetic somatostatin analogue, approved under four new drug applications — Sandostatin Injection (NDA 019667), Sandostatin LAR Depot (NDA 021008), Mycapssa delayed-release oral capsules (NDA 208232) and Bynfezia Pen (NDA 213224) — plus thirteen generic octreotide acetate ANDAs listed in Drugs@FDA. The approved indications are narrow and product-specific: acromegaly after inadequate response to surgery, pituitary irradiation and bromocriptine; severe diarrhea and flushing episodes associated with metastatic carcinoid tumors; and profuse watery diarrhea associated with VIPomas — with Sandostatin LAR Depot and Mycapssa approved only as maintenance in patients who already responded to another somatostatin analogue. The Sandostatin Injection label states its own limitation verbatim: 'Improvement in clinical signs and symptoms, or reduction in tumor size or rate of growth, were not shown in clinical trials performed with Sandostatin Injection; these trials were not optimally designed to detect such effects.' The same label reports a 63% incidence of biliary tract abnormalities in clinical trials. Octreotide appears in none of Categories 1, 2 or 3 of FDA's 503A bulk drug substances list updated 2026-05-14.", "fdaStatus": { "value": "approved", "note": "FDA-approved, and unusually well-populated: Drugs@FDA returns four NDAs and thirteen ANDAs for octreotide. Verified 2026-08-02 by querying openFDA `drug/drugsfda` on `openfda.generic_name:\"octreotide\"` (17 applications) and cross-checking `products.active_ingredients.name`. The four NDAs, with the original approval action Drugs@FDA records for each: NDA 019667 SANDOSTATIN, Novartis, 1988-10-21, priority review, Type 1 New Molecular Entity; NDA 021008 SANDOSTATIN LAR DEPOT, Novartis, 1998-11-25; NDA 208232 MYCAPSSA, Chiesi, 2020-06-26; NDA 213224 BYNFEZIA PEN, Sun Pharmaceutical, 2024-09-27 (read the fdaFindings entry on this one — the date is not the whole story). Marketing status is per-product, not per-molecule: two Sandostatin Injection strengths are listed Discontinued, each carrying the Drugs@FDA annotation 'Federal Register determination that product was not discontinued or withdrawn for safety or effectiveness reasons', while three remain Prescription. The franchise is marketed. Approval is always for a specific indication and population — read the approval record below, and read the Limitations of Use under fdaFindings, which are in the label itself.", "source": { "url": "https://www.accessdata.fda.gov/spl/data/4e2c9856-1836-49f0-9472-4dbeeb408f39/4e2c9856-1836-49f0-9472-4dbeeb408f39.xml", "title": "SANDOSTATIN (octreotide acetate) injection — Prescribing Information (SPL)", "publisher": "FDA", "date": "2026-07-22", "quote": "Sandostatin Injection is a somatostatin analogue indicated: Acromegaly: To reduce blood levels of growth hormone (GH) and insulin growth factor-1 (IGF-1; somatomedin C) in acromegaly patients who have had inadequate response to or cannot be treated with surgical resection, pituitary irradiation, and bromocriptine mesylate at maximally tolerated doses." }, "verifiedAt": "2026-08-02" }, "compoundingStatus": null, "evidence": { "tier": "proven-in-humans", "humanAdministrationChecked": true, "note": "Administration check RUN, not assumed. OPTIMAL (NCT03252353) was opened and read on 2026-08-02: intervention type DRUG, octreotide capsules administered orally versus matching placebo capsules, Phase 3, randomised, parallel-assignment, triple-masked (participant, care provider, investigator), enrolment 56 ACTUAL, lead sponsor Chiasma, Inc., primary completion 2019-06-13 ACTUAL, hasResults true. Octreotide was ADMINISTERED to humans — it was not measured as an endogenous biomarker, which is the trap that reduces MOTS-c and TB-500 from an apparent five human RCTs to an actual zero. The trial is described independently in section 14 of the FDA-approved MYCAPSSA label, which reports that in this 9-month randomised, double-blind, placebo-controlled study of 56 patients with acromegaly, 58% of patients treated with MYCAPSSA versus 19% of patients treated with placebo maintained the biochemical response defined as IGF-1 at or below the upper limit of normal at the end of treatment, and that 25% of patients treated with MYCAPSSA required discontinuation and treatment with other somatostatin analogs at some point during the study. The SANDOSTATIN LAR DEPOT label additionally describes three acromegaly trials — two enrolling 101 patients in total and a third 12-month study enrolling 151 — and a 6-month trial in 93 patients with malignant carcinoid syndrome. Those trials also administered the drug. SCOPE, and it is narrow. This tier attaches to the approved products and the approved endpoints, which are biochemical and symptomatic. It does NOT extend to tumour outcomes: the Sandostatin Injection label states that improvement in clinical signs and symptoms, or reduction in tumor size or rate of growth, were not shown in its clinical trials, and the LAR label states the effect on tumor size, rate of growth and development of metastases has not been determined in carcinoid syndrome and VIPomas. Both statements are recorded verbatim under fdaFindings. A tier label is coarse; this is where it is true.", "source": { "url": "https://clinicaltrials.gov/study/NCT03252353", "title": "OPTIMAL — Efficacy and Safety of Octreotide Capsules (MYCAPSSA) in Acromegaly", "publisher": "ClinicalTrials.gov", "date": "2019-06-13" }, "verifiedAt": "2026-08-02" }, "fdaApproval": { "applicationNumber": "NDA 019667 (Sandostatin Injection); NDA 021008 (Sandostatin LAR Depot); NDA 208232 (Mycapssa delayed-release capsules); NDA 213224 (Bynfezia Pen)", "brandName": "Sandostatin, Sandostatin LAR Depot, Mycapssa, Bynfezia Pen", "approvedIndication": "SANDOSTATIN INJECTION (NDA 019667) — 1.1 Acromegaly: Sandostatin Injection is indicated to reduce blood levels of growth hormone (GH) and insulin growth factor-1 (IGF-1; somatomedin C) in acromegaly patients who have had inadequate response to or cannot be treated with surgical resection, pituitary irradiation, and bromocriptine mesylate at maximally tolerated doses. 1.2 Carcinoid Tumors: Sandostatin Injection is indicated for treatment of severe diarrhea and flushing episodes associated with metastatic carcinoid tumors. 1.3 Vasoactive Intestinal Peptide Tumors: Sandostatin Injection is indicated for the treatment of the profuse watery diarrhea associated with vasoactive intestinal peptide tumors (VIPomas)-secreting tumors. 1.4 Important Limitations of Use: Improvement in clinical signs and symptoms, or reduction in tumor size or rate of growth, were not shown in clinical trials performed with Sandostatin Injection; these trials were not optimally designed to detect such effects. — SANDOSTATIN LAR DEPOT (NDA 021008): SANDOSTATIN LAR DEPOT 10 mg, 20 mg, and 30 mg is indicated in patients in whom initial treatment with Sandostatin Injection has been shown to be effective and tolerated. 1.1 Acromegaly: Long-term maintenance therapy in acromegalic patients who have had an inadequate response to surgery and/or radiotherapy, or for whom surgery and/or radiotherapy, is not an option. 1.2 Carcinoid Tumors: Long-term treatment of the severe diarrhea and flushing episodes associated with metastatic carcinoid tumors. 1.3 Vasoactive Intestinal Peptide Tumors (VIPomas): Long-term treatment of the profuse watery diarrhea associated with VIP-secreting tumors. — MYCAPSSA (NDA 208232): MYCAPSSA is indicated for long-term maintenance treatment in acromegaly patients who have responded to and tolerated treatment with octreotide or lanreotide. — BYNFEZIA PEN (NDA 213224): BYNFEZIA PEN is a somatostatin analogue indicated: Acromegaly: To reduce blood levels of growth hormone (GH) and insulin growth factor 1 (IGF-1; somatomedin C) in acromegaly patients who have had inadequate response to or cannot be treated with surgical resection, pituitary irradiation, and bromocriptine mesylate at maximally tolerated doses. Carcinoid Tumors: For the symptomatic treatment of patients with metastatic carcinoid tumors where it suppresses or inhibits the severe diarrhea and flushing episodes associated with the disease. Vasoactive Intestinal Peptide Tumors (VIPomas): For the treatment of profuse watery diarrhea associated with VIP-secreting tumors.", "discontinued": false, "source": { "url": "https://www.accessdata.fda.gov/spl/data/4e2c9856-1836-49f0-9472-4dbeeb408f39/4e2c9856-1836-49f0-9472-4dbeeb408f39.xml", "title": "SANDOSTATIN (octreotide acetate) injection — Prescribing Information (SPL)", "publisher": "FDA", "date": "2026-07-22" }, "verifiedAt": "2026-08-02" }, "fdaFindings": [ { "finding": "The FDA-approved labeling for Sandostatin Injection carries an Important Limitations of Use section stating that improvement in clinical signs and symptoms, or reduction in tumor size or rate of growth, were not shown in clinical trials performed with Sandostatin Injection, and that these trials were not optimally designed to detect such effects.", "note": "The most useful sentence on this record, and it is in an approved label rather than an enforcement document. Read it precisely, because it can be over-read in both directions. It is NOT a statement that the drug does not work — the approved indications stand, and the label's own clinical studies describe hormonal and symptomatic control. It IS a statement that a specific class of benefit was not demonstrated, together with FDA's reason: the trials were not designed to detect it. Absence of a finding is not a negative finding, and the label says which one this is. This is the same distinction the site draws when FDA declines to reach a question — the difference between 'we looked and it was not there' and 'we did not look'.", "source": { "url": "https://www.accessdata.fda.gov/spl/data/4e2c9856-1836-49f0-9472-4dbeeb408f39/4e2c9856-1836-49f0-9472-4dbeeb408f39.xml", "title": "SANDOSTATIN (octreotide acetate) injection — Prescribing Information (SPL)", "publisher": "FDA", "date": "2026-07-22", "quote": "Improvement in clinical signs and symptoms, or reduction in tumor size or rate of growth, were not shown in clinical trials performed with Sandostatin Injection; these trials were not optimally designed to detect such effects." }, "verifiedAt": "2026-08-02" }, { "finding": "The FDA-approved labeling for Sandostatin LAR Depot states that in patients with carcinoid syndrome and VIPomas, the effect of Sandostatin Injection and Sandostatin LAR Depot on tumor size, rate of growth and development of metastases has not been determined.", "note": "The second label saying the same thing about the same gap, which is why it is recorded separately rather than folded into a note on the first. A claim about two labels needs two labels. Note the scope difference: this one is confined to carcinoid syndrome and VIPomas, and it names three distinct undetermined endpoints — size, growth rate and development of metastases. Section 14 of the same label separately reports median reductions in tumour volume in two open-label studies in previously untreated acromegalic patients, which is a different disease, a different endpoint and an uncontrolled design. Those two facts are not in conflict; conflating them would be the error.", "source": { "url": "https://www.accessdata.fda.gov/spl/data/d0b7fe9e-7000-4b79-ba3b-291ce92c14f9/d0b7fe9e-7000-4b79-ba3b-291ce92c14f9.xml", "title": "SANDOSTATIN LAR DEPOT (octreotide acetate) for injectable suspension — Prescribing Information (SPL)", "publisher": "FDA", "date": "2025-12-22", "quote": "In patients with carcinoid syndrome and VIPomas, the effect of Sandostatin Injection and SANDOSTATIN LAR DEPOT on tumor size, rate of growth and development of metastases, has not been determined." }, "verifiedAt": "2026-08-02" }, { "finding": "Sandostatin LAR Depot is not approved as an initial treatment. Its FDA-approved labeling indicates it in patients in whom initial treatment with Sandostatin Injection has been shown to be effective and tolerated.", "note": "Recorded because product-level gating is invisible if you only know the molecule. Both of the convenience formulations are downstream products by label design — this one requires prior response to the subcutaneous injection, and Mycapssa requires prior response to octreotide or lanreotide. The label's clinical trials match that design: they were performed in patients who had already been receiving Sandostatin Injection.", "source": { "url": "https://www.accessdata.fda.gov/spl/data/d0b7fe9e-7000-4b79-ba3b-291ce92c14f9/d0b7fe9e-7000-4b79-ba3b-291ce92c14f9.xml", "title": "SANDOSTATIN LAR DEPOT (octreotide acetate) for injectable suspension — Prescribing Information (SPL)", "publisher": "FDA", "date": "2025-12-22", "quote": "SANDOSTATIN LAR DEPOT 10 mg, 20 mg, and 30 mg is indicated in patients in whom initial treatment with Sandostatin Injection has been shown to be effective and tolerated." }, "verifiedAt": "2026-08-02" }, { "finding": "Mycapssa, the oral delayed-release octreotide capsule, is approved only for long-term maintenance treatment in acromegaly patients who have responded to and tolerated treatment with octreotide or lanreotide. Its labeling carries no carcinoid or VIPoma indication.", "note": "The narrowest approval of the four, and the one most likely to be over-read as 'oral octreotide is approved'. It is approved for one disease, in one population, defined by prior response to an injectable somatostatin analogue. The injectable products carry three indications; this one carries a fragment of the first. Same molecule, materially different label.", "source": { "url": "https://www.accessdata.fda.gov/spl/data/58d80bc6-bdfb-4908-93e7-aace447c8d1a/58d80bc6-bdfb-4908-93e7-aace447c8d1a.xml", "title": "MYCAPSSA (octreotide) delayed-release capsules, for oral use — Prescribing Information (SPL)", "publisher": "FDA", "date": "2025-07-24", "quote": "MYCAPSSA is indicated for long-term maintenance treatment in acromegaly patients who have responded to and tolerated treatment with octreotide or lanreotide." }, "verifiedAt": "2026-08-02" }, { "finding": "Octreotide appears in none of Categories 1, 2 or 3 of FDA's list of bulk drug substances nominated for use in compounding under section 503A, updated 2026-05-14.", "note": "Recorded to close a misreading, not to assert a status — which is why this record has no `compoundingStatus` field at all. Verified by downloading the document with a browser user-agent and text-extracting it locally on 2026-08-02: 'octreotide' returns 0 hits and 'somatostatin' returns 0 hits. This absence means something entirely different from BPC-157's absence. BPC-157 was nominated and left Category 2 when the nominators withdrew. Octreotide was never in this system: a 503A bulks nomination is a route for substances WITHOUT an approved product, and octreotide has seventeen approved applications. Categorical silence here is neither permission nor a safety finding, and it says nothing at all about what a pharmacy may lawfully do with an approved octreotide drug product. SCOPE LIMIT: this record makes no claim about the separate 503B bulks list. That document was not read for this compound, and a blank is honest.", "source": { "url": "https://www.fda.gov/media/94155/download", "title": "Bulk Drug Substances Nominated for Use in Compounding Under Section 503A of the Federal Food, Drug, and Cosmetic Act", "publisher": "FDA", "date": "2026-05-14" }, "verifiedAt": "2026-08-02" }, { "finding": "FDA's approval letter for Bynfezia Pen (NDA 213224), filed in the 2024 approval-letter directory, acknowledges receipt of an amendment dated March 29, 2024 that constituted a complete response to FDA's May 19, 2021 action letter, and approves the application for the acromegaly, carcinoid tumor and VIPoma indications.", "note": "A deliberate wrinkle, recorded rather than smoothed over. Drugs@FDA lists the ORIG approval action for NDA 213224 as 2024-09-27 with submission class 'Type 5 - New Formulation or New Manufacturer'. But accessdata.fda.gov also serves an approval letter for the same submission (213224Orig1s000ltr.pdf) under the 2020 directory, referring to the same application dated and received March 28, 2019 and to a January 28, 2020 final printed labeling submission. Both PDFs were downloaded and text-extracted on 2026-08-02. The 2024 letter's reference to a complete response to a May 19, 2021 action letter is what makes the sequence non-obvious. This record therefore does NOT state a single clean 'Bynfezia was approved in year X' — it states what each document says. Anyone needing the definitive approval history should read both letters and the Drugs@FDA submission table rather than trust a one-line date.", "source": { "url": "https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2024/213224Orig1s000ltr.pdf", "title": "NDA 213224 Approval Letter — Bynfezia Pen (octreotide acetate) injection, for subcutaneous use", "publisher": "FDA", "date": "2024-09-27", "quote": "We acknowledge receipt of your amendment dated March 29, 2024, which constituted a complete response to our May 19, 2021, action letter." }, "verifiedAt": "2026-08-02" }, { "finding": "Drugs@FDA lists seventeen applications with the generic name octreotide: four NDAs — Sandostatin (NDA 019667), Sandostatin LAR Depot (NDA 021008), Mycapssa (NDA 208232) and Bynfezia Pen (NDA 213224) — and thirteen abbreviated new drug applications for generic octreotide acetate, from sponsors including Fresenius Kabi, Meitheal, Hikma/West-Ward, Heritage, Mylan, Teva, Gland and Sun.", "note": "Recorded because the count is the answer to a question people actually ask — whether generic octreotide exists — and because it is the field-query check this library once got wrong on sermorelin. The query above searches `openfda.generic_name`; `products.active_ingredients.name` was checked as well and agrees. Marketing status varies application by application and product by product within an application; a listed ANDA is not by itself evidence that a given presentation is currently marketed.", "source": { "url": "https://api.fda.gov/drug/drugsfda.json?search=openfda.generic_name:\"octreotide\"&limit=100", "title": "Drugs@FDA — applications with generic name octreotide (openFDA drug/drugsfda)", "publisher": "FDA", "date": "2026-07-31" }, "verifiedAt": "2026-08-02" } ], "safetySignals": [ { "signal": "Cholelithiasis and complications of cholelithiasis. The Sandostatin Injection label states the drug may inhibit gallbladder contractility and decrease bile secretion, which may lead to gallbladder abnormalities or sludge, and that acute cholecystitis, ascending cholangitis, biliary obstruction, cholestatic hepatitis or pancreatitis have been reported with therapy. In clinical trials, primarily in patients with acromegaly or psoriasis, the incidence of biliary tract abnormalities was 63% — 27% gallstones, 24% sludge without stones and 12% biliary duct dilatation. One patient developed ascending cholangitis during therapy and died.", "note": "The dominant safety signal on this molecule and the one with a real denominator behind it — a trial population, not a spontaneous-report count. The label also reports that the incidence of stones or sludge in patients who received Sandostatin Injection for 12 months or longer was 52%, and that fewer than 2% of patients treated for one month or less developed gallstones, so exposure duration is doing most of the work. The same warning appears in the Sandostatin LAR Depot and Mycapssa labels, both of which note postmarketing reports of cholelithiasis resulting in complications including cholecystitis, cholangitis, pancreatitis and requiring cholecystectomy.", "source": { "url": "https://www.accessdata.fda.gov/spl/data/4e2c9856-1836-49f0-9472-4dbeeb408f39/4e2c9856-1836-49f0-9472-4dbeeb408f39.xml", "title": "SANDOSTATIN (octreotide acetate) injection — Prescribing Information (SPL)", "publisher": "FDA", "date": "2026-07-22", "quote": "In clinical trials (primarily patients with acromegaly or psoriasis), the incidence of biliary tract abnormalities was 63% (27% gallstones, 24% sludge without stones, 12% biliary duct dilatation)." }, "verifiedAt": "2026-08-02" }, { "signal": "Cardiac function abnormalities. The Sandostatin Injection label states that patients receiving the drug intravenously may be at increased risk for higher degree atrioventricular blocks, and that complete atrioventricular block was reported in postmarketing reports in patients receiving it intravenously during surgical procedures. In acromegalic patients, the label reports bradycardia developed in 25%, conduction abnormalities occurred in 10% and arrhythmias occurred in 9% during therapy.", "note": "Route-dependent, which is the part that gets lost. The label states that in the majority of the complete-AV-block reports the drug was given at higher than recommended amounts and/or as a continuous intravenous infusion, and adds that the safety of continuous intravenous infusion has not been established for the approved indications. It also records QT prolongation, axis shifts, early repolarization, low voltage, R/S transition and early R-wave progression among observed ECG changes, while noting these changes are not uncommon in acromegalic patients — a confounder the label names itself. One acromegalic patient with severe congestive heart failure worsened on initiation and improved on discontinuation, confirmed by a positive rechallenge.", "source": { "url": "https://www.accessdata.fda.gov/spl/data/4e2c9856-1836-49f0-9472-4dbeeb408f39/4e2c9856-1836-49f0-9472-4dbeeb408f39.xml", "title": "SANDOSTATIN (octreotide acetate) injection — Prescribing Information (SPL)", "publisher": "FDA", "date": "2026-07-22", "quote": "Patients who receive Sandostatin Injection intravenously may be at increased risk for higher degree atrioventricular blocks. In postmarketing reports, complete atrioventricular block was reported in patients receiving IV Sandostatin Injection during surgical procedures." }, "verifiedAt": "2026-08-02" }, { "signal": "Hyperglycemia and hypoglycemia. The Sandostatin Injection label states the drug alters the balance between the counter-regulatory hormones insulin, glucagon and growth hormone, which may result in hypoglycemia or hyperglycemia, and that this may result in overt diabetes mellitus. Hypoglycemia and hyperglycemia occurred in 3% and 16% of acromegalic patients respectively. Severe hyperglycemia, subsequent pneumonia and death following initiation of therapy was reported in one patient with no history of hyperglycemia.", "note": "Recorded with the fatality because the label records it, and because the patient had no prior history — the risk is not confined to people already known to be dysglycaemic. The Mycapssa label reports the corresponding rates from its own trials as increased blood glucose 7%, hypoglycemia 4% and diabetes mellitus 1%. Different products, different populations, different trials; the numbers are not comparable and are recorded as what each label says rather than merged.", "source": { "url": "https://www.accessdata.fda.gov/spl/data/4e2c9856-1836-49f0-9472-4dbeeb408f39/4e2c9856-1836-49f0-9472-4dbeeb408f39.xml", "title": "SANDOSTATIN (octreotide acetate) injection — Prescribing Information (SPL)", "publisher": "FDA", "date": "2026-07-22", "quote": "Severe hyperglycemia, subsequent pneumonia, and death following initiation of Sandostatin Injection therapy was reported in one patient with no history of hyperglycemia." }, "verifiedAt": "2026-08-02" }, { "signal": "Thyroid function abnormalities. The Sandostatin Injection label states that octreotide suppresses secretion of thyroid stimulating hormone, which may result in hypothyroidism, and recommends baseline and periodic assessment of thyroid function during chronic therapy. In acromegalic patients the label reports biochemical hypothyroidism alone in 12%, goiter in 8%, and 4% requiring initiation of thyroid replacement therapy.", "note": "A mechanism-level effect on a second endocrine axis, which is what a somatostatin analogue does — somatostatin inhibits more than growth hormone. The label notes that in patients without acromegaly, hypothyroidism has only been reported in several isolated patients and goiter has not been reported, so the population matters.", "source": { "url": "https://www.accessdata.fda.gov/spl/data/4e2c9856-1836-49f0-9472-4dbeeb408f39/4e2c9856-1836-49f0-9472-4dbeeb408f39.xml", "title": "SANDOSTATIN (octreotide acetate) injection — Prescribing Information (SPL)", "publisher": "FDA", "date": "2026-07-22", "quote": "Octreotide suppresses secretion of thyroid stimulating hormone (TSH), which may result in hypothyroidism." }, "verifiedAt": "2026-08-02" }, { "signal": "Steatorrhea, malabsorption of dietary fats, and changes in vitamin B12 levels. The Sandostatin Injection label states that somatostatin analogs reversibly inhibit secretion of pancreatic enzymes and bile acids, which may result in malabsorption of dietary fats and subsequent symptoms of steatorrhea, loose stools, abdominal bloating and weight loss, and directs evaluation for potential pancreatic exocrine insufficiency. It also states that depressed vitamin B12 levels and abnormal Schilling's tests have been observed in some patients receiving therapy.", "note": "Worth reading because weight loss appears here as an ADVERSE finding attributable to fat malabsorption, not as a benefit. The label frames it as a symptom to be evaluated for pancreatic exocrine insufficiency. The same warning is carried in the Sandostatin LAR Depot and Mycapssa labels, which describe it as a somatostatin-analog class effect.", "source": { "url": "https://www.accessdata.fda.gov/spl/data/4e2c9856-1836-49f0-9472-4dbeeb408f39/4e2c9856-1836-49f0-9472-4dbeeb408f39.xml", "title": "SANDOSTATIN (octreotide acetate) injection — Prescribing Information (SPL)", "publisher": "FDA", "date": "2026-07-22", "quote": "Somatostatin analogs reversibly inhibit secretion of pancreatic enzymes and bile acids, which may result in malabsorption of dietary fats and subsequent symptoms of steatorrhea, loose stools, abdominal bloating, and weight loss." }, "verifiedAt": "2026-08-02" }, { "signal": "The oral product carries the same class warnings as the injections. The Mycapssa label carries warnings and precautions for cholelithiasis and complications of cholelithiasis, hypoglycemia or hyperglycemia, thyroid function abnormalities, cardiac function abnormalities, steatorrhea and malabsorption of dietary fats, and changes in vitamin B12 levels.", "note": "Recorded on its own because the oral route invites the opposite intuition. Mycapssa is a capsule and it carries the same six warning categories as the injectable products. Route of administration is not the risk axis here. The label reports bradycardia 2%, conduction abnormalities 1% and arrhythmias/tachycardia 2% in its own trials, and notes these ECG changes may occur in patients with acromegaly independently.", "source": { "url": "https://www.accessdata.fda.gov/spl/data/58d80bc6-bdfb-4908-93e7-aace447c8d1a/58d80bc6-bdfb-4908-93e7-aace447c8d1a.xml", "title": "MYCAPSSA (octreotide) delayed-release capsules, for oral use — Prescribing Information (SPL)", "publisher": "FDA", "date": "2025-07-24", "quote": "MYCAPSSA may inhibit gallbladder contractility and decrease bile secretion, which may lead to gallbladder abnormalities or sludge." }, "verifiedAt": "2026-08-02" }, { "signal": "No FDA-approved octreotide product reviewed for this record carries a boxed warning. The Structured Product Labeling for Sandostatin Injection, Sandostatin LAR Depot, Mycapssa and Bynfezia Pen contains no boxed warning section.", "note": "Recorded as an explicit negative so that the absence is a checked fact rather than an oversight. Verified 2026-08-02 by querying the `boxed_warning` field of the openFDA `drug/label` records for all four NDAs: empty in every one. The absence of a boxed warning is not a safety endorsement — the six warnings above are in the same labels — and it is recorded here only because a reader comparing this record with the GLP-1 records will notice the difference and should know it was looked at.", "source": { "url": "https://www.accessdata.fda.gov/spl/data/4e2c9856-1836-49f0-9472-4dbeeb408f39/4e2c9856-1836-49f0-9472-4dbeeb408f39.xml", "title": "SANDOSTATIN (octreotide acetate) injection — Prescribing Information (SPL)", "publisher": "FDA", "date": "2026-07-22" }, "verifiedAt": "2026-08-02" } ], "faqs": [ { "question": "Is octreotide FDA-approved?", "answer": "Yes. Octreotide is approved under four FDA new drug applications — Sandostatin Injection (NDA 019667), Sandostatin LAR Depot (NDA 021008), Mycapssa delayed-release oral capsules (NDA 208232) and Bynfezia Pen (NDA 213224) — and Drugs@FDA additionally lists thirteen abbreviated new drug applications for generic octreotide acetate, from sponsors including Fresenius Kabi, Meitheal, Hikma/West-Ward, Heritage, Mylan, Teva, Gland and Sun. Drugs@FDA records the original approval action for NDA 019667 as 21 October 1988, under priority review, classified Type 1 — New Molecular Entity. Approval is per application and per product, not per molecule: marketing status varies across the seventeen applications, and two Sandostatin Injection strengths are individually listed as Discontinued, each carrying the Drugs@FDA annotation that the product was not discontinued or withdrawn for safety or effectiveness reasons.", "source": { "url": "https://api.fda.gov/drug/drugsfda.json?search=openfda.generic_name:\"octreotide\"&limit=100", "title": "Drugs@FDA — applications with generic name octreotide (openFDA drug/drugsfda)", "publisher": "FDA", "date": "2026-07-31" }, "verifiedAt": "2026-08-02" }, { "question": "What is octreotide approved to treat?", "answer": "Three things, and they are narrower than the molecule's reputation. The FDA-approved labeling for Sandostatin Injection indicates it to reduce blood levels of growth hormone and IGF-1 'in acromegaly patients who have had inadequate response to or cannot be treated with surgical resection, pituitary irradiation, and bromocriptine mesylate at maximally tolerated doses'; for treatment of severe diarrhea and flushing episodes associated with metastatic carcinoid tumors; and for treatment of the profuse watery diarrhea associated with vasoactive intestinal peptide tumors (VIPomas). Read the gating: the acromegaly indication is written as a second-line one. Anything outside these three indications is off-label use, which is a decision for a licensed prescriber and is not something this label supports.", "source": { "url": "https://www.accessdata.fda.gov/spl/data/4e2c9856-1836-49f0-9472-4dbeeb408f39/4e2c9856-1836-49f0-9472-4dbeeb408f39.xml", "title": "SANDOSTATIN (octreotide acetate) injection — Prescribing Information (SPL)", "publisher": "FDA", "date": "2026-07-22", "quote": "Sandostatin Injection is indicated for treatment of severe diarrhea and flushing episodes associated with metastatic carcinoid tumors." }, "verifiedAt": "2026-08-02" }, { "question": "Does octreotide shrink tumors?", "answer": "The FDA-approved labeling does not claim it does, and says so explicitly. Sandostatin Injection's label carries an Important Limitations of Use section reading: 'Improvement in clinical signs and symptoms, or reduction in tumor size or rate of growth, were not shown in clinical trials performed with Sandostatin Injection; these trials were not optimally designed to detect such effects.' The Sandostatin LAR Depot label states separately that in patients with carcinoid syndrome and VIPomas, the effect on tumor size, rate of growth and development of metastases has not been determined. Read the reason FDA gives, because it changes the meaning: these are statements that the question was not adequately studied, not findings that the drug failed. Absence of a finding is not a negative finding. Separately, section 14 of the LAR label reports median reductions in tumour volume in two open-label studies in previously untreated acromegalic patients — a different disease and an uncontrolled design, which is why the Limitations of Use paragraph still stands.", "source": { "url": "https://www.accessdata.fda.gov/spl/data/4e2c9856-1836-49f0-9472-4dbeeb408f39/4e2c9856-1836-49f0-9472-4dbeeb408f39.xml", "title": "SANDOSTATIN (octreotide acetate) injection — Prescribing Information (SPL)", "publisher": "FDA", "date": "2026-07-22", "quote": "Improvement in clinical signs and symptoms, or reduction in tumor size or rate of growth, were not shown in clinical trials performed with Sandostatin Injection; these trials were not optimally designed to detect such effects." }, "verifiedAt": "2026-08-02" }, { "question": "Is there an oral form of octreotide?", "answer": "Yes — Mycapssa (NDA 208232) is an FDA-approved delayed-release octreotide capsule for oral use, but its approval is much narrower than the injections'. Its labeling indicates it 'for long-term maintenance treatment in acromegaly patients who have responded to and tolerated treatment with octreotide or lanreotide'. It carries no carcinoid indication and no VIPoma indication, and by the terms of the indication it is not a starting treatment — the label describes patients who have already responded to an injectable somatostatin analogue. Its efficacy was established in a 9-month randomised, double-blind, placebo-controlled study of 56 patients with acromegaly (NCT03252353), in which 58% of patients treated with Mycapssa versus 19% of patients treated with placebo maintained the biochemical response defined as IGF-1 at or below the upper limit of normal; 25% of patients treated with Mycapssa required discontinuation and treatment with another somatostatin analog at some point during the study.", "source": { "url": "https://www.accessdata.fda.gov/spl/data/58d80bc6-bdfb-4908-93e7-aace447c8d1a/58d80bc6-bdfb-4908-93e7-aace447c8d1a.xml", "title": "MYCAPSSA (octreotide) delayed-release capsules, for oral use — Prescribing Information (SPL)", "publisher": "FDA", "date": "2025-07-24", "quote": "MYCAPSSA is indicated for long-term maintenance treatment in acromegaly patients who have responded to and tolerated treatment with octreotide or lanreotide." }, "verifiedAt": "2026-08-02" }, { "question": "What are the main risks of octreotide?", "answer": "The FDA-approved labeling's leading concern is the gallbladder. The Sandostatin Injection label states the drug may inhibit gallbladder contractility and decrease bile secretion, which may lead to gallbladder abnormalities or sludge, and reports that in clinical trials — primarily in patients with acromegaly or psoriasis — 'the incidence of biliary tract abnormalities was 63% (27% gallstones, 24% sludge without stones, 12% biliary duct dilatation)', rising to 52% for stones or sludge among patients treated for 12 months or longer. The label also records that one patient developed ascending cholangitis during therapy and died. Beyond the gallbladder, the same label carries warnings for cardiac function abnormalities including complete atrioventricular block reported with intravenous administration during surgical procedures, hyperglycemia and hypoglycemia, thyroid function abnormalities from suppression of thyroid stimulating hormone, steatorrhea and malabsorption of dietary fats, and depressed vitamin B12 levels. No FDA-approved octreotide product reviewed here carries a boxed warning.", "source": { "url": "https://www.accessdata.fda.gov/spl/data/4e2c9856-1836-49f0-9472-4dbeeb408f39/4e2c9856-1836-49f0-9472-4dbeeb408f39.xml", "title": "SANDOSTATIN (octreotide acetate) injection — Prescribing Information (SPL)", "publisher": "FDA", "date": "2026-07-22", "quote": "In clinical trials (primarily patients with acromegaly or psoriasis), the incidence of biliary tract abnormalities was 63% (27% gallstones, 24% sludge without stones, 12% biliary duct dilatation)." }, "verifiedAt": "2026-08-02" }, { "question": "Is octreotide on FDA's 503A compounding list?", "answer": "No. Octreotide appears in none of Categories 1, 2 or 3 of FDA's list of bulk drug substances nominated for use in compounding under section 503A, updated 14 May 2026 — the document was downloaded and text-extracted on 2 August 2026 and returns zero hits for both 'octreotide' and 'somatostatin'. Read what that absence does and does not mean. It is not a safety finding and it is not permission. It also means something different from BPC-157's absence from the same list: BPC-157 was nominated and left Category 2 when the nominators withdrew, whereas a 503A bulks nomination is a route for substances without an approved drug product, and octreotide has seventeen approved applications in Drugs@FDA. That is why this record carries no 503A compounding status at all rather than recording octreotide as 'never nominated' — the list can establish absence, not the reason for it.", "source": { "url": "https://www.fda.gov/media/94155/download", "title": "Bulk Drug Substances Nominated for Use in Compounding Under Section 503A of the Federal Food, Drug, and Cosmetic Act", "publisher": "FDA", "date": "2026-05-14" }, "verifiedAt": "2026-08-02" } ] }, { "slug": "oxytocin", "name": "Oxytocin", "aliases": [ "Pitocin", "Syntocinon", "oxytocin injection USP", "OT", "the love hormone", "the bonding hormone" ], "url": "https://peptides101.com/compounds/oxytocin", "moleculeNote": "A nonapeptide. The FDA-approved labeling describes Pitocin as 'a sterile, clear, colorless aqueous solution of synthetic oxytocin, for intravenous infusion or intramuscular injection', prepared synthetically 'to avoid possible contamination with vasopressin (ADH) and other small polypeptides with biologic activity'. The disambiguation that matters here is not sequence — it is ROUTE AND PRODUCT. Every oxytocin product FDA currently approves is an injection. Oxytocin sold as a nasal spray, a sublingual troche, an oral drop or a 'research' vial is not one of those products, and the approval, the labeling and the labeled warnings recorded below describe the injections and nothing else. One pharmacology note the label itself flags, because it explains a real risk rather than decorating the entry: oxytocin 'even in its pure form has inherent pressor and antidiuretic properties which may become manifest when large doses are administered', which the label attributes to the fact 'that oxytocin and vasopressin differ in regard to only two of the eight amino acids'. The antidiuretic effect is the mechanism behind the water-intoxication deaths recorded under safety signals.", "quickAnswer": "Oxytocin is the active ingredient in FDA-approved drug products, and every approved indication is obstetric. Drugs@FDA lists five oxytocin applications with prescription-status products — Pitocin (NDA 018261), NDA 018243, NDA 018248, ANDA 200219 and ANDA 091676 — and every one of them is an injectable. The FDA-approved Pitocin labeling indicates it for initiation or improvement of uterine contractions to achieve vaginal delivery, for induction of labor in patients with a medical indication, for stimulation or reinforcement of labor, as adjunctive therapy in incomplete or inevitable abortion, and to produce uterine contractions during the third stage of labor and control postpartum bleeding or hemorrhage. There is no approved indication for bonding, trust, intimacy, social anxiety, autism or postpartum depression. That same labeling states that 'Since the available data are inadequate to evaluate the benefits-to-risks considerations, Pitocin is not indicated for elective induction of labor', and warns that when given for induction or augmentation it 'should be administered only by the intravenous route and with adequate medical supervision in a hospital'. No FDA-approved intranasal oxytocin product exists: the only one FDA ever approved, Syntocinon nasal spray (NDA 12-285), had its approval withdrawn effective 8 September 1997 at the holder's request after the product was no longer marketed, and the Syntocinon injection (NDA 18-245) was withdrawn the same way effective 18 June 2009. Peptides101 has not assigned an evidence tier to oxytocin, because the Pitocin label carries no Clinical Studies section and names no pivotal efficacy trial, and we do not assign tiers we cannot show our work for.", "fdaStatus": { "value": "approved", "note": "APPROVED, and the word is doing less work than it looks. Drugs@FDA returns nine applications containing oxytocin as an active ingredient. Five carry products in 'Prescription' marketing status: NDA 018261 (PITOCIN, PH Health), NDA 018243 (Hikma), NDA 018248 (Fresenius Kabi USA), ANDA 200219 (Hikma Farmaceutica) and ANDA 091676 (Sagent). Every one of them is an INJECTABLE. Four are discontinued, and two of those four had their approvals affirmatively WITHDRAWN by Federal Register notice — the Syntocinon nasal spray in 1997 and the Syntocinon injection in 2009, both recorded with their own sources under fdaFindings. So the status of this molecule is genuinely split by route: approved as an injection, and no approved product of any kind for the intranasal route where the consumer market lives. A single 'FDA-approved' badge cannot express that, which is why this note exists. QUERY METHOD, recorded because it changes the answer: searching openfda.generic_name returns only 3 of these 9 applications and silently drops both Syntocinon records. The active-ingredient field was used instead. A short count from the openfda block is an artifact of the query, not a fact about the database.", "source": { "url": "https://api.fda.gov/drug/drugsfda.json?search=products.active_ingredients.name:%22OXYTOCIN%22&limit=100", "title": "Drugs@FDA — applications containing the active ingredient OXYTOCIN (openFDA API)", "publisher": "FDA", "date": "2026-07-31" }, "verifiedAt": "2026-08-02" }, "compoundingStatus": null, "evidence": { "tier": "verification-pending", "pendingReason": "Not assigned, and the reason is specific rather than a shrug. The usual shortcut for an FDA-approved drug is to read the pivotal trials out of the label — for oxytocin that shortcut is unavailable, because the FDA-approved Pitocin labeling has NO Clinical Studies section and names no pivotal efficacy trial. Its entire REFERENCES list is four Am J Obstet Gynecol papers from 1982-1984 by Seitchik and colleagues plus a 1987 ACOG technical bulletin. Those four were looked up in PubMed on 2026-08-02 and are indexed as Journal Article and Comparative Study — none is indexed as a randomised controlled trial. Drugs@FDA further records the original Pitocin application as approved 1980-11-19 under classification 'Type 5 - New Formulation or New Manufacturer', which is not the route by which a molecule's efficacy is first established. We therefore cannot yet name, open and administration-check an adequate and well-controlled trial establishing efficacy for the approved obstetric indications, and we will not assign a tier we cannot show our work for. READ THIS PRECISELY, BECAUSE IT WILL BE MISREAD IN BOTH DIRECTIONS. This is a statement about the state of OUR verification. It is not a claim that oxytocin does not work: FDA approved these products and continues to approve them, which is a regulatory finding of substantial evidence, and it is recorded and sourced above. Equally, it is not a licence to assume the approval covers anything outside the label. One trial HAS been opened and checked in full, and it runs against the use this compound is actually marketed for: SOARS-B (NCT01944046), a placebo-controlled trial in which intranasal oxytocin was administered to 290 children and adolescents with autism spectrum disorder, reported a p value of 0.503 on its primary social-reciprocity outcome. That trial, its administration check and its result are recorded with their own source in the FAQs below." }, "fdaApproval": { "applicationNumber": "NDA 018261 (Pitocin, PH Health); NDA 018243 (Hikma); NDA 018248 (Fresenius Kabi USA); ANDA 200219 (Hikma Farmaceutica); ANDA 091676 (Sagent) — all injectable", "brandName": "Pitocin", "approvedIndication": "IMPORTANT NOTICE — Elective induction of labor is defined as the initiation of labor in a pregnant individual who has no medical indications for induction. Since the available data are inadequate to evaluate the benefits-to-risks considerations, Pitocin is not indicated for elective induction of labor. Antepartum — Pitocin is indicated for the initiation or improvement of uterine contractions, where this is desirable and considered suitable for reasons of fetal or maternal concern, in order to achieve vaginal delivery. It is indicated for (1) induction of labor in patients with a medical indication for the initiation of labor, such as Rh problems, maternal diabetes, preeclampsia at or near term, when delivery is in the best interests of mother and fetus or when membranes are prematurely ruptured and delivery is indicated; (2) stimulation or reinforcement of labor, as in selected cases of uterine inertia; (3) as adjunctive therapy in the management of incomplete or inevitable abortion. In the first trimester, curettage is generally considered primary therapy. In second trimester abortion, oxytocin infusion will often be successful in emptying the uterus. Other means of therapy, however, may be required in such cases. Postpartum — Pitocin is indicated to produce uterine contractions during the third stage of labor and to control postpartum bleeding or hemorrhage.", "discontinued": false, "source": { "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/018261Orig1s041lbl.pdf", "title": "PITOCIN (oxytocin injection, USP) — FDA-approved labeling, NDA 018261, supplement 041", "publisher": "FDA", "date": "2021-05-11" }, "verifiedAt": "2026-08-02" }, "fdaFindings": [ { "finding": "The FDA-approved Pitocin labeling states that elective induction of labor is the initiation of labor in a pregnant individual who has no medical indications for induction, and that since the available data are inadequate to evaluate the benefits-to-risks considerations, Pitocin is not indicated for elective induction of labor.", "note": "The most-cited sentence in this label and the most-misdescribed. It is not a finding that elective induction is harmful. FDA's stated ground is evidentiary — 'the available data are inadequate to evaluate the benefits-to-risks considerations' — which is a statement about the absence of evidence, and this site does not convert an absence into a finding in either direction. Worth knowing that obstetric practice and this paragraph are not in step: elective induction at term is common, and the labelling has not been revised to bless it. That gap is real, it is between a label and a practice, and adjudicating it is a matter for clinicians and for FDA, not for this record.", "source": { "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/018261Orig1s041lbl.pdf", "title": "PITOCIN (oxytocin injection, USP) — FDA-approved labeling, NDA 018261, supplement 041", "publisher": "FDA", "date": "2021-05-11", "quote": "IMPORTANT NOTICE Elective induction of labor is defined as the initiation of labor in a pregnant individual who has no medical indications for induction. Since the available data are inadequate to evaluate the benefits-to-risks considerations, Pitocin is not indicated for elective induction of labor." }, "verifiedAt": "2026-08-02" }, { "finding": "The elective-induction paragraph is carried in the section that FDA's structured product labeling returns as the BOXED WARNING for Pitocin (NDA 018261), SPL version 15, effective 2026-05-06.", "note": "Recorded as a separate, separately sourced finding because the claim 'oxytocin carries a boxed warning' is repeated everywhere and is easy to state slightly wrong. What is verifiable is this: the openFDA label endpoint returns the text above in the `boxed_warning` field for all four current SPLs under NDA 018261, which means the SPL codes it as the boxed-warning section. Two precisions the shorthand loses. (1) Its heading in the printed label is 'IMPORTANT NOTICE', not 'WARNING'. (2) Its content is a NEGATIVE INDICATION resting on inadequate data, not a description of a documented harm — unlike, say, semaglutide's thyroid C-cell boxed warning, which describes a finding in rodents. Same structural position in the label, different kind of statement. The genuinely alarming material in this label is elsewhere, in ADVERSE REACTIONS and PRECAUTIONS, and is recorded under safety signals.", "source": { "url": "https://api.fda.gov/drug/label.json?search=openfda.application_number:%22NDA018261%22&limit=1", "title": "PITOCIN (oxytocin injection, USP) — current structured product labeling, NDA 018261 (openFDA API)", "publisher": "FDA", "date": "2026-05-06", "quote": "IMPORTANT NOTICE Elective induction of labor is defined as the initiation of labor in a pregnant individual who has no medical indications for induction. Since the available data are inadequate to evaluate the benefits-to-risks considerations, Pitocin is not indicated for elective induction of labor." }, "verifiedAt": "2026-08-02" }, { "finding": "FDA withdrew approval of NDA 12-285, Syntocinon (oxytocin nasal solution) Nasal Spray, effective 8 September 1997. The application holder notified FDA in writing that the product was no longer marketed and requested that approval be withdrawn, waiving the opportunity for a hearing.", "note": "THE FINDING THIS RECORD EXISTS TO PUBLISH. FDA did once approve an intranasal oxytocin product. That approval was withdrawn in 1997, and there has been no FDA-approved intranasal oxytocin product in the United States since. Every nasal oxytocin spray on the consumer market today is therefore an unapproved product, whatever else is true about it. Now read the mechanism, because the inversion is available here and sellers run it on sermorelin already. The withdrawal was REQUESTED BY THE HOLDER because the product was no longer marketed. It was not a safety finding and not an efficacy finding, and nothing in this notice says intranasal oxytocin was found dangerous. It equally says nothing good: a commercial withdrawal is the absence of an approval, not an endorsement of what replaced it. Note also what the withdrawn product was and was not. It was a prescription drug product with a label, a strength and a manufacturer. It is not the same thing as an unlabelled spray bought online, and the existence of the old approval is not retrospective cover for the new products.", "source": { "url": "https://www.federalregister.gov/documents/1997/08/07/97-20871/sterling-drug-inc-et-al-withdrawal-of-approval-of-28-new-drug-applications-9-abbreviated-antibiotic", "title": "Sterling Drug, Inc., et al.; Withdrawal of Approval of 28 New Drug Applications, 9 Abbreviated Antibiotic Applications, and 46 Abbreviated New Drug Applications (62 FR 42575)", "publisher": "FDA", "date": "1997-08-07", "quote": "The holders of the applications listed in the table in this document have informed FDA that these drug products are no longer marketed and have requested that FDA withdraw approval of the applications. … NDA 12-285 Syntocinon (oxytocin nasal solution) Nasal Spray … approval of the applications listed in the table in this document, and all amendments and supplements thereto, is hereby withdrawn, effective September 8, 1997." }, "verifiedAt": "2026-08-02" }, { "finding": "FDA withdrew approval of NDA 18-245, Syntocinon (oxytocin) Injection, Novartis Pharmaceuticals Corp., effective 18 June 2009, on the same basis — the holder notified FDA the product was no longer marketed and requested withdrawal.", "note": "Recorded so that the phrase 'Syntocinon' resolves to two different products rather than one. The nasal spray (NDA 12-285) went in 1997; the injection (NDA 18-245) went in 2009. A brand name is not a product, and 'Syntocinon' identifies neither on its own. Readers of this library will recognise the citation: 74 FR 23407 is the same Federal Register notice that withdrew sermorelin's GEREF applications, effective the same day.", "source": { "url": "https://www.federalregister.gov/documents/2009/05/19/E9-11628/novartis-pharmaceuticals-corp-et-al-withdrawal-of-approval-of-92-new-drug-applications-and-49", "title": "Novartis Pharmaceuticals Corp. et al.; Withdrawal of Approval of 92 New Drug Applications and 49 Abbreviated New Drug Applications (74 FR 23407)", "publisher": "FDA", "date": "2009-05-19", "quote": "NDA 18-245 Syntocinon (oxytocin) Injection … approval of the applications listed in the table in this document, and all amendments and supplements thereto, is hereby withdrawn, effective June 18, 2009." }, "verifiedAt": "2026-08-02" }, { "finding": "Oxytocin appears in none of Categories 1, 2 or 3 of FDA's list of bulk drug substances nominated for use in compounding under section 503A, updated 2026-05-14.", "note": "Recorded to close a misreading, not to assert a status — which is why this record carries no compoundingStatus field at all. Verified by fetching the document with a browser user-agent and text-extracting it locally on 2026-08-02: zero hits for 'oxytocin' anywhere in seven pages. This absence means something different from BPC-157's absence. BPC-157 was nominated and left Category 2 when the nominators withdrew. Oxytocin was never in this system: a 503A bulks nomination is a route for substances WITHOUT an approved product, and oxytocin has five marketed applications. Categorical silence here is neither permission nor a safety finding, and it answers no question about whether any particular compounded oxytocin preparation is lawful — that turns on other parts of section 503A which this record does not reach.", "source": { "url": "https://www.fda.gov/media/94155/download", "title": "Bulk Drug Substances Nominated for Use in Compounding Under Section 503A of the Federal Food, Drug, and Cosmetic Act", "publisher": "FDA", "date": "2026-05-14" }, "verifiedAt": "2026-08-02" }, { "finding": "The FDA-approved Pitocin labeling contains no Clinical Studies section. Its entire REFERENCES list is four Am J Obstet Gynecol papers published 1982-1984 and one 1987 ACOG technical bulletin.", "note": "This is why this record's evidence tier is verification-pending, and it is a fact about the label rather than a criticism of the drug. There is no section of this label from which a pivotal trial can be read. The four papers were looked up in PubMed on 2026-08-02. All four are real, all four administered oxytocin to labouring women, and none is indexed as a randomised controlled trial — PubMed's publication types are Journal Article and, for two of them, Comparative Study. A small sourcing error found by opening them, recorded because this site's whole method is opening the citation: the label's second reference is numbered 'II. Multiparous patients'. Volume and pages (145:777-780) are correct, but the paper at that citation is numbered III in the series; part II is 'Uterine activity data', 145:526-529. The roman numeral in the label is wrong. Nothing turns on it — it is reported because a library that only reports the errors it finds in other people's documents is not doing the check.", "source": { "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/018261Orig1s041lbl.pdf", "title": "PITOCIN (oxytocin injection, USP) — FDA-approved labeling, NDA 018261, supplement 041", "publisher": "FDA", "date": "2021-05-11", "quote": "REFERENCES Seitchik J, Castillo M: Oxytocin augmentation of dysfunctional labor. I. Clinical data. Am J Obstet Gynecol 1982; 144:899–905. Seitchik J, Castillo M: Oxytocin augmentation of dysfunctional labor. II. Multiparous patients. Am J Obstet Gynecol 1983; 145:777-780. Fuchs A, Goeschen K, Husslein P, et al: Oxytocin and the initiation of human parturition. III. … Am J Obstet Gynecol 1983; 145:497–502. Seitchik J, Amico J, et al: Oxytocin augmentation of dysfunctional labor. IV. Oxytocin pharmacokinetics. Am J Obstet Gynecol 1984; 150:225–228. American College of Obstetricians and Gynecologists: ACOG Technical Bulletin Number 110—November 1987: Induction and augmentation of labor." }, "verifiedAt": "2026-08-02" }, { "finding": "Drugs@FDA records the original Pitocin application (NDA 018261) as approved 1980-11-19 with submission classification 'Type 5 - New Formulation or New Manufacturer'.", "note": "Recorded because it explains the previous finding rather than duplicating it. A Type 5 application is a new formulation or a new manufacturer of an already-established drug — it is not the pathway on which a molecule's efficacy is established for the first time. Oxytocin's clinical use long predates this application and long predates the modern trial apparatus. The honest summary: the approval is real and current, the label has been maintained (most recently revised March 2026), and the evidentiary record that originally supported it is not something this label lets you read. Those three things are all true at once, and any account that drops one of them is selling something.", "source": { "url": "https://api.fda.gov/drug/drugsfda.json?search=products.active_ingredients.name:%22OXYTOCIN%22&limit=100", "title": "Drugs@FDA — applications containing the active ingredient OXYTOCIN (openFDA API)", "publisher": "FDA", "date": "2026-07-31" }, "verifiedAt": "2026-08-02" } ], "safetySignals": [ { "signal": "The FDA-approved Pitocin labeling restricts route and setting: Pitocin, when given for induction of labor or augmentation of uterine activity, should be administered only by the intravenous route and with adequate medical supervision in a hospital.", "note": "The entire WARNINGS section of this label is that one sentence, and it is the sentence furthest from how the consumer market uses this molecule. The approved product is restricted to a route (intravenous), a setting (hospital) and a condition (adequate medical supervision). Read the scope honestly: the sentence is written about induction and augmentation of labour, which is what the label covers. It is not a finding about intranasal oxytocin for social use, because FDA has not made one. What it does establish is that FDA's own risk assessment of oxytocin was made on the assumption of continuous professional monitoring — and the PRECAUTIONS section spells out why, requiring 'continuous observation by trained personnel' and a physician qualified to manage complications 'immediately available'. None of that assumption survives contact with a spray bottle bought online.", "source": { "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/018261Orig1s041lbl.pdf", "title": "PITOCIN (oxytocin injection, USP) — FDA-approved labeling, NDA 018261, supplement 041", "publisher": "FDA", "date": "2021-05-11", "quote": "WARNINGS Pitocin, when given for induction of labor or augmentation of uterine activity, should be administered only by the intravenous route and with adequate medical supervision in a hospital." }, "verifiedAt": "2026-08-02" }, { "signal": "Adverse reactions reported in the mother in the FDA-approved Pitocin labeling include anaphylactic reaction, premature ventricular contractions, postpartum hemorrhage, pelvic hematoma, cardiac arrhythmia, subarachnoid hemorrhage, fatal afibrinogenemia, hypertensive episodes, nausea, rupture of the uterus and vomiting. The labeling states that severe water intoxication with convulsions and coma has occurred, and that maternal death due to oxytocin-induced water intoxication has been reported.", "note": "Reproduced because 'it's just a natural hormone' is doing enormous work in this market. The water-intoxication mechanism is the one worth understanding rather than memorising: the label states elsewhere that oxytocin 'has been shown to have an intrinsic antidiuretic effect, acting to increase water reabsorption from the glomerular filtrate', which it attributes to oxytocin and vasopressin differing at only two of eight amino acid positions. That is a property of the molecule, not of the obstetric setting. QUOTE HANDLING: FDA's sentence names an infusion duration alongside the description of the infusion. It is truncated with an ellipsis under this site's no-dosing policy. No finding depends on the elided words — the deaths are the finding.", "source": { "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/018261Orig1s041lbl.pdf", "title": "PITOCIN (oxytocin injection, USP) — FDA-approved labeling, NDA 018261, supplement 041", "publisher": "FDA", "date": "2021-05-11", "quote": "The following adverse reactions have been reported in the mother: Anaphylactic reaction … Subarachnoid hemorrhage … Fatal afibrinogenemia … Rupture of the uterus … Severe water intoxication with convulsions and coma has occurred, associated with a slow oxytocin infusion… Maternal death due to oxytocin-induced water intoxication has been reported." }, "verifiedAt": "2026-08-02" }, { "signal": "Adverse reactions reported in the fetus or neonate in the FDA-approved Pitocin labeling include bradycardia, premature ventricular contractions and other arrhythmias, permanent CNS or brain damage, fetal death, low Apgar scores at five minutes, neonatal jaundice, neonatal retinal hemorrhage and neonatal seizures.", "note": "Recorded separately from the maternal list because the label separates them, and because the label attributes them to two distinct causes it names in its own headings: 'Due to induced uterine motility' and 'Due to use of oxytocin in the mother'. The PRECAUTIONS section adds that 'Maternal deaths due to hypertensive episodes, subarachnoid hemorrhage, rupture of the uterus, and fetal deaths due to various causes have been reported associated with the use of parenteral oxytocic drugs for induction of labor or for augmentation in the first and second stages of labor.' These are labeled reactions in a supervised hospital setting, reported to a manufacturer under a regulatory duty. There is no equivalent reporting channel for an unapproved nasal spray, which means the absence of comparable reports about those products is not information.", "source": { "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/018261Orig1s041lbl.pdf", "title": "PITOCIN (oxytocin injection, USP) — FDA-approved labeling, NDA 018261, supplement 041", "publisher": "FDA", "date": "2021-05-11", "quote": "The following adverse reactions have been reported in the fetus or neonate: Due to induced uterine motility: … Bradycardia … Permanent CNS or brain damage … Fetal death … Neonatal seizures have been reported with the use of Pitocin." }, "verifiedAt": "2026-08-02" }, { "signal": "The FDA-approved Pitocin labeling states there are no animal or human studies on the carcinogenicity and mutagenicity of oxytocin, nor any information on its effect on fertility, and that animal reproduction studies have not been conducted with oxytocin.", "note": "A blank in FDA's own document, recorded as a blank. This is tolerable for a drug given over hours in a delivery room and evaluated on that basis — the label's own reasoning for the absence of teratogenicity data is that there are 'no known indications for use in the first trimester of pregnancy other than in relation to spontaneous or induced abortion'. It is a materially different blank for a product taken repeatedly over months or years, which is what the bonding and social-anxiety market is. The approved label's silence on long-term exposure is not reassurance about long-term exposure; it is the consequence of a short-exposure indication. Nobody has run those studies because the approved use never required them.", "source": { "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/018261Orig1s041lbl.pdf", "title": "PITOCIN (oxytocin injection, USP) — FDA-approved labeling, NDA 018261, supplement 041", "publisher": "FDA", "date": "2021-05-11", "quote": "There are no animal or human studies on the carcinogenicity and mutagenicity of this drug, nor is there any information on its effect on fertility. … Animal reproduction studies have not been conducted with oxytocin." }, "verifiedAt": "2026-08-02" } ], "faqs": [ { "question": "Is oxytocin FDA-approved for bonding, trust, or social anxiety?", "answer": "No. Every indication in the FDA-approved labeling for Pitocin (oxytocin injection, USP, NDA 018261) is obstetric. The label indicates it for the initiation or improvement of uterine contractions in order to achieve vaginal delivery, for induction of labor in patients with a medical indication such as Rh problems, maternal diabetes or preeclampsia at or near term, for stimulation or reinforcement of labor in selected cases of uterine inertia, as adjunctive therapy in the management of incomplete or inevitable abortion, and to produce uterine contractions during the third stage of labor and to control postpartum bleeding or hemorrhage. Bonding, attachment, trust, intimacy, social anxiety, autism, postpartum depression and milk letdown appear nowhere in it. Those uses are not narrower or broader readings of the approved indication — they are absent from the document. Note also the route: the approved products are injections given in hospital, so a nasal spray or sublingual troche sold for any of those purposes is not the approved product, and this approval says nothing about it.", "source": { "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/018261Orig1s041lbl.pdf", "title": "PITOCIN (oxytocin injection, USP) — FDA-approved labeling, NDA 018261, supplement 041", "publisher": "FDA", "date": "2021-05-11", "quote": "Antepartum: Pitocin is indicated for the initiation or improvement of uterine contractions, where this is desirable and considered suitable for reasons of fetal or maternal concern, in order to achieve vaginal delivery. … Postpartum: Pitocin is indicated to produce uterine contractions during the third stage of labor and to control postpartum bleeding or hemorrhage." }, "verifiedAt": "2026-08-02" }, { "question": "Is oxytocin nasal spray FDA-approved?", "answer": "No, and it has not been since 1997. FDA did once approve an intranasal oxytocin product — Syntocinon (oxytocin nasal solution) Nasal Spray, NDA 12-285. FDA withdrew approval of that application effective 8 September 1997, by notice published at 62 FR 42575, after the holder notified the agency in writing that the product was no longer marketed and requested withdrawal. There has been no FDA-approved intranasal oxytocin product in the United States since. Every oxytocin nasal spray on the consumer market today is therefore an unapproved product. Read the mechanism of the withdrawal carefully in both directions, because it is easy to spin: it was a commercial withdrawal at the sponsor's request, so it is not a finding that intranasal oxytocin is dangerous — and equally, an approval that was surrendered is the absence of an approval, not an endorsement of the products that filled the gap. Drugs@FDA still lists NDA 012285 with its product in 'Discontinued' marketing status, which is why a database lookup alone will not tell you the approval was withdrawn; the Federal Register notice will.", "source": { "url": "https://www.federalregister.gov/documents/1997/08/07/97-20871/sterling-drug-inc-et-al-withdrawal-of-approval-of-28-new-drug-applications-9-abbreviated-antibiotic", "title": "Sterling Drug, Inc., et al.; Withdrawal of Approval of 28 New Drug Applications, 9 Abbreviated Antibiotic Applications, and 46 Abbreviated New Drug Applications (62 FR 42575)", "publisher": "FDA", "date": "1997-08-07", "quote": "NDA 12-285 Syntocinon (oxytocin nasal solution) Nasal Spray … approval of the applications listed in the table in this document, and all amendments and supplements thereto, is hereby withdrawn, effective September 8, 1997." }, "verifiedAt": "2026-08-02" }, { "question": "Does intranasal oxytocin help children with autism?", "answer": "The largest placebo-controlled trial to report on that question did not find a benefit on its primary outcome. In SOARS-B (NCT01944046), a Phase 2 double-blind trial of 290 children and adolescents with autism spectrum disorder, investigators randomised participants to an intranasal oxytocin spray or to a matched placebo spray containing every other ingredient in the same quantities, and measured change on the Aberrant Behavior Checklist modified social withdrawal subscale over a 24-week double-blind phase. The posted results report a p value of 0.503 for oxytocin versus placebo on that primary outcome, by mixed-models analysis adjusted for baseline, age category and functionality category; a 24-week open-label extension likewise reported no significant difference between the original assignment groups (p = 0.61). This is a genuine human administration trial, not an endogenous-biomarker study: intranasal oxytocin was given to participants, the registration records the intervention type as DRUG, the trial is completed, and results are posted rather than absent. One Phase 2 trial in one population is not the last word on intranasal oxytocin, but it is the best-powered answer currently posted to this question, and it is negative.", "source": { "url": "https://clinicaltrials.gov/study/NCT01944046", "title": "SOARS-B — Phase II Study of Oxytocin in Autism to Improve Reciprocal Social Behaviors (NCT01944046)", "publisher": "ClinicalTrials.gov", "date": "2021-01-05", "quote": "Change in Aberrant Behavior Checklist-Modified Social Withdrawal Subscale ABC-mSW, a Measure of Social Reciprocity … p-Value 0.503 … Mixed Models Analysis … adjusted for baseline, age category, functionality category" }, "verifiedAt": "2026-08-02" }, { "question": "Why does the Pitocin label say it is not indicated for elective induction of labor?", "answer": "Because FDA's stated ground is that the evidence is insufficient, not that the practice is harmful. The FDA-approved Pitocin labeling opens its INDICATIONS AND USAGE section with an 'IMPORTANT NOTICE' defining elective induction as 'the initiation of labor in a pregnant individual who has no medical indications for induction' and stating: 'Since the available data are inadequate to evaluate the benefits-to-risks considerations, Pitocin is not indicated for elective induction of labor.' FDA's structured product labeling carries that paragraph in the section coded as the label's boxed warning. Two things follow and neither is what the sentence is usually taken to mean. It is a statement about missing data, so it is not a finding that oxytocin causes harm in elective induction. And it is a negative indication, so it does not make elective induction unlawful — prescribing outside a labeled indication is a decision for a licensed clinician, and it is simply a use this label does not support.", "source": { "url": "https://api.fda.gov/drug/label.json?search=openfda.application_number:%22NDA018261%22&limit=1", "title": "PITOCIN (oxytocin injection, USP) — current structured product labeling, NDA 018261 (openFDA API)", "publisher": "FDA", "date": "2026-05-06", "quote": "IMPORTANT NOTICE Elective induction of labor is defined as the initiation of labor in a pregnant individual who has no medical indications for induction. Since the available data are inadequate to evaluate the benefits-to-risks considerations, Pitocin is not indicated for elective induction of labor." }, "verifiedAt": "2026-08-02" }, { "question": "Is oxytocin on FDA's 503A bulk drug substances list?", "answer": "No. Oxytocin appears in none of Categories 1, 2 or 3 of FDA's list of bulk drug substances nominated for use in compounding under section 503A, updated 14 May 2026 — verified by fetching that document and searching its full text, which returns zero hits for the word. That absence means something different from BPC-157's absence, and conflating the two is the most common error in this area. BPC-157 was nominated, sat in Category 2, and left the list when the nominators withdrew their nominations. Oxytocin was never in this system at all: a 503A bulks nomination is a route for substances that have no FDA-approved product, and oxytocin has five applications with prescription-status products in Drugs@FDA. Categorical silence here is neither permission nor a safety finding, and it does not answer whether any particular compounded oxytocin preparation is lawful — that question turns on other parts of section 503A that this record does not reach.", "source": { "url": "https://www.fda.gov/media/94155/download", "title": "Bulk Drug Substances Nominated for Use in Compounding Under Section 503A of the Federal Food, Drug, and Cosmetic Act", "publisher": "FDA", "date": "2026-05-14" }, "verifiedAt": "2026-08-02" }, { "question": "What are the labeled risks of oxytocin?", "answer": "Serious ones, and they are recorded in FDA's own approved labeling rather than inferred. The Pitocin label lists adverse reactions reported in the mother including anaphylactic reaction, subarachnoid hemorrhage, fatal afibrinogenemia, cardiac arrhythmia, hypertensive episodes, postpartum hemorrhage, pelvic hematoma and rupture of the uterus, and states that severe water intoxication with convulsions and coma has occurred and that maternal death due to oxytocin-induced water intoxication has been reported. In the fetus or neonate it lists bradycardia, arrhythmias, low Apgar scores at five minutes, neonatal jaundice, neonatal retinal hemorrhage, neonatal seizures, permanent CNS or brain damage and fetal death. The label's PRECAUTIONS section adds that maternal deaths due to hypertensive episodes, subarachnoid hemorrhage and uterine rupture, and fetal deaths due to various causes, have been reported in association with parenteral oxytocic drugs used for induction or augmentation of labor. Two framing points. These reactions are described for an intravenous product given under continuous professional monitoring — the label's entire WARNINGS section requires exactly that — so they are not a direct read-across to any other route. And the label separately states there are no animal or human studies on the carcinogenicity and mutagenicity of oxytocin, nor any information on its effect on fertility, which is a blank rather than a clean result.", "source": { "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/018261Orig1s041lbl.pdf", "title": "PITOCIN (oxytocin injection, USP) — FDA-approved labeling, NDA 018261, supplement 041", "publisher": "FDA", "date": "2021-05-11", "quote": "The following adverse reactions have been reported in the mother: Anaphylactic reaction … Subarachnoid hemorrhage … Fatal afibrinogenemia … Rupture of the uterus … Maternal death due to oxytocin-induced water intoxication has been reported." }, "verifiedAt": "2026-08-02" }, { "question": "Does the Pitocin label name the clinical trials the approval was based on?", "answer": "No. The FDA-approved Pitocin labeling has no Clinical Studies section, and its entire REFERENCES list is four Am J Obstet Gynecol papers published between 1982 and 1984 — three by Seitchik and colleagues on oxytocin augmentation of dysfunctional labor, one by Fuchs and colleagues on the initiation of human parturition — plus ACOG Technical Bulletin Number 110 from November 1987. None of the five is identified in the label as a trial supporting the approval, and the label contains no section in which such a trial could be described. Drugs@FDA records the original application as approved on 19 November 1980 under the classification 'Type 5 - New Formulation or New Manufacturer', which is not the pathway on which a molecule's efficacy is established for the first time. That is why this record carries no evidence tier: we could not name and open an adequate, well-controlled efficacy trial for the approved indications, and we do not assign ratings we cannot show our work for. It is not a claim that oxytocin does not work — FDA's approval stands and the label is actively maintained, most recently revised in March 2026.", "source": { "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/018261Orig1s041lbl.pdf", "title": "PITOCIN (oxytocin injection, USP) — FDA-approved labeling, NDA 018261, supplement 041", "publisher": "FDA", "date": "2021-05-11", "quote": "REFERENCES Seitchik J, Castillo M: Oxytocin augmentation of dysfunctional labor. I. Clinical data. Am J Obstet Gynecol 1982; 144:899–905. … American College of Obstetricians and Gynecologists: ACOG Technical Bulletin Number 110—November 1987: Induction and augmentation of labor." }, "verifiedAt": "2026-08-02" } ] }, { "slug": "pt-141", "name": "PT-141 (Bremelanotide)", "aliases": [ "PT-141", "Bremelanotide", "Bremelanotide acetate", "Vyleesi", "PT 141" ], "url": "https://peptides101.com/compounds/pt-141", "moleculeNote": "Per the FDA label's Description section: bremelanotide acetate is a synthetic, cyclic heptapeptide, Ac-Nle-cyclo-(Asp-His-D-Phe-Arg-Trp-Lys-OH), molecular weight 1025.2 (free base). It is a melanocortin receptor agonist that NONSELECTIVELY activates several receptor subtypes, in the label's stated order of potency: MC1R, MC4R, MC3R, MC5R, MC2R. That nonselectivity is not trivia — MC1R is expressed on melanocytes, and the label draws the causal line itself: binding there 'leads to melanin expression and increased pigmentation'. The hyperpigmentation signal below is the mechanism working as designed, not an idiosyncratic reaction. The label does not describe bremelanotide as a metabolite or derivative of melanotan II; that widely repeated lineage claim is not sourced here because it was not verified against a primary document.", "quickAnswer": "PT-141 (bremelanotide) is an FDA-approved prescription drug — VYLEESI, NDA 210557, approved 21 June 2019, and shown on Drugs@FDA with marketing status 'Prescription' — but solely for premenopausal women with acquired, generalized hypoactive sexual desire disorder, and its FDA label states verbatim that it is 'not indicated for the treatment of HSDD in postmenopausal women or in men' and 'not indicated to enhance sexual performance'. In the two pivotal Phase 3 trials behind that approval, FDA reports no significant difference between VYLEESI and placebo in the number of satisfying sexual events, a secondary endpoint; the two co-primary endpoints that did separate from placebo were both questionnaires — self-rated sexual desire and self-rated distress about low desire — and nausea was reported in 40% of VYLEESI-treated patients versus 1% on placebo.", "fdaStatus": { "value": "approved", "note": "FDA-approved. Approval is always for a specific indication and population — see the approval record below, because it is routinely not the use this is marketed for.", "source": { "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/210557s000lbl.pdf", "title": "VYLEESI (bremelanotide) injection — Highlights of Prescribing Information, original approval", "publisher": "FDA", "date": "2019-06-21" }, "verifiedAt": "2026-07-16" }, "compoundingStatus": null, "evidence": { "tier": "proven-in-humans", "humanAdministrationChecked": true, "note": "ADMINISTRATION CHECK PASSED, and passed decisively — this is the rare record where it does. Both pivotal trials are interventional studies in which bremelanotide was self-administered by subcutaneous injection against placebo. Neither measures an endogenous peptide as a biomarker, which is the failure mode that reduces MOTS-c's and TB-500's apparent human trial counts to zero. Both were checked against the ClinicalTrials.gov v2 API on 2026-07-16: NCT02333071 (n=723 actual) and NCT02338960 (n=714 actual), lead sponsor Palatin Technologies, both COMPLETED with results posted. None of the contamination markers in this vertical are present — not the single research-peptide vendor sponsor, not the Feb-2026 start, not the perpetual RECRUITING status, not the zero-results registrations. THE TIER IS EARNED, AND IT IS ALSO NARROW. Scope: efficacy is established for premenopausal women with acquired, generalized HSDD and for nothing else. There is no tier here for men, for postmenopausal women, or for sexual performance — the label excludes all three, and absence of an approved indication is not evidence of efficacy awaiting discovery. Magnitude: in FDA's own Clinical Studies section, the co-primary FSFI-Desire endpoint (scale 1.2-6.0) improved by a mean of 0.5 vs 0.2 for placebo in Study 1 and 0.6 vs 0.2 in Study 2 — a placebo-subtracted difference of roughly 0.3-0.4 points on a 4.8-point scale. Statistically significant (p=0.0002 and p<0.0001, unadjusted Wilcoxon rank-sum) and small. 'Proven in humans' here means 'beat placebo on a questionnaire by a modest margin in two adequate trials', which is what drug approval means and is less than what the word 'proven' is doing in vendor copy.", "source": { "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/210557s000lbl.pdf", "title": "VYLEESI (bremelanotide) injection — Highlights of Prescribing Information, original approval", "publisher": "FDA", "date": "2019-06-21" }, "verifiedAt": "2026-07-16" }, "fdaApproval": { "applicationNumber": "NDA 210557", "brandName": "VYLEESI", "approvedIndication": "VYLEESI is indicated for the treatment of premenopausal women with acquired, generalized hypoactive sexual desire disorder (HSDD), as characterized by low sexual desire that causes marked distress or interpersonal difficulty and is NOT due to: A co-existing medical or psychiatric condition, Problems with the relationship, or The effects of a medication or drug substance.", "discontinued": false, "source": { "url": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=f1d0c1b5-2f39-4bad-a6a4-0066e3ad5dcf", "title": "VYLEESI (bremelanotide) injection, solution — Prescribing Information (current SPL)", "publisher": "DailyMed (U.S. National Library of Medicine)", "date": "2025-11-13", "quote": "Limitations of Use: VYLEESI is not indicated for the treatment of HSDD in postmenopausal women or in men. VYLEESI is not indicated to enhance sexual performance." }, "verifiedAt": "2026-07-16" }, "fdaFindings": [ { "finding": "FDA states on the approved label that the mechanism by which VYLEESI improves HSDD in women is unknown.", "note": "Approval establishes that a drug worked in trials, not that anyone knows why. This sits directly against the mechanistic storytelling the compound is marketed with — an approved drug whose own label declines to claim a mechanism is a poor foundation for a vendor's mechanistic extrapolation to populations and uses the label excludes.", "source": { "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/210557s000lbl.pdf", "title": "VYLEESI (bremelanotide) injection — Highlights of Prescribing Information, original approval", "publisher": "FDA", "date": "2019-06-21", "quote": "The mechanism by which VYLEESI improves HSDD in women is unknown." }, "verifiedAt": "2026-07-16" }, { "finding": "FDA reports on the approved label that the two pivotal Phase 3 trials found no significant difference between VYLEESI and placebo in the number of satisfying sexual events.", "note": "THE MOST CITABLE SENTENCE ON THIS RECORD, and the one the compound's marketing cannot survive. PT-141 is sold on the promise of more and better sex. In the trials that won the approval that marketing invokes, the endpoint that counts sexual events did not separate from placebo. What did separate were two questionnaire endpoints — self-rated desire and self-rated distress about low desire. That is the approved effect: patients reported wanting sex more and being less bothered by not wanting it, without the trial detecting more satisfying sex. Re-verified verbatim against the current SPL via the openFDA label API on 2026-07-16 (effective_time 20251113); the sentence is unchanged since approval. It is a secondary endpoint and a null result on one is not proof of absence — but it is FDA's own reported result on the outcome the customer is actually buying, and no vendor citing 'FDA-approved' will ever reproduce it.", "source": { "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/210557s000lbl.pdf", "title": "VYLEESI (bremelanotide) injection — Highlights of Prescribing Information, original approval", "publisher": "FDA", "date": "2019-06-21", "quote": "There was no significant difference between treatment groups in the change from baseline to end of study visit in the number of satisfying sexual events (SSEs), a secondary endpoint." }, "verifiedAt": "2026-07-16" }, { "finding": "FDA reports on the approved label that in both pivotal trials VYLEESI showed a statistically significant increase in the FSFI Desire Domain score and a statistically significant decrease in the FSDS-DAO Q13 score — the two co-primary endpoints, both patient questionnaires — from baseline to the end-of-study visit compared to placebo.", "note": "This is the positive finding, recorded as carefully as the negative one above it, and it is what the approval rests on. Read the endpoints for what the label says they are. FSFI-Desire is two questions — the label quotes them: 'Over the past 4 weeks, how often did you feel sexual desire or interest?' and a rating of the level of that desire. FSDS-DAO Q13 is one question: 'How often did you feel: Bothered by low sexual desire?' So both co-primary endpoints are self-report about desire, and the endpoint that counted sexual events did not separate (see the finding above). That is not a criticism of the trials — HSDD is a disorder of desire and distress, so measuring desire and distress is the correct design. It is a caution against reading 'two positive Phase 3 trials' as evidence of anything a customer buying a sexual-performance compound is trying to buy.", "source": { "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/210557s000lbl.pdf", "title": "VYLEESI (bremelanotide) injection — Highlights of Prescribing Information, original approval", "publisher": "FDA", "date": "2019-06-21", "quote": "In both studies, VYLEESI showed a statistically significant increase in the FSFI Desire Domain score and a statistically significant decrease in the FSDS-DAO Q13 score from baseline to the EOS visit compared to placebo." }, "verifiedAt": "2026-07-16" }, { "finding": "Drugs@FDA shows NDA 210557 with original submission ORIG-1 approved 21 June 2019, sponsor Cosette, and VYLEESI (autoinjector) with marketing status 'Prescription'.", "note": "Recorded as its own finding rather than asserted inside a note, because two facts this record leans on are not in the label and cannot be: that the product is still marketed, and that the application now sits with Cosette Pharmaceuticals rather than the AMAG or Palatin sponsors the secondary corpus still names. The query returns exactly one result — there is no second bremelanotide application, and no generic. 'Prescription' is the whole of the drug's lawful supply route: every unit lawfully in the United States is dispensed by a pharmacy against a prescription for this one product. Re-run the URL to re-verify; it is a live query, not a PDF.", "source": { "url": "https://api.fda.gov/drug/drugsfda.json?search=openfda.generic_name:\"bremelanotide\"+OR+products.active_ingredients.name:\"BREMELANOTIDE+ACETATE\"&limit=5", "title": "Drugs@FDA — approved drug products database, queried for bremelanotide (openFDA)", "publisher": "FDA", "date": "2026-07-16", "quote": "\"application_number\": \"NDA210557\", \"sponsor_name\": \"COSETTE\" … \"brand_name\": \"VYLEESI (AUTOINJECTOR)\" … \"marketing_status\": \"Prescription\"" }, "verifiedAt": "2026-07-16" }, { "finding": "FDA reports that 40% of VYLEESI patients prematurely discontinued the 24-week double-blind period in Study 1 versus 13% on placebo, and 39% versus 25% in Study 2.", "note": "Read this against the effect size in `evidence`. Four in ten participants on drug did not finish the trial — three times the placebo rate in Study 1 — and FDA says so while explaining why an extra analysis was needed. Differential dropout of that magnitude, concentrated in the treated arm and driven substantially by tolerability (18% discontinued for adverse reactions vs 2% on placebo, see safetySignals), is a known source of bias in the surviving completers' self-reported scores. FDA approved the drug on these trials, so this is not an argument that the result is invalid. It is the texture that 'two positive Phase 3 trials' erases. Confirmed present verbatim in the current SPL (openFDA label API, 2026-07-16).", "source": { "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/210557s000lbl.pdf", "title": "VYLEESI (bremelanotide) injection — Highlights of Prescribing Information, original approval", "publisher": "FDA", "date": "2019-06-21", "quote": "Because a greater percentage of MITT patients in the VYLEESI group prematurely discontinued the 24-week double-blind treatment period compared to placebo patients (40% vs. 13% for Study 1 and 39% vs. 25% for Study 2), an exploratory analysis was performed examining the percentages of patients who were able to complete the treatment period and improved from baseline." }, "verifiedAt": "2026-07-16" }, { "finding": "The label directs patients to avoid using VYLEESI with an orally administered naltrexone-containing product intended to treat alcohol or opioid addiction, citing the severe consequence of naltrexone treatment failure.", "note": "A documented interaction in which the failure mode is not a side effect of bremelanotide but the silent failure of a different, load-bearing drug — one whose failure means relapse. It is here because it is the interaction least likely to be caught outside a prescription: the label surfaces it in Highlights, and a person buying a research chemical has no prescriber cross-checking their naltrexone. Still present in the current SPL's Drug Interactions section (openFDA label API, 2026-07-16).", "source": { "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/210557s000lbl.pdf", "title": "VYLEESI (bremelanotide) injection — Highlights of Prescribing Information, original approval", "publisher": "FDA", "date": "2019-06-21", "quote": "As VYLEESI may significantly decrease the systemic exposure of orally-administered naltrexone, patients should avoid using VYLEESI with an orally administered naltrexone-containing product that is intended to treat alcohol and opioid addiction due to the severe consequence of naltrexone treatment failure." }, "verifiedAt": "2026-07-16" }, { "finding": "FDA states on the label that the safety and effectiveness of VYLEESI have not been established in pediatric patients or in geriatric patients.", "note": "The label carries the identical sentence for geriatric patients. Together with the Limitations of Use, the population in which anything is established narrows to exactly one: premenopausal adult women with acquired, generalized HSDD. Everyone else buying this compound is outside the evidence base, not merely outside the marketing approval.", "source": { "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/210557s000lbl.pdf", "title": "VYLEESI (bremelanotide) injection — Highlights of Prescribing Information, original approval", "publisher": "FDA", "date": "2019-06-21", "quote": "The safety and effectiveness of VYLEESI have not been established in pediatric patients." }, "verifiedAt": "2026-07-16" }, { "finding": "Bremelanotide appears nowhere in Categories 1, 2 or 3 of FDA's 503A bulk drug substances list (updated 2026-05-14).", "note": "READ THIS ABSENCE THE OPPOSITE WAY FROM BPC-157's. Verified by fetching and text-extracting the document directly on 2026-07-16 (Category 2 contains exactly six substances, and bremelanotide is not among them). For BPC-157, absence means the nominations were withdrawn. For bremelanotide, absence means the 503A nomination pathway was never the relevant one: that pathway exists for bulk substances that are NOT components of approved drugs, and bremelanotide is the active ingredient of an approved drug. Mapping 'not on the list' to withdrawn-from-nomination or never-nominated here would be mechanically consistent and completely wrong. This record does NOT adjudicate whether bremelanotide may lawfully be compounded — that turns on other 503A conditions, including the restriction on compounding drugs that are essentially copies of commercially available approved products, which we have not verified and therefore do not assert.", "source": { "url": "https://www.fda.gov/media/94155/download", "title": "Bulk Drug Substances Nominated for Use in Compounding Under Section 503A of the Federal Food, Drug, and Cosmetic Act", "publisher": "FDA", "date": "2026-05-14" }, "verifiedAt": "2026-07-16" } ], "safetySignals": [ { "signal": "Nausea was reported in 40% of VYLEESI-treated patients in the pooled Phase 3 placebo-controlled trials versus 1% on placebo, requiring anti-emetic therapy in 13% and causing 8% to discontinue.", "note": "The overall discontinuation rate due to adverse reactions was 18% on VYLEESI versus 2% on placebo. Roughly one in five trial participants stopped because of how the drug made them feel — in a trial population that had been screened and consented. The 2019 label's guidance on this is to consider discontinuing VYLEESI for persistent or severe nausea, or initiating anti-emetic therapy for patients who are bothered by nausea but wish to continue.", "source": { "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/210557s000lbl.pdf", "title": "VYLEESI (bremelanotide) injection — Highlights of Prescribing Information, original approval", "publisher": "FDA", "date": "2019-06-21", "quote": "In the phase 3 placebo-controlled trials, nausea was the most commonly reported adverse reaction, reported in 40% of VYLEESI-treated patients, requiring anti-emetic therapy in 13% of VYLEESI-treated patients and leading to premature discontinuation from the trials for 8% of VYLEESI-treated patients." }, "verifiedAt": "2026-07-16" }, { "signal": "A Phase 4 study reported that pre-treatment with oral ondansetron did not reduce the incidence of nausea associated with VYLEESI, and the current label states such pre-treatment is not recommended.", "note": "This finding is cited to the CURRENT SPL, not to the 2019 approval label: the Phase 4 study postdates the 2019 label, and the word 'ondansetron' does not appear anywhere in that document (checked by extracting all 19 pages on 2026-07-16). We do not characterise the study as a postmarketing requirement or commitment — the approval letter's only 505(o) requirements are two pregnancy registry studies, and it never mentions ondansetron. Who asked for the study is not something we can source, so we do not say. The intuitive workaround was tested and failed. Note the distinction the label preserves and that summaries tend to flatten: what is not recommended is ondansetron PRE-treatment. The label states separately that treatment with ondansetron after VYLEESI administration, or after the onset of nausea, has not been formally studied — that is an absence of evidence, not a finding either way.", "source": { "url": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=f1d0c1b5-2f39-4bad-a6a4-0066e3ad5dcf", "title": "VYLEESI (bremelanotide) injection, solution — Prescribing Information (current SPL)", "publisher": "DailyMed (U.S. National Library of Medicine)", "date": "2025-11-13", "quote": "In a phase 4, single-dose, placebo-controlled clinical study, pre-treatment with oral ondansetron (a 5-HT3 receptor antagonist) did not reduce the incidence of nausea associated with VYLEESI treatment. In this study, 228 healthy women were randomized (1:1) … Therefore, pre-treatment with oral ondansetron … does not reduce the incidence of VYLEESI-associated nausea and is not recommended." }, "verifiedAt": "2026-07-16" }, { "signal": "Focal hyperpigmentation — including of the face, gingiva and breasts — was reported in 1% of Phase 3 patients receiving up to eight doses per month, versus no placebo patients. In a separate study, 38% developed focal hyperpigmentation after daily use for eight days.", "note": "The frequency gradient is the point, and it is the signal most likely to be understated for grey-market users. At the labeled intermittent frequency the rate is 1%; with daily use it was 38%, with a further 14% developing new pigmentary changes on continued daily use. FDA states that patients with dark skin were more likely to develop it and that resolution after stopping was not confirmed in all patients — meaning a potentially permanent cosmetic effect. This is mechanistically expected from MC1R agonism (see moleculeNote), not a surprise, and anyone using the compound more frequently than the label contemplates is sitting on the wrong end of that gradient.", "source": { "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/210557s000lbl.pdf", "title": "VYLEESI (bremelanotide) injection — Highlights of Prescribing Information, original approval", "publisher": "FDA", "date": "2019-06-21", "quote": "Resolution of the focal hyperpigmentation was not confirmed in all patients after discontinuation of VYLEESI." }, "verifiedAt": "2026-07-16" }, { "signal": "VYLEESI transiently increases blood pressure and reduces heart rate after each dose, and is CONTRAINDICATED in patients with uncontrolled hypertension or known cardiovascular disease.", "note": "Reported maximal increases were 6 mmHg systolic and 3 mmHg diastolic, peaking 2-4 hours post-dose with a corresponding heart-rate reduction of up to 5 bpm, usually resolving within 12 hours. The magnitude is modest; the contraindication is not conditional. The label also states VYLEESI is not recommended in patients at high risk for cardiovascular disease. A contraindication presupposes a prescriber who screened for it — that screening step is precisely what is absent when the compound is bought as a research chemical, which makes this the signal that translates worst to grey-market use.", "source": { "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/210557s000lbl.pdf", "title": "VYLEESI (bremelanotide) injection — Highlights of Prescribing Information, original approval", "publisher": "FDA", "date": "2019-06-21", "quote": "VYLEESI is contraindicated in patients who have uncontrolled hypertension or known cardiovascular disease." }, "verifiedAt": "2026-07-16" }, { "signal": "One patient in the Phase 3 trials experienced a serious headache event: intractable pain leading to hospitalization.", "note": "Headache occurred in 11% of VYLEESI patients versus 2% on placebo. Serious adverse reactions overall were reported in 1.1% of VYLEESI-treated patients versus 0.5% on placebo.", "source": { "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/210557s000lbl.pdf", "title": "VYLEESI (bremelanotide) injection — Highlights of Prescribing Information, original approval", "publisher": "FDA", "date": "2019-06-21" }, "verifiedAt": "2026-07-16" } ], "faqs": [ { "question": "Is PT-141 FDA-approved?", "answer": "Yes, but not for what it is sold for. PT-141 (bremelanotide) is approved by FDA as VYLEESI under NDA 210557, approved 21 June 2019, and only for the treatment of premenopausal women with acquired, generalized hypoactive sexual desire disorder (HSDD). The approved label's Limitations of Use state: 'VYLEESI is not indicated for the treatment of HSDD in postmenopausal women or in men. VYLEESI is not indicated to enhance sexual performance.' That wording has been on the label since the day of approval and is identical in the current prescribing information effective 13 November 2025. A seller invoking 'FDA-approved' to a male customer, or for sexual performance, is invoking an approval whose own text excludes that customer and that use.", "source": { "url": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=f1d0c1b5-2f39-4bad-a6a4-0066e3ad5dcf", "title": "VYLEESI (bremelanotide) injection, solution — Prescribing Information (current SPL)", "publisher": "DailyMed (U.S. National Library of Medicine)", "date": "2025-11-13", "quote": "Limitations of Use: VYLEESI is not indicated for the treatment of HSDD in postmenopausal women or in men. VYLEESI is not indicated to enhance sexual performance." }, "verifiedAt": "2026-07-16" }, { "question": "Does PT-141 work for men?", "answer": "FDA has not approved PT-141 (bremelanotide) for use in men, and the approved VYLEESI label states explicitly that it 'is not indicated for the treatment of HSDD in postmenopausal women or in men' and 'is not indicated to enhance sexual performance'. The only population in which FDA has found bremelanotide's efficacy established is premenopausal women with acquired, generalized hypoactive sexual desire disorder; the label separately states that safety and effectiveness have not been established in pediatric or in geriatric patients. Both pivotal Phase 3 trials enrolled premenopausal women only. The absence of an approved male indication is not evidence that the compound works in men and awaits paperwork — it means no such use has been demonstrated to FDA.", "source": { "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/210557s000lbl.pdf", "title": "VYLEESI (bremelanotide) injection — Highlights of Prescribing Information, original approval", "publisher": "FDA", "date": "2019-06-21", "quote": "VYLEESI is not for the treatment of HSDD in women who have gone through menopause or in men." }, "verifiedAt": "2026-07-16" }, { "question": "Is there any human evidence that PT-141 works?", "answer": "Yes — and it is real, narrow, and smaller than the marketing implies. FDA approved PT-141 (bremelanotide) on what its label describes as 'two identical, Phase 3, randomized, double-blind, placebo-controlled trials: NCT02333071 and NCT02338960', in premenopausal women with acquired, generalized hypoactive sexual desire disorder, in which the compound was actually administered by subcutaneous injection rather than merely measured. On FDA's own reported results, the co-primary FSFI-Desire score (scale 1.2 to 6.0) improved by a mean of 0.5 versus 0.2 for placebo in Study 1 and 0.6 versus 0.2 in Study 2 — a placebo-subtracted difference of roughly 0.3 to 0.4 points on a 4.8-point questionnaire, statistically significant and small. FDA also reports that there was no significant difference between VYLEESI and placebo in the number of satisfying sexual events, a secondary endpoint. The demonstrated effect is on self-rated desire and distress, not on how much satisfying sex participants had.", "source": { "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/210557s000lbl.pdf", "title": "VYLEESI (bremelanotide) injection — Highlights of Prescribing Information, original approval", "publisher": "FDA", "date": "2019-06-21", "quote": "There was no significant difference between treatment groups in the change from baseline to end of study visit in the number of satisfying sexual events (SSEs), a secondary endpoint." }, "verifiedAt": "2026-07-16" }, { "question": "Is PT-141 safe?", "answer": "PT-141 (bremelanotide) has documented harms serious enough that FDA contraindicates it outright in some patients: the approved VYLEESI label states it 'is contraindicated in patients who have uncontrolled hypertension or known cardiovascular disease', because each dose transiently raises blood pressure and lowers heart rate. In the Phase 3 trials FDA reports nausea in 40% of VYLEESI-treated patients versus 1% on placebo, requiring anti-emetic therapy in 13% and causing 8% to stop; 18% discontinued for adverse reactions overall versus 2% on placebo. Focal hyperpigmentation — including of the face, gingiva and breasts — occurred in 1% at the label's intermittent frequency but in 38% of subjects in a study using the drug daily for eight days, and FDA states that 'Resolution of the focal hyperpigmentation was not confirmed in all patients after discontinuation of VYLEESI', meaning the skin change may be permanent. A contraindication only protects a patient whose prescriber screened for it, which nobody does when the compound is bought as a research chemical.", "source": { "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/210557s000lbl.pdf", "title": "VYLEESI (bremelanotide) injection — Highlights of Prescribing Information, original approval", "publisher": "FDA", "date": "2019-06-21", "quote": "VYLEESI is contraindicated in patients who have uncontrolled hypertension or known cardiovascular disease." }, "verifiedAt": "2026-07-16" }, { "question": "Is PT-141 legal in 2026?", "answer": "PT-141 (bremelanotide) is lawful in the United States in exactly one form: VYLEESI, a prescription drug approved under NDA 210557, which Drugs@FDA shows as of 16 July 2026 with sponsor Cosette and marketing status 'Prescription' — the query returns one application and no generic. Being an approved prescription drug is not the same as being generally legal to sell or buy. The approval attaches to that specific product, made by that manufacturer, dispensed by a pharmacy against a prescription. 'FDA-approved' is a fact about VYLEESI; it is not a fact about bremelanotide powder sold as a research chemical, which is a different product with no approval of its own, and it says nothing about whether a given sale of one is lawful.", "source": { "url": "https://api.fda.gov/drug/drugsfda.json?search=openfda.generic_name:\"bremelanotide\"+OR+products.active_ingredients.name:\"BREMELANOTIDE+ACETATE\"&limit=5", "title": "Drugs@FDA — approved drug products database, queried for bremelanotide (openFDA)", "publisher": "FDA", "date": "2026-07-16", "quote": "\"application_number\": \"NDA210557\", \"sponsor_name\": \"COSETTE\" … \"marketing_status\": \"Prescription\"" }, "verifiedAt": "2026-07-16" }, { "question": "Is bremelanotide on FDA's 503A bulk drug substances list?", "answer": "No. Bremelanotide appears in no category — 1, 2 or 3 — of FDA's 503A bulk drug substances list, updated 14 May 2026 and text-extracted directly on 16 July 2026. For bremelanotide that absence means something different from what it means for the unapproved peptides on this site, and reading it the same way would be mechanically consistent and completely wrong. The 503A nomination pathway exists for bulk substances that are NOT components of FDA-approved drugs; bremelanotide is the active ingredient of an approved drug, so that pathway was never the relevant one for it. Absence here is not withdrawal, not rejection, and not a safety finding. This record does not adjudicate whether bremelanotide may lawfully be compounded — that turns on other 503A conditions, including the restriction on compounding drugs that are essentially copies of a commercially available approved product, which we have not verified and therefore do not assert.", "source": { "url": "https://www.fda.gov/media/94155/download", "title": "Bulk Drug Substances Nominated for Use in Compounding Under Section 503A of the Federal Food, Drug, and Cosmetic Act", "publisher": "FDA", "date": "2026-05-14" }, "verifiedAt": "2026-07-16" } ] }, { "slug": "retatrutide", "name": "Retatrutide", "aliases": [ "LY3437943", "Triple G", "GGG tri-agonist" ], "url": "https://peptides101.com/compounds/retatrutide", "moleculeNote": "A single synthetic peptide that agonises three receptors — glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1), and glucagon — described as such in the Phase 2 report (NEJM 2023) and the Phase 3 report (Lancet 2026). Unlike BPC-157 or TB-500, there is no fragment-versus-full-length ambiguity in the literature: 'retatrutide' and 'LY3437943' denote one investigational Eli Lilly molecule. The ambiguity is elsewhere — nothing verifies that a vial sold as 'retatrutide' by a research-chemical vendor contains that molecule, at that purity, at any stated content. It is not a component of any FDA-approved drug product, so no vial of it comes from an approved supply (recorded, sourced, under FDA findings).", "quickAnswer": "Retatrutide (LY3437943) is not approved by FDA for any indication, and FDA states it 'cannot be used in compounding under federal law' — it appears on neither the 503A Bulks List, the 503B Bulks List, nor FDA's drug shortage list, leaving no lawful US route to a compounded retatrutide product, and FDA has issued warning letters treating retatrutide sold online as an unapproved new drug. Its human evidence is nonetheless genuine: in the Phase 3 TRANSCEND-T2D-1 trial published in The Lancet in June 2026, investigators randomised 537 adults with type 2 diabetes to weekly subcutaneous retatrutide or placebo and reported substantially greater HbA1c reduction at week 40 in the retatrutide groups — but those trials used Eli Lilly's investigational material, FDA says retatrutide has 'not been found safe and effective for any condition', and FDA warns that products sold as retatrutide direct to consumers are of unknown quality and may be harmful.", "fdaStatus": { "value": "investigational", "note": "In active clinical development with an identifiable sponsor and registered trials. Not approved. Being in trials is not evidence that it works.", "source": { "url": "https://www.pharmacy.ohio.gov/documents/pubs/special/compounding/fda%20letter%20-%20retatrutide%20in%20compounded%20drug%20products.pdf", "title": "Letter to the National Association of Boards of Pharmacy re: Compounded Drug Products Containing Retatrutide", "publisher": "FDA", "date": "2025-03-31", "quote": "Retatrutide is not the subject of an applicable USP or NF monograph, is not a component of an FDA-approved drug product, and does not appear on the 503A Bulks List." }, "verifiedAt": "2026-07-16" }, "compoundingStatus": { "value": "never-nominated", "note": "Absent from Categories 1, 2 and 3 of the bulks list updated 2026-05-14 — verified by fetching and text-extracting the document directly; the string 'retatrutide' does not occur in it. Recorded as never-nominated rather than withdrawn-from-nomination: FDA's 2025 letter walks through each of the three statutory 503A prongs and reports that retatrutide satisfies none, without referencing any nomination, category placement or withdrawal — which a letter written specifically to explain its 503A status would have had occasion to mention. First-in-human dosing was 2019 (NCT03841630), well after the nomination window that produced the Category 1/2/3 cohort. HONEST LIMIT: absence from the categories is equally consistent with withdrawal (BPC-157 is also absent), so this rests on the letter's silence plus chronology, not on a document stating 'never nominated'. If a nomination record surfaces, this field changes. 'Never nominated' IS NOT A LOOPHOLE AND IS NOT PERMISSION — it is the opposite. The withdrawn peptides at least have a nomination history; retatrutide has no lawful compounding pathway under either 503A or 503B, which FDA states in terms.", "source": { "url": "https://www.pharmacy.ohio.gov/documents/pubs/special/compounding/fda%20letter%20-%20retatrutide%20in%20compounded%20drug%20products.pdf", "title": "Letter to the National Association of Boards of Pharmacy re: Compounded Drug Products Containing Retatrutide", "publisher": "FDA", "date": "2025-03-31", "quote": "Retatrutide is not the subject of an applicable USP or NF monograph, is not a component of an FDA-approved drug product, and does not appear on the 503A Bulks List." }, "verifiedAt": "2026-07-16" }, "evidence": { "tier": "proven-in-humans", "humanAdministrationChecked": true, "note": "ADMINISTRATION CHECK PASSED, EXPLICITLY. Retatrutide is a synthetic investigational drug, not an endogenous peptide, so the biomarker trap that empties MOTS-c's and TB-500's apparent trial counts does not apply here — but the check was run per-study anyway rather than assumed. In TRANSCEND-T2D-1 (NCT06354660), a 40-week Phase 3 double-blind placebo-controlled trial at 48 sites in the USA, Mexico and India, investigators randomised 537 adults with type 2 diabetes to subcutaneous retatrutide or placebo weekly; they reported substantially greater reduction in HbA1c at week 40 in every retatrutide group than with placebo. In the earlier Phase 2 obesity trial (NCT04881760, NEJM 2023), investigators randomised 338 adults and reported substantially greater weight reduction at 48 weeks in the highest retatrutide group than with placebo. The per-arm figures are left to the cited papers deliberately: an amount beside a frequency reconstructs a regimen, and this record does not publish one. Both trials administered the drug; both were funded by Eli Lilly; the ClinicalTrials.gov intervention record for each reads 'Administered SC'. WHAT THE TIER DOES AND DOES NOT MEAN. It means: efficacy on the endpoints those trials measured — glycaemic control and body weight — is established by adequate, well-controlled human trials. It does NOT mean approved, and it does not mean safe: FDA's own position is that retatrutide has 'not been found safe and effective for any condition' (recorded under FDA findings). It does not mean the outcomes that matter longest are known — the cardiovascular and kidney outcomes trial (NCT06383390, n=10,000, Eli Lilly, Phase 3) began 2024-04-30, is active and not recruiting, has posted no results, and runs about five years. Most of the Phase 3 programme is likewise unreported: of 14 Eli Lilly Phase 3 registrations confirmed on ClinicalTrials.gov on 2026-07-16, none has results posted there, and exactly one (TRANSCEND-T2D-1) is peer-reviewed and published. Other Phase 3 outcomes exist so far only as company press releases, which are not a primary evidentiary source and are not cited here. And none of it transfers to grey-market product: these findings describe Lilly's investigational material under trial conditions, not a vial bought from a vendor.", "source": { "url": "https://pubmed.ncbi.nlm.nih.gov/42250575/", "title": "Efficacy and safety of retatrutide, a GIP, GLP-1, and glucagon receptor agonist, in people with type 2 diabetes and inadequate glycaemic control with diet and exercise (TRANSCEND-T2D-1): a double-blind, randomised, phase 3 trial", "publisher": "The Lancet", "date": "2026-06-13", "quote": "Participants were randomly assigned (1:1:1:1) to receive retatrutide […] or placebo by once-weekly subcutaneous injection." }, "verifiedAt": "2026-07-16" }, "fdaApproval": null, "fdaFindings": [ { "finding": "FDA states that retatrutide cannot be used in compounding under federal law, and that it has not been found safe and effective for any condition.", "note": "Read this against the evidence tier rather than instead of it. Both are true and they are not in conflict: a published Phase 3 trial can establish efficacy on its endpoints while FDA — which has not reviewed a marketing application, because none has been approved — has made no safety-and-effectiveness finding. 'Not found safe and effective' is a statement about the approval process, not a finding that the trials failed. The vendor corpus quotes the trial results without this sentence; the cautious corpus quotes this sentence as though it meant the drug does not work. Both are misreadings.", "source": { "url": "https://www.fda.gov/drugs/postmarket-drug-safety-information-patients-and-providers/fdas-concerns-unapproved-glp-1-drugs-used-weight-loss", "title": "FDA's Concerns with Unapproved GLP-1 Drugs Used for Weight Loss", "publisher": "FDA", "date": "2026-06-15", "quote": "Retatrutide and cagrilintide cannot be used in compounding under federal law. Additionally, these are not components of FDA-approved drugs and have not been found safe and effective for any condition." }, "verifiedAt": "2026-07-16" }, { "finding": "FDA finds retatrutide satisfies none of the three statutory conditions for a bulk drug substance under 503A, and does not appear on the 503B Bulks List or FDA's drug shortage list.", "note": "The shortage-list point is what closes the door that semaglutide and tirzepatide briefly left open. Compounders could supply those during declared shortages; retatrutide has never been on the shortage list because it has never been marketed, so that route never existed for it. FDA sent this letter to NABP, the Federation of State Medical Boards and the National Council of State Boards of Nursing — it is addressed to prescribers and dispensers, not only to compounders.", "source": { "url": "https://www.pharmacy.ohio.gov/documents/pubs/special/compounding/fda%20letter%20-%20retatrutide%20in%20compounded%20drug%20products.pdf", "title": "Letter to the National Association of Boards of Pharmacy re: Compounded Drug Products Containing Retatrutide", "publisher": "FDA", "date": "2025-03-31", "quote": "Retatrutide does not appear on the 503B Bulks List, nor does it appear on FDA's drug shortage list. Therefore, compounded retatrutide products would not at this time qualify for the exemptions under section 503B of the FD&C Act." }, "verifiedAt": "2026-07-16" }, { "finding": "FDA has warned telehealth companies for marketing unapproved retatrutide directly to consumers, API distributors for selling it to compounders, and outsourcing facilities for repackaging it.", "note": "Enforcement here reaches the whole chain, not just the manufacturer — prescriber-facing telehealth included. Consistent with the Watkins indictment (D. Utah, 1:26-cr-00015, 2026-04-01), which charges misbranding under 352(b): sourcing and labeling are the line, and a compound's category status — or absence from every category, as here — is neither the safety line nor the criminal line. The quote is FDA's own three-item list, reproduced in full; the run-on reads oddly because the source renders it as a lead-in and three bullets, and flattening it was preferred to silently rewriting FDA's words.", "source": { "url": "https://www.fda.gov/drugs/postmarket-drug-safety-information-patients-and-providers/fdas-concerns-unapproved-glp-1-drugs-used-weight-loss", "title": "FDA's Concerns with Unapproved GLP-1 Drugs Used for Weight Loss", "publisher": "FDA", "date": "2026-06-15", "quote": "The agency has warned: Telehealth companies for marketing unapproved drugs such as retatrutide, including instances of direct marketing to consumers. Active pharmaceutical ingredient distributors for selling retatrutide and other GLP-1 drugs to compounders. Outsourcing facilities for repackaging retatrutide." }, "verifiedAt": "2026-07-16" }, { "finding": "In a warning letter to a retatrutide seller, FDA found the products to be unapproved new drugs and held that 'Research Use Only' labeling did not defeat evidence of intended use.", "note": "This is the sentence that answers the question the market actually asks about retatrutide — not 'is the molecule legit' but 'does the research-use-only label make the sale lawful'. FDA's answer, in this letter and consistently across the 2026-03-31 tranche, is that intended use is established from the seller's own website copy, and a disclaimer contradicted by that copy is not a defence. FDA also recorded a general finding about the dosage form rather than the molecule: 'injectable drug products can pose risks of serious harm to users… bypass some of the body's key defenses against toxins and microorganisms'. WHAT THIS IS NOT: not a finding about retatrutide's pharmacology, and not a finding that the Lilly trials are wrong. It is a finding about a seller. The letter concerns Gram Peptides specifically; it is cited here as evidence of FDA's legal position on retatrutide sold this way, not as a claim about any other vendor.", "source": { "url": "https://www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/warning-letters/gram-peptides-721806-03312026", "title": "Warning Letter — Gram Peptides (MARCS-CMS 721806)", "publisher": "FDA", "date": "2026-03-31", "quote": "Despite statements on your product labeling marketing your products for “Research Use Only,” and “not intended for human consumption, medical use, or veterinary use,” evidence obtained from your website establishes that your products are intended to be drugs for human use." }, "verifiedAt": "2026-07-16" }, { "finding": "FDA has established a green list import alert (66-80) directed at GLP-1 active pharmaceutical ingredients with potential quality concerns entering the US supply chain.", "note": "Included because it is the concrete mechanism behind the abstract 'unknown quality' warning: FDA is stopping material at the border, which tells you where it judges the risk to sit. Read the scope precisely, in both directions. The alert is aimed at GLP-1 APIs broadly, not at retatrutide by name, so it is recorded as context for the supply chain retatrutide arrives through rather than as a retatrutide-specific action. And FDA states its own limits: the alert 'does not apply to GLP-1 API from manufacturers that … appear to be in compliance', and 'does not stop the legal importation into the U.S. market of GLP-1 APIs from compliant API manufacturers, nor does it create any new limits on the legal compounding of GLP-1 drugs'. That last clause does nothing for retatrutide, which has no lawful compounding to limit.", "source": { "url": "https://www.fda.gov/drugs/postmarket-drug-safety-information-patients-and-providers/fdas-concerns-unapproved-glp-1-drugs-used-weight-loss", "title": "FDA's Concerns with Unapproved GLP-1 Drugs Used for Weight Loss", "publisher": "FDA", "date": "2026-06-15", "quote": "The agency has established a green list import alert (66-80) to help stop GLP-1 active pharmaceutical ingredients (APIs) that have potential quality concerns from entering the U.S. supply chain." }, "verifiedAt": "2026-07-16" } ], "safetySignals": [ { "signal": "FDA has warned companies illegally selling unapproved retatrutide falsely labeled 'for research purposes' or 'not for human consumption', sold direct to consumers with dosing instructions, and recommends consumers not purchase them, as they are of unknown quality and may be harmful.", "note": "This is the safety signal that actually applies to the way people obtain retatrutide. It is not a signal about the molecule — it is a signal about the supply. Note what is NOT claimed here. FDA's GLP-1 page does spell out failure modes for illegally sold product — wrong or harmful ingredients, 'too little, too much or no active ingredient at all' — but that language sits in its counterfeit-Ozempic section and in a bullet list whose lead sentence scopes it to 'illegally marketed semaglutide and tirzepatide'. The section that names retatrutide says 'unknown quality and may be harmful' and stops there, so that is where this record stops too; importing the more specific failure modes would attribute to retatrutide what FDA wrote about other drugs. The trial evidence cannot speak to any of it either way, because the trials used Lilly's material.", "source": { "url": "https://www.pharmacy.ohio.gov/documents/pubs/special/compounding/fda%20letter%20-%20retatrutide%20in%20compounded%20drug%20products.pdf", "title": "Letter to the National Association of Boards of Pharmacy re: Compounded Drug Products Containing Retatrutide", "publisher": "FDA", "date": "2025-03-31", "quote": "Additionally, FDA has warned companies that have illegally sold unapproved drugs containing retatrutide and other ingredients that are falsely labeled “for research purposes” or “not for human consumption.” These products have been sold directly to consumers for human use with dosing instructions. The agency recommends that consumers not purchase these products which are of unknown quality and may be harmful to their health and encourages health care providers to discuss this issue with their patients." }, "verifiedAt": "2026-07-16" }, { "signal": "In the Phase 2 obesity trial (n=338), investigators reported that the most common adverse events with retatrutide were gastrointestinal, dose-related and mostly mild to moderate, and that dose-dependent increases in heart rate peaked at 24 weeks and declined thereafter.", "note": "Attributed to the trial, and scoped to it. The most frequently reported adverse events in the ClinicalTrials.gov results posting for NCT04881760 were nausea (91 participants affected), decreased appetite (62), diarrhoea (45), vomiting (34) and constipation (32). Two limitations bound this: 338 participants over 48 weeks cannot characterise uncommon or long-latency harms, and the heart-rate finding was observed under monitored titration with a controlled starting dose — a condition that does not exist outside a trial. The Phase 3 report (Lancet 2026) characterised the profile as 'consistent with molecules with GLP-1 agonist activity'.", "source": { "url": "https://pubmed.ncbi.nlm.nih.gov/37366315/", "title": "Triple-Hormone-Receptor Agonist Retatrutide for Obesity — A Phase 2 Trial", "publisher": "The New England Journal of Medicine", "date": "2023-08-10", "quote": "The most common adverse events in the retatrutide groups were gastrointestinal; these events were dose-related, were mostly mild to moderate in severity, and were partially mitigated with a lower starting dose […]. Dose-dependent increases in heart rate peaked at 24 weeks and declined thereafter." }, "verifiedAt": "2026-07-16" }, { "signal": "A Phase 2 registration for retatrutide (NCT07467447) is sponsored by Hudson Biotech and carries an official title identical, word for word, to Eli Lilly's genuine Phase 2 trial NCT04881760.", "note": "Recorded as a safety signal because registry contamination is a hazard to the reader, not a curiosity. ClinicalTrials.gov is self-reported and unvetted: registration is not vetting, and 'RECRUITING' is a sponsor's assertion. NCT07467447 matches the known contaminated cluster on every marker — sponsor Hudson Biotech, which sells research peptides; a single site; start date 2026-02-15; status recruiting; zero results — and its official title is a verbatim clone of Lilly's, exactly as NCT07481747 clones Lilly's SURMOUNT-1. It is not cited as evidence anywhere in this record and should not be mistaken for the real NCT04881760, whose results are posted and published in NEJM. Verified 2026-07-16 against the ClinicalTrials.gov API. Related registrations in the same cluster are self-marked: NCT07481734 carries '(Mock Study)' in its official title and NCT07487363 states in its own brief summary that it is fictional — and vendor sites are already laundering that one as '2026 human trial data'.", "source": { "url": "https://clinicaltrials.gov/study/NCT07467447", "title": "A Phase 2 Study of Once-Weekly LY3437943 Compared With Placebo in Participants Who Have Obesity or Are Overweight With Weight-Related Comorbidities", "publisher": "ClinicalTrials.gov", "date": "2026-02-15" }, "verifiedAt": "2026-07-16" } ], "faqs": [ { "question": "Is retatrutide legal in 2026?", "answer": "No — there is no lawful way to obtain retatrutide in the United States outside a clinical trial. FDA wrote to the National Association of Boards of Pharmacy on 31 March 2025 that retatrutide is not the subject of a USP or NF monograph, is not a component of an FDA-approved drug product, and does not appear on the 503A Bulks List — so it satisfies none of the three statutory conditions for a bulk drug substance, and compounded retatrutide products 'would not at this time qualify for the exemptions under section 503A of the FD&C Act'. FDA found the same for section 503B — retatrutide appears on neither the 503B Bulks List nor FDA's drug shortage list. NABP circulated the letter to state boards of pharmacy with the summary that compounding with retatrutide 'is prohibited by all pharmacies compounding under either Section 503A or 503B'.", "source": { "url": "https://www.pharmacy.ohio.gov/documents/pubs/special/compounding/fda%20letter%20-%20retatrutide%20in%20compounded%20drug%20products.pdf", "title": "Letter to the National Association of Boards of Pharmacy re: Compounded Drug Products Containing Retatrutide", "publisher": "FDA", "date": "2025-03-31", "quote": "Retatrutide is not the subject of an applicable USP or NF monograph, is not a component of an FDA-approved drug product, and does not appear on the 503A Bulks List. Therefore, compounded retatrutide products would not at this time qualify for the exemptions under section 503A of the FD&C Act." }, "verifiedAt": "2026-07-16" }, { "question": "Did FDA approve retatrutide?", "answer": "No. Retatrutide is not approved by FDA for any indication, in any population, by any route, and as of 15 June 2026 FDA states that retatrutide and cagrilintide 'are not components of FDA-approved drugs and have not been found safe and effective for any condition'. Retatrutide is an investigational Eli Lilly molecule still in Phase 3 development. Note precisely what FDA's phrase means: 'not been found safe and effective' describes the absence of an approval decision, because no marketing application for retatrutide has been approved — it is not a finding that the clinical trials failed.", "source": { "url": "https://www.fda.gov/drugs/postmarket-drug-safety-information-patients-and-providers/fdas-concerns-unapproved-glp-1-drugs-used-weight-loss", "title": "FDA's Concerns with Unapproved GLP-1 Drugs Used for Weight Loss", "publisher": "FDA", "date": "2026-06-15", "quote": "Retatrutide and cagrilintide cannot be used in compounding under federal law. Additionally, these are not components of FDA-approved drugs and have not been found safe and effective for any condition." }, "verifiedAt": "2026-07-16" }, { "question": "Can I get retatrutide from a compounding pharmacy?", "answer": "No. FDA has stated in a letter to the National Association of Boards of Pharmacy, and again on its own website, that retatrutide cannot lawfully be used in compounding under either section 503A or section 503B of the Federal Food, Drug, and Cosmetic Act. Retatrutide does not appear on the 503B Bulks List, and — unlike semaglutide and tirzepatide, which compounders could supply during declared shortages — it has never appeared on FDA's drug shortage list, because it has never been marketed. FDA has warned outsourcing facilities for repackaging retatrutide and API distributors for selling it to compounders. A pharmacy or telehealth service offering compounded retatrutide is not operating in a grey area FDA has yet to address; it is doing something FDA has addressed twice, in writing, by name.", "source": { "url": "https://www.pharmacy.ohio.gov/documents/pubs/special/compounding/fda%20letter%20-%20retatrutide%20in%20compounded%20drug%20products.pdf", "title": "Letter to the National Association of Boards of Pharmacy re: Compounded Drug Products Containing Retatrutide", "publisher": "FDA", "date": "2025-03-31", "quote": "Retatrutide does not appear on the 503B Bulks List, nor does it appear on FDA's drug shortage list. Therefore, compounded retatrutide products would not at this time qualify for the exemptions under section 503B of the FD&C Act." }, "verifiedAt": "2026-07-16" }, { "question": "Is there any human evidence that retatrutide works?", "answer": "Yes — retatrutide is one of the few compounds sold on the peptide market with a published, peer-reviewed Phase 3 randomised trial. In TRANSCEND-T2D-1 (NCT06354660), a 40-week double-blind trial at 48 sites in the USA, Mexico and India reported in The Lancet on 13 June 2026, investigators randomised 537 adults with type 2 diabetes to weekly subcutaneous retatrutide or placebo and reported substantially greater reduction in HbA1c at week 40 in every retatrutide group than with placebo. Earlier, in a Phase 2 obesity trial reported in the New England Journal of Medicine in 2023, investigators randomised 338 adults and reported substantially greater weight reduction at 48 weeks in the highest retatrutide group than with placebo. Both trials were funded by Eli Lilly and used Lilly's investigational material. That evidence describes the molecule under trial conditions and says nothing about the contents, purity or identity of a vial sold as 'retatrutide' by a research-chemical vendor.", "source": { "url": "https://pubmed.ncbi.nlm.nih.gov/42250575/", "title": "Efficacy and safety of retatrutide, a GIP, GLP-1, and glucagon receptor agonist, in people with type 2 diabetes and inadequate glycaemic control with diet and exercise (TRANSCEND-T2D-1): a double-blind, randomised, phase 3 trial", "publisher": "The Lancet", "date": "2026-06-13", "quote": "Participants were randomly assigned (1:1:1:1) to receive retatrutide […] or placebo by once-weekly subcutaneous injection." }, "verifiedAt": "2026-07-16" }, { "question": "Is retatrutide sold 'for research purposes only' legal to buy?", "answer": "No. FDA has held that a 'research use only' or 'not for human consumption' label does not make selling retatrutide lawful, because intended use is established from the seller's own marketing rather than its disclaimer. In a warning letter of 31 March 2026 to Gram Peptides, FDA found that despite labeling the products 'Research Use Only' and 'not intended for human consumption', evidence from the firm's website established the products were 'intended to be drugs for human use' — making them unapproved new drugs whose introduction into interstate commerce violates sections 301(d) and 505(a) of the Federal Food, Drug, and Cosmetic Act. FDA added that these products are especially concerning because injectable drug products 'bypass some of the body's key defenses against toxins and microorganisms'.", "source": { "url": "https://www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/warning-letters/gram-peptides-721806-03312026", "title": "Warning Letter — Gram Peptides (MARCS-CMS 721806)", "publisher": "FDA", "date": "2026-03-31", "quote": "Based on our review, these products are unapproved new drugs under section 505(a) of the Federal Food, Drug, and Cosmetic Act (FD&C Act), 21 U.S.C. 355(a). As explained further below, introducing or delivering these products for introduction into interstate commerce violates sections 301(d) and 505(a) of the FD&C Act, 21 U.S.C. 331(d) and 355(a)." }, "verifiedAt": "2026-07-16" } ] }, { "slug": "selank", "name": "Selank", "aliases": [ "Selank acetate", "TP-7", "Thr-Lys-Pro-Arg-Pro-Gly-Pro" ], "url": "https://peptides101.com/compounds/selank", "moleculeNote": "A synthetic heptapeptide: the tuftsin fragment Thr-Lys-Pro-Arg extended with the stabilising tripeptide Pro-Gly-Pro. FDA's withdrawn-nomination entry names the salt specifically — 'Selank acetate (TP-7)' — not the free base. Distinct from semax, which is an unrelated ACTH(4-7) analogue; the two are frequently sold as a combined product and are frequently conflated, including in their regulatory posture.", "quickAnswer": "Selank is not on FDA's 503A bulks list and cannot lawfully be compounded from bulk: FDA lists 'Selank acetate (TP-7)' among bulk drug substances previously in Category 2 whose nominations were withdrawn by the nominators, which moved its status sideways rather than toward legality. Selank has genuinely been administered to humans — three small Russian trials, none placebo-controlled and none replicated outside Russia — but FDA states it lacks important information regarding any safety issues raised by selank acetate administered to humans.", "fdaStatus": { "value": "not-approved", "note": "Not an FDA-approved drug for any indication, and not in active development toward approval. That says nothing about whether it is sold — it is.", "source": { "url": "https://www.fda.gov/drugs/human-drug-compounding/certain-bulk-drug-substances-use-compounding-may-present-significant-safety-risks", "title": "Certain Bulk Drug Substances for Use in Compounding May Present Significant Safety Risks", "publisher": "FDA", "date": "2026-04-22", "quote": "This list of bulk drug substances previously in category 2 of the interim policies were withdrawn by the nominators." }, "verifiedAt": "2026-07-16" }, "compoundingStatus": { "value": "withdrawn-from-nomination", "note": "Absent from Categories 1, 2 and 3 of the bulks list updated 2026-05-14 — verified by fetching and text-extracting the document directly. Category 2 now contains exactly six substances, one of which is a peptide (kisspeptin-10). Absence alone does not distinguish 'withdrawn' from 'never nominated', so this status is taken from FDA's own nominated-but-withdrawn table, which lists 'Selank acetate (TP-7)' explicitly. It left Category 2 because the nominators withdrew the nominations — not because it moved toward legality. It did not enter Category 1, it is not on the 503A bulks list, and it remains non-compoundable. Note also that withdrawal is not the criminal line: the Watkins indictment (D. Utah, 1:26-cr-00015, 2026-04-01) charges misbranding under 352(b), which is why Category 1 substances sit in the same indictment as withdrawn ones.", "source": { "url": "https://www.fda.gov/drugs/human-drug-compounding/certain-bulk-drug-substances-use-compounding-may-present-significant-safety-risks", "title": "Certain Bulk Drug Substances for Use in Compounding May Present Significant Safety Risks", "publisher": "FDA", "date": "2026-04-22", "quote": "This list of bulk drug substances previously in category 2 of the interim policies were withdrawn by the nominators." }, "verifiedAt": "2026-07-16" }, "evidence": { "tier": "promising-but-unproven", "humanAdministrationChecked": true, "note": "Administration check RUN AND PASSED, which is why this tier is not 'animal-or-in-vitro-only'. Each indexed human trial was opened and confirmed to ADMINISTER selank to patients rather than measure an endogenous peptide as a biomarker — the failure mode that reduces MOTS-c's apparent four human RCTs and TB-500's one to a real count of zero. Selank's human data is real. Three trials are indexed in PubMed, all Russian-language, all in Zh Nevrol Psikhiatr Im S S Korsakova: Zozulia et al. 2008 (PMID 18454096, n=62, selank 30 vs medazepam 32, generalized anxiety disorder and neurasthenia); Medvedev et al. 2014 (PMID 25176261, n=60, selank vs phenazepam); and Medvedev et al. 2015 (PMID 26356395, n=70, phenazepam 30 vs selank plus phenazepam 40). PubMed tags the 2008 and 2015 papers 'Randomized Controlled Trial'; the 2014 paper is tagged 'Clinical Trial'/'Comparative Study' only. Why 'promising' and not 'proven': not one of the three is placebo-controlled — 2008 and 2014 use an active benzodiazepine comparator, 2015 tests selank as an add-on. All are small (n=60-70), all trace to a single Russian research lineage, none is independently replicated outside Russia, none has been reviewed by FDA, and full texts were not read (Russian-language, not open access) so randomisation and blinding methods are unconfirmed beyond the PubMed publication-type tag. That is a real human signal, not established efficacy. Separately: ClinicalTrials.gov registers NO selank study at all — a term search returns only fuzzy-match noise on unrelated trials. Any vendor citing a 'registered selank trial' is citing something that does not exist.", "source": { "url": "https://pubmed.ncbi.nlm.nih.gov/18454096/", "title": "[Efficacy and possible mechanisms of action of a new peptide anxiolytic selank in the therapy of generalized anxiety disorders and neurasthenia]", "publisher": "PubMed", "date": "2008-01-01" }, "verifiedAt": "2026-07-16" }, "fdaApproval": null, "fdaFindings": [ { "finding": "FDA lists 'Selank acetate (TP-7)' among bulk drug substances previously in Category 2 whose nominations were withdrawn by the nominators, and identifies immunogenicity risk and an information gap rather than a clean safety record.", "note": "Read this against the evidence tier rather than through it. Three Russian trials administered selank to roughly 190 patients in total, yet FDA still records that it 'lacks important information regarding any safety issues raised by selank acetate administered to humans.' Those are not contradictory: FDA's finding is about what was SUBMITTED AND REVIEWABLE for a compounding nomination, not about what exists in the world literature. Note too that FDA's concern is immunogenicity from aggregation and peptide-related impurities — a property of the COMPOUNDED PRODUCT and its manufacture, which no clinical trial of a well-characterised Russian formulation can speak to.", "source": { "url": "https://www.fda.gov/drugs/human-drug-compounding/certain-bulk-drug-substances-use-compounding-may-present-significant-safety-risks", "title": "Certain Bulk Drug Substances for Use in Compounding May Present Significant Safety Risks", "publisher": "FDA", "date": "2026-04-22", "quote": "Compounded drugs containing selank acetate may pose risk for immunogenicity for certain routes of administration due to the potential for aggregation and peptide-related impurities. FDA lacks important information regarding any safety issues raised by selank acetate administered to humans." }, "verifiedAt": "2026-07-16" }, { "finding": "Selank is NOT a subject of the July 23-24, 2026 Pharmacy Compounding Advisory Committee meeting. The seven substances before PCAC are BPC-157, emideltide (DSIP), epitalon, KPV, MOTS-c, semax and TB-500.", "note": "The single most likely error on this compound, and it comes from the neighbour. Semax IS before PCAC; selank is not, and FDA's semax briefing document explicitly rules selank out of scope when a selank paper appears in the semax nomination package. The two are nonetheless sold as one product — the same briefing document records vendors offering a '50:50' semax-and-selank combination nasal spray. Expect July 2026 PCAC coverage of semax to be reported as applying to selank. It does not. No PCAC briefing document for selank exists, and FDA has therefore published no staff proposal on it.", "source": { "url": "https://www.fda.gov/media/193348/download", "title": "Semax-Related Bulk Drug Substances — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, July 23-24, 2026", "publisher": "FDA", "date": "2026-07-23", "quote": "The nominations included an article describing the analgesic effects of a different peptide, selank (Meshavkin et al. 2006), which is out of the scope of this evaluation and is, therefore, not further discussed." }, "verifiedAt": "2026-07-16" }, { "finding": "FDA's safety-risk entry for selank acetate does NOT contain the 'has not identified any human exposure data' sentence that FDA applies to dihexa acetate, KPV, MOTs-C, PEG-MGF and Thymosin beta-4 fragment on the same page. Selank's entry instead refers to safety issues 'raised by selank acetate administered to humans'.", "note": "A finding about what the document does NOT say, which is why it is worth recording. The quoted sentence is FDA's KPV entry, reproduced here as the comparator — that two-part formula ('no human exposure data' + 'whether it would cause harm if administered to humans') is boilerplate FDA repeats across five other entries on this page: verbatim for dihexa acetate, KPV, MOTs-C and PEG-MGF, and near-verbatim for Thymosin beta-4 fragment, whose version drops 'on' and 'administered via any route of administration' and reads 'raised by this drug' rather than naming the substance. Selank's entry omits BOTH halves. It does not say no human exposure data exists, and it does not ask whether the substance would cause harm if administered to humans; it refers instead to issues 'raised by selank acetate administered to humans', a construction that presupposes administration has occurred. Both entries were read from the same fetch of the same page on 2026-07-16. Do not over-read this. It is a textual difference, not an FDA endorsement, and FDA has published no evaluation of the Russian trials — no PCAC briefing document for selank exists. FDA still records an immunogenicity risk and an information gap. The narrow, checkable point: the strongest negative sentence FDA has written about the peptides in this market is one it declined to write about selank.", "source": { "url": "https://www.fda.gov/drugs/human-drug-compounding/certain-bulk-drug-substances-use-compounding-may-present-significant-safety-risks", "title": "Certain Bulk Drug Substances for Use in Compounding May Present Significant Safety Risks", "publisher": "FDA", "date": "2026-04-22", "quote": "FDA has not identified any human exposure data on drug products containing KPV administered via any route of administration. FDA lacks important information regarding any safety issues raised by KPV, including whether it would cause harm if administered to humans." }, "verifiedAt": "2026-07-16" }, { "finding": "Selank appears in none of the three categories of FDA's 503A bulks list updated May 14, 2026. Category 2 of that list contains six substances — cesium chloride, domperidone, germanium sesquioxide, ibutamoren mesylate, kisspeptin-10, and quinacrine hydrochloride for intrauterine administration — and selank is not among them.", "note": "Recorded separately from legalStatus because absence and withdrawal are different facts with different sources, and collapsing them is how this gets reported wrong. This list establishes only that selank is in no category. On its own that is equally consistent with 'never nominated' and with 'approved drug that was never on the nomination track' — the reason bremelanotide is also absent. The withdrawal itself comes from FDA's nominated-but-withdrawn table, cited in legalStatus. What this list does establish, and it is the operative fact for anyone buying selank: it is not on the 503A bulks list, so a 503A pharmacy has no lawful basis to compound from it. The quoted sentence is the list's own pointer to the withdrawn table, which is what ties the two documents together.", "source": { "url": "https://www.fda.gov/media/94155/download", "title": "Bulk Drug Substances Nominated for Use in Compounding Under Section 503A of the Federal Food, Drug, and Cosmetic Act", "publisher": "FDA", "date": "2026-05-14", "quote": "Visit Safety Risks Associated with Certain Bulk Drug Substances for Use in Compounding for a summary of the identified safety risks for bulk drug substances in category 2, as well as other bulk drug substances that were previously in category 2 but were withdrawn." }, "verifiedAt": "2026-07-16" } ], "safetySignals": [ { "signal": "FDA identifies potential immunogenicity risk from aggregation and peptide-related impurities, and states it lacks important information about any safety issues raised by selank acetate administered to humans.", "note": "This is an information gap, not a clean bill of health, and it is not a documented adverse event either. Unlike BPC-157 (three FAERS reports) no FAERS signal for selank was identified in the sources read for this record — which reflects what we checked, not a demonstrated absence of harm. The Russian trials reported tolerability outcomes on the UKU scale, but their full texts were not read, so no adverse-event profile is recorded here. A blank is honest.", "source": { "url": "https://www.fda.gov/drugs/human-drug-compounding/certain-bulk-drug-substances-use-compounding-may-present-significant-safety-risks", "title": "Certain Bulk Drug Substances for Use in Compounding May Present Significant Safety Risks", "publisher": "FDA", "date": "2026-04-22" }, "verifiedAt": "2026-07-16" } ], "faqs": [ { "question": "Did Selank become legal again when FDA removed it from Category 2?", "answer": "No. Selank left FDA's Category 2 because the nominators withdrew the nominations, not because FDA cleared it — FDA's own table of substances 'previously in category 2' states they 'were withdrawn by the nominators,' and lists 'Selank acetate (TP-7)' among them. Withdrawal moved selank off the evaluation track entirely rather than toward approval: it did not enter Category 1, it is not on the 503A bulks list, and it remains non-compoundable. FDA continues to record an immunogenicity risk for compounded selank acetate on that same page.", "source": { "url": "https://www.fda.gov/drugs/human-drug-compounding/certain-bulk-drug-substances-use-compounding-may-present-significant-safety-risks", "title": "Certain Bulk Drug Substances for Use in Compounding May Present Significant Safety Risks", "publisher": "FDA", "date": "2026-04-22", "quote": "This list of bulk drug substances previously in category 2 of the interim policies were withdrawn by the nominators." }, "verifiedAt": "2026-07-16" }, { "question": "Can I get Selank from a compounding pharmacy?", "answer": "Not lawfully. Selank appears in none of the three categories of FDA's 503A bulks list updated May 14, 2026, and a 503A compounding pharmacy has no lawful basis to compound from a bulk drug substance that is not on that list. Category 2 of the list contains six substances — cesium chloride, domperidone, germanium sesquioxide, ibutamoren mesylate, kisspeptin-10, and quinacrine hydrochloride for intrauterine administration — and selank is not among them. Selank is nonetheless marketed in the United States, including as a combined product with semax, which FDA documented in its semax briefing document.", "source": { "url": "https://www.fda.gov/media/94155/download", "title": "Bulk Drug Substances Nominated for Use in Compounding Under Section 503A of the Federal Food, Drug, and Cosmetic Act", "publisher": "FDA", "date": "2026-05-14" }, "verifiedAt": "2026-07-16" }, { "question": "Is there any human evidence that Selank works?", "answer": "Yes, but it is small, Russian, and not placebo-controlled. Three trials indexed in PubMed administered selank to patients — in a 2008 trial published in Zh Nevrol Psikhiatr Im S S Korsakova, researchers studied 62 patients with generalized anxiety disorder and neurasthenia, comparing selank in 30 patients against the benzodiazepine medazepam in 32, and reported that 'the anxiolytic effects of both drugs were similar.' None of the three trials uses a placebo control, all are small, all trace to a single Russian research lineage, none has been independently replicated outside Russia, and FDA has published no evaluation of any of them. ClinicalTrials.gov registers no selank study at all.", "source": { "url": "https://pubmed.ncbi.nlm.nih.gov/18454096/", "title": "[Efficacy and possible mechanisms of action of a new peptide anxiolytic selank in the therapy of generalized anxiety disorders and neurasthenia]", "publisher": "PubMed", "date": "2008-01-01", "quote": "Sixty-two patients with generalized anxiety disorder (GAD) and neurasthenia were studied. The effect of selank (30 patients) was compared to that of medazepam (32 patients). ... The anxiolytic effects of both drugs were similar but selank had also antiasthenic and psychostimulant effects." }, "verifiedAt": "2026-07-16" }, { "question": "Is Selank part of the July 2026 FDA advisory committee meeting?", "answer": "No. Selank is not a subject of the July 23-24, 2026 Pharmacy Compounding Advisory Committee meeting; the seven substances before that committee are BPC-157, emideltide (DSIP), epitalon, KPV, MOTS-c, semax and TB-500. Semax is on that list and selank is not, despite the two being sold together as a combination product — and FDA's semax briefing document says so explicitly, ruling a selank paper 'out of the scope of this evaluation' when it appeared in the semax nomination package. No PCAC briefing document for selank exists and FDA has published no staff proposal on it.", "source": { "url": "https://www.fda.gov/media/193348/download", "title": "Semax-Related Bulk Drug Substances — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, July 23-24, 2026", "publisher": "FDA", "date": "2026-07-23", "quote": "The nominations included an article describing the analgesic effects of a different peptide, selank (Meshavkin et al. 2006), which is out of the scope of this evaluation and is, therefore, not further discussed." }, "verifiedAt": "2026-07-16" }, { "question": "Is Selank safe?", "answer": "FDA says it does not know. FDA's safety-risk page states that compounded drugs containing selank acetate 'may pose risk for immunogenicity for certain routes of administration due to the potential for aggregation and peptide-related impurities,' and that FDA 'lacks important information regarding any safety issues raised by selank acetate administered to humans.' That is an information gap rather than either a clean record or a documented harm. Note what FDA's concern attaches to: aggregation and peptide-related impurities are properties of how a compounded product is made, which no clinical trial of a different, well-characterised formulation can answer.", "source": { "url": "https://www.fda.gov/drugs/human-drug-compounding/certain-bulk-drug-substances-use-compounding-may-present-significant-safety-risks", "title": "Certain Bulk Drug Substances for Use in Compounding May Present Significant Safety Risks", "publisher": "FDA", "date": "2026-04-22", "quote": "Compounded drugs containing selank acetate may pose risk for immunogenicity for certain routes of administration due to the potential for aggregation and peptide-related impurities. FDA lacks important information regarding any safety issues raised by selank acetate administered to humans." }, "verifiedAt": "2026-07-16" } ] }, { "slug": "semaglutide", "name": "Semaglutide", "aliases": [ "Ozempic", "Wegovy", "Wegovy HD", "Rybelsus", "NN9535", "semaglutide sodium", "semaglutide acetate" ], "url": "https://peptides101.com/compounds/semaglutide", "moleculeNote": "A glucagon-like peptide-1 (GLP-1) receptor agonist. The disambiguation that matters here is not sequence but SALT FORM. FDA's approved products contain the BASE form of semaglutide. FDA has stated it received reports that compounders may be using semaglutide sodium and semaglutide acetate, and that — verbatim — 'The salt forms are different active ingredients than is used in the approved drugs, which contain the base form of semaglutide.' A vial labelled 'semaglutide' is therefore not necessarily the substance the approved products' trials studied. The aliases above list the salt forms because they are sold under this name, not because they are the same drug.", "quickAnswer": "Semaglutide is the active ingredient in drug products approved under four FDA new drug applications, all from Novo Nordisk — Ozempic injection (NDA 209637), Rybelsus and Ozempic tablets (NDA 213051), Wegovy and Wegovy HD injection (NDA 215256) and Wegovy tablets (NDA 218316). Every one of the four carries a boxed warning for risk of thyroid C-cell tumors, and their approved indications vary by product, running across type 2 diabetes, cardiovascular risk reduction, kidney outcomes in type 2 diabetes, weight management and MASH — no single product carries them all. That approval describes the approved products only. It does not extend to compounded semaglutide, to semaglutide salt forms — which FDA states are 'different active ingredients than is used in the approved drugs, which contain the base form of semaglutide' — or to vials falsely labelled 'for research purposes'. FDA has stated that semaglutide appears neither on the 503B bulks list nor on its drug shortage list, and tentatively found no clinical need for outsourcing facilities to compound with it — but that was a threshold finding, and FDA states it never reached the question of the effectiveness or lack of effectiveness of compounded semaglutide. FDA had received 990 reports of adverse events associated with compounded semaglutide as of 31 May 2026, a count it says is likely underreported, that it cannot always attribute to the drug, and many of which appear consistent with adverse events related to the approved versions.", "fdaStatus": { "value": "approved", "note": "FDA-approved. Approval is always for a specific indication and population — see the approval record below, because it is routinely not the use this is marketed for.", "source": { "url": "https://www.federalregister.gov/documents/2026/05/01/2026-08552/list-of-bulk-drug-substances-for-which-there-is-a-clinical-need-under-section-503b-of-the-federal", "title": "List of Bulk Drug Substances for Which There Is a Clinical Need Under Section 503B of the Federal Food, Drug, and Cosmetic Act", "publisher": "FDA", "date": "2026-05-01", "quote": "Semaglutide is an active ingredient in FDA-approved drug products: 2 mg/3 mL, 4 mg/3 mL, and 8 mg/3 mL solutions for subcutaneous (SC) injection which contain propylene glycol (Ozempic, NDA 209637); … (Wegovy and Wegovy HD, NDA 215256); … oral tablets (Wegovy, NDA 218316); and … oral tablets (Rybelsus and Ozempic, NDA 213051)." }, "verifiedAt": "2026-07-16" }, "compoundingStatus": null, "evidence": { "tier": "proven-in-humans", "humanAdministrationChecked": true, "note": "Administration check RUN, not assumed. SELECT (NCT03574597) was opened and read on 2026-07-16: intervention type DRUG, semaglutide administered subcutaneously versus placebo, Phase 3, enrolment 17,604 ACTUAL, lead sponsor Novo Nordisk A/S, status COMPLETED (primary completion 2023-06-21 ACTUAL; completion 2023-06-29 ACTUAL; results first posted 2024-08-30), hasResults true. The `date` field above carries the primary completion date. Semaglutide was ADMINISTERED to humans — it was not measured as an endogenous biomarker, which is the trap that reduces MOTS-c and TB-500 from an apparent five human RCTs to an actual zero. Independently corroborated against section 14.1 of the FDA-approved WEGOVY label, which describes the same trial. This registration is also clean of the contamination in this vertical: it is not a Hudson Biotech registration, not a February-2026 recruiting shell, and not a relabelled clone. SCOPE — the tier attaches to the approved indications and to the approved base-form products, and to nothing else. It does not transfer to salt forms, to compounded combinations, or to indications outside the label. A large trial of one product is not evidence for a different product sold under the same name.", "source": { "url": "https://clinicaltrials.gov/study/NCT03574597", "title": "SELECT — Semaglutide Effects on Cardiovascular Outcomes in People With Overweight or Obesity", "publisher": "ClinicalTrials.gov", "date": "2023-06-21" }, "verifiedAt": "2026-07-16" }, "fdaApproval": { "applicationNumber": "NDA 209637 (Ozempic injection); NDA 213051 (Rybelsus and Ozempic tablets); NDA 215256 (Wegovy and Wegovy HD injection); NDA 218316 (Wegovy tablets)", "brandName": "Ozempic, Wegovy, Wegovy HD, Rybelsus", "approvedIndication": "WEGOVY injection is indicated in combination with a reduced calorie diet and increased physical activity: • To reduce the risk of major adverse cardiovascular (CV) events (CV death, non-fatal myocardial infarction, or non-fatal stroke) in adults with established CV disease and either obesity or overweight. • To reduce excess body weight and maintain weight reduction long term in: o Adults and pediatric patients aged 12 years and older with obesity. o Adults with overweight in the presence of at least one weight-related comorbid condition. • For the treatment of noncirrhotic metabolic dysfunction-associated steatohepatitis (MASH), formerly known as nonalcoholic steatohepatitis (NASH), with moderate to advanced liver fibrosis (consistent with stages F2 to F3 fibrosis) in adults. This indication is approved under accelerated approval based on improvement of MASH and fibrosis. — WEGOVY tablets are indicated in combination with a reduced calorie diet and increased physical activity: • To reduce the risk of major adverse CV events (CV death, non-fatal myocardial infarction, or non-fatal stroke) in adults with established CV disease and either obesity or overweight. • To reduce excess body weight and maintain weight reduction long term in adults with obesity, or in adults with overweight in the presence of at least one weight-related comorbid condition.", "discontinued": false, "source": { "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2026/215256s029lbl.pdf", "title": "WEGOVY (semaglutide) injection / tablets — Highlights of Prescribing Information", "publisher": "FDA", "date": "2026-03-23" }, "verifiedAt": "2026-07-16" }, "fdaFindings": [ { "finding": "FDA tentatively finds no basis to conclude there is a clinical need for an outsourcing facility to compound using semaglutide, and proposes not to include it on the 503B Bulks List.", "note": "Two distinctions the coverage collapses. This is 503B (outsourcing facilities), NOT the 503A bulks list that BPC-157 and the consumer peptides sit against — different statute, different list, different test. And it is a TENTATIVE finding in a proposed notice, not a final determination; the comment period closed 2026-06-30. What FDA actually evaluated is narrow and specific: whether the approved products are MEDICALLY UNSUITABLE for identified patients. It found the nominations did not identify any such unsuitability.", "source": { "url": "https://www.federalregister.gov/documents/2026/05/01/2026-08552/list-of-bulk-drug-substances-for-which-there-is-a-clinical-need-under-section-503b-of-the-federal", "title": "List of Bulk Drug Substances for Which There Is a Clinical Need Under Section 503B of the Federal Food, Drug, and Cosmetic Act", "publisher": "FDA", "date": "2026-05-01", "quote": "FDA tentatively finds no basis to conclude that there is a clinical need for an outsourcing facility to compound using the following bulk drug substances: semaglutide, tirzepatide, and liraglutide. Therefore, we propose not to include these bulk drug substances on the 503B Bulks List." }, "verifiedAt": "2026-07-16" }, { "finding": "OZEMPIC (NDA 209637) is indicated: as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus; to reduce the risk of major adverse cardiovascular events (cardiovascular death, non-fatal myocardial infarction or non-fatal stroke) in adults with type 2 diabetes mellitus and established cardiovascular disease; to reduce the risk of sustained eGFR decline, end-stage kidney disease, and cardiovascular death in adults with type 2 diabetes mellitus and chronic kidney disease.", "note": "Recorded verbatim because the brand-name gap is the whole point. EVERY Ozempic indication is gated on 'adults with type 2 diabetes mellitus'. Ozempic is not approved for weight management in patients without type 2 diabetes — Wegovy is the semaglutide product with the obesity indications. FDA itself flags the asymmetry in the 503B notice, whose sentence is quoted in full because the appositive is load-bearing: 'Wegovy and Wegovy HD, the approved formulations that do not contain propylene glycol, have not been shown to be safe and effective for the treatment of type 2 diabetes.' Same molecule, same sponsor, non-interchangeable approvals in both directions. That sentence is NOT in this field's source — it is in the Federal Register notice, and it is cited to that document in the FAQ that turns on it.", "source": { "url": "https://www.accessdata.fda.gov/spl/data/341dc8b9-9576-48a7-b8d8-c583c67b7007/341dc8b9-9576-48a7-b8d8-c583c67b7007.xml", "title": "OZEMPIC (semaglutide) injection — Highlights of Prescribing Information (SPL)", "publisher": "FDA", "date": "2025-10-14" }, "verifiedAt": "2026-07-16" }, { "finding": "RYBELSUS and OZEMPIC tablets (NDA 213051) are indicated: as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus; to reduce the risk of major adverse cardiovascular (CV) events (CV death, non-fatal myocardial infarction or non-fatal stroke) in adults with type 2 diabetes mellitus who are at high risk for these events.", "note": "The fourth NDA, recorded verbatim so that the record's own four-NDA framing is carried by four sourced labels rather than three. Read the gating: both indications are confined to 'adults with type 2 diabetes mellitus', and the CV indication is narrower still — it requires patients 'at high risk for these events', where Wegovy's CV indication requires established CV disease with obesity or overweight. Note the brand-name collision this label documents: OZEMPIC is a brand name under TWO different NDAs — the injection (NDA 209637) and the tablets shipped under this one. 'Ozempic' does not identify a product.", "source": { "url": "https://www.accessdata.fda.gov/spl/data/5176eed4-f8f8-4f88-a079-11f16864f40a/5176eed4-f8f8-4f88-a079-11f16864f40a.xml", "title": "RYBELSUS and OZEMPIC (semaglutide) tablets — Highlights of Prescribing Information (SPL)", "publisher": "FDA", "date": "2026-01-30", "quote": "RYBELSUS and OZEMPIC tablets are indicated: • as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. • to reduce the risk of major adverse cardiovascular (CV) events (CV death, non-fatal myocardial infarction or non-fatal stroke) in adults with type 2 diabetes mellitus who are at high risk for these events." }, "verifiedAt": "2026-07-16" }, { "finding": "FDA has stated that semaglutide salt forms — semaglutide sodium and semaglutide acetate — are different active ingredients than the base form used in the approved drugs, and that it is not aware of any basis for compounding with them that would meet the FD&C Act conditions for active ingredients that can be used in compounding.", "note": "The single most load-bearing sentence for anyone buying something labelled 'semaglutide' that is not an approved product. FDA is not saying the salt is a lower-grade semaglutide. It is saying it is a DIFFERENT ACTIVE INGREDIENT — which means the approval, the label and the trials behind them do not describe it. Note this page is stale in one respect: it states 'three FDA-approved semaglutide products', which was true on 2024-07-26 and is not true now (four NDAs). The salt-form finding is unaffected.", "source": { "url": "https://www.fda.gov/drugs/human-drug-compounding/fda-alerts-health-care-providers-compounders-and-patients-dosing-errors-associated-compounded", "title": "FDA alerts health care providers, compounders and patients of dosing errors associated with compounded injectable semaglutide products", "publisher": "FDA", "date": "2024-07-26", "quote": "The salt forms are different active ingredients than is used in the approved drugs, which contain the base form of semaglutide. The FDA is not aware of any basis for compounding using the salt forms that would meet the FD&C Act conditions for types of active ingredients that can be used in compounding." }, "verifiedAt": "2026-07-16" }, { "finding": "FDA has stated it may consider a compounded drug product combining semaglutide API with another API, such as vitamin B12 (cyanocobalamin), to be essentially a copy of a commercially available drug product.", "note": "Names the exact product the compounding market built to argue it was NOT making copies. The 'significant difference' escape requires a prescriber to determine and document a significant difference for an identified individual patient — a per-patient finding, not a product design. Adding B12 to a formulation is not, by itself, that finding.", "source": { "url": "https://www.fda.gov/drugs/drug-alerts-and-statements/fda-clarifies-policies-compounders-national-glp-1-supply-begins-stabilize", "title": "FDA clarifies policies for compounders as national GLP-1 supply begins to stabilize", "publisher": "FDA", "date": "2026-04-01" }, "verifiedAt": "2026-07-16" }, { "finding": "In a published phase 2 trial cited by a nominator (NCT05486065, Aroda et al. 2025), FDA reported a MIXED result. Neither higher-dose semaglutide arm demonstrated a statistically significant improvement in glycemic control (HbA1c) compared with the lower-dose arm using the treatment policy estimand. On body weight, the highest-dose arm DID show a statistically significant decrease versus the lower-dose arm using that estimand, while the intermediate-dose arm did not. Adverse events and treatment discontinuations due to adverse events were more frequent in both higher-dose arms than in the lower-dose arm.", "note": "This one runs BACKWARDS to the market's premise, which is why it is here — but it must be read as the mixed result it is, not as a clean negative. A nominator cited this trial while it was unpublished, to argue that higher doses than the approved products allow have a 'superior effect' and that compounding was therefore needed to supply them. It published. The nominator's argument was about medical unsuitability of the approved products, and FDA's characterisation of the published result is blunt: the results 'do not support the nominator's argument'. Read precisely: the one endpoint that did separate was body weight, and only at the highest dose — the intermediate dose did not separate on either endpoint, so the trial does not describe a dose-response the more-is-better case needs. Both higher arms carried more adverse events and more discontinuations. A single significant weight endpoint in a phase 2 trial is not a finding that the approved products fail to achieve their intended clinical benefit, which is the question FDA was answering. QUOTE HANDLING: the Federal Register names the specific milligram strengths of each arm. They are replaced above with bracketed descriptors ([highest], [intermediate], [lowest]) under this site's no-dosing policy — a dose-to-outcome mapping is the actionable part for someone self-administering an unapproved vial. Nothing else in the quote is altered, and no finding depends on the elided figures.", "source": { "url": "https://www.federalregister.gov/documents/2026/05/01/2026-08552/list-of-bulk-drug-substances-for-which-there-is-a-clinical-need-under-section-503b-of-the-federal", "title": "List of Bulk Drug Substances for Which There Is a Clinical Need Under Section 503B of the Federal Food, Drug, and Cosmetic Act", "publisher": "FDA", "date": "2026-05-01", "quote": "The results do not support the nominator's argument. … The study did not demonstrate a statistically significant improvement in glycemic control (as measured by hemoglobin A1c) … using the treatment policy estimand. There was a statistically significant decrease in body weight when the semaglutide [highest] dose was compared to the [lowest] dose using the treatment policy estimand, but the study did not demonstrate a statistically significant decrease in body weight when the [intermediate] dose was compared to the [lowest] dose. We note that adverse events and treatment discontinuations due to adverse events were more frequent in the [two higher] groups than in the [lowest] dose group." }, "verifiedAt": "2026-07-16" }, { "finding": "FDA has stated that neither semaglutide nor tirzepatide currently appears on the 503B bulks list or on FDA's drug shortage list, and that outsourcing facilities are restricted from compounding with a bulk drug substance unless it appears on the 503B bulks list or the drug compounded from it is on FDA's drug shortage list at the time of compounding, distribution and dispensing.", "note": "The two-sentence answer to 'is compounded semaglutide legal', and the reason the market's 2023-2024 arrangement no longer exists. Read the mechanism, not the vibe. Both statutory doors for 503B compounding are conditional, and FDA states both conditions are now unmet: semaglutide is not on the 503B bulks list (it was evaluated and FDA proposed not to add it — see the tentative finding above), and it is not on the shortage list (FDA determined on 2025-02-21 that the shortage of semaglutide injection products was resolved, having confirmed with the manufacturer that stated availability and manufacturing capacity could meet present and projected national demand). The shortage listing is what the entire compounded-GLP-1 telehealth industry was built on, and it is what closed. TIMELINE, because the dates are load-bearing and are widely misreported — including by this record until it was corrected. FDA's 503A wind-down was NOT a fixed 2025-04-22 deadline: FDA wrote that it did not intend to act against a 503A pharmacy or physician 'until April 22, 2025, or until the date of the district court's decision on the plaintiffs' forthcoming preliminary injunction motion in Outsourcing Facilities Association (OFA) v. FDA, 4:25-cv-00174 (N.D. Tex.), whichever is later'. The court denied that motion on 2025-04-24, which was later, so the 503A period ran to 2025-04-24. The 503B period ran to 2025-05-22, unaffected because that date postdates the decision. FDA then stated that for 503A pharmacies and physicians the period of enforcement discretion 'has ended'. This did not go the compounders' way and it is not still pending. SCOPE: this finding is about compounding from BULK semaglutide. It is not a statement that no lawful compounding of any kind can occur, and it is not a criminal-law statement.", "source": { "url": "https://www.fda.gov/drugs/drug-alerts-and-statements/fda-clarifies-policies-compounders-national-glp-1-supply-begins-stabilize", "title": "FDA clarifies policies for compounders as national GLP-1 supply begins to stabilize", "publisher": "FDA", "date": "2026-04-01", "quote": "Tirzepatide and semaglutide do not currently appear on the 503B bulks list or on FDA's drug shortage list." }, "verifiedAt": "2026-07-16" }, { "finding": "FDA did not evaluate whether compounded semaglutide is effective. FDA stated that because the nomination did not pass through Part 1(a) of its clinical-need analysis, it did not reach Part 2 and therefore did not consider the Part 2 factors, including the available evidence of effectiveness or lack of effectiveness of a drug product compounded with semaglutide.", "note": "Recorded because it is the finding that cuts BOTH ways, and both misreadings are live. Sellers read FDA's silence as an absence of adverse findings; critics read FDA's proposal as a determination that compounded semaglutide does not work. Neither is what happened. FDA's clinical-need test is sequential: Part 1(a) asks the threshold question of whether the nomination identifies an attribute of the approved drug making it medically unsuitable for identified patients. The nomination failed there, so the analysis stopped there, and the effectiveness question was never opened. On this record FDA has expressed no view on whether compounded semaglutide works. That is a genuine blank, and this site records blanks rather than filling them.", "source": { "url": "https://www.federalregister.gov/documents/2026/05/01/2026-08552/list-of-bulk-drug-substances-for-which-there-is-a-clinical-need-under-section-503b-of-the-federal", "title": "List of Bulk Drug Substances for Which There Is a Clinical Need Under Section 503B of the Federal Food, Drug, and Cosmetic Act", "publisher": "FDA", "date": "2026-05-01", "quote": "Because this nomination did not pass through Part 1(a), we did not reach Part 2 and therefore did not consider the Part 2 factors, including the available evidence of effectiveness or lack of effectiveness of a drug product compounded with semaglutide." }, "verifiedAt": "2026-07-16" }, { "finding": "On nominations to compound semaglutide for sublingual and buccal administration, FDA stated that the nominators referred to concerns about oral routes of administration generally and did not identify any unsuitability with the approved semaglutide products, nor explain why the injectable products would be medically unsuitable for patients who cannot swallow a tablet.", "note": "Directly on point for sublingual and 'oral drop' semaglutide, which is sold as an established alternative to injection. It was nominated as one, and it was evaluated: FDA recorded that semaglutide was nominated for the subcutaneous, sublingual, buccal and oral routes. Note what FDA does NOT do here — it does not dispute that dysphagia is real or that compounding serves patients who cannot swallow tablets. It concedes both. The failure is one of specificity: a general concern about swallowing is not a finding about THESE products, one of which is an injection. The single paper the nominator offered was characterised by its own authors as a guideline for future investigators, and FDA noted the authors 'did not design their study to assess, and, accordingly, do not identify, any medical unsuitability of FDA-approved GLP-1 receptor agonists' and that the paper discusses GLP-1 drugs generally rather than the approved semaglutide products.", "source": { "url": "https://www.federalregister.gov/documents/2026/05/01/2026-08552/list-of-bulk-drug-substances-for-which-there-is-a-clinical-need-under-section-503b-of-the-federal", "title": "List of Bulk Drug Substances for Which There Is a Clinical Need Under Section 503B of the Federal Food, Drug, and Cosmetic Act", "publisher": "FDA", "date": "2026-05-01", "quote": "While we have no reason to disagree with the proposition that difficulty swallowing is a \"well-documented issue\" and that compounded drugs can serve an important need for patients who cannot swallow tablets, the nominators refer to concerns about oral routes of administration generally; they do not identify any unsuitability with approved semaglutide products. Nor do they explain why the injectable drug products would be medically unsuitable for patients who cannot swallow a tablet." }, "verifiedAt": "2026-07-16" }, { "finding": "On the claim that some patients are 'hyper-responders' who need strengths other than those commercially available, FDA reported that the nominator provided no reference supporting its statement that 5-15% of the population are hyper-responders, and that the study the nominator cited (Wilding et al. 2021) does not mention 'hyper-responders' or the 5-15% statistic at all.", "note": "This is FDA opening the citation and finding it does not say what it was cited for — the same failure mode this site exists to correct, caught here by the regulator, in a filing, against a party with counsel. The 'hyper-responder' concept is a load-bearing premise of personalised-GLP-1 marketing. FDA also recorded that the nominators did not explain why a patient needing a lower maintenance strength could not use one of the approved products that contain a lower concentration, and did not explain why a slower escalation using the approved products could not be used in patients who do not tolerate escalation. The specific figures in FDA's reasoning are elided here under this site's no-dosing policy; no finding depends on them.", "source": { "url": "https://www.federalregister.gov/documents/2026/05/01/2026-08552/list-of-bulk-drug-substances-for-which-there-is-a-clinical-need-under-section-503b-of-the-federal", "title": "List of Bulk Drug Substances for Which There Is a Clinical Need Under Section 503B of the Federal Food, Drug, and Cosmetic Act", "publisher": "FDA", "date": "2026-05-01", "quote": "The nominator provides no reference that supports its statement about what \"has been estimated.\" The nominator cites Wilding et al. (2021), which does not mention \"hyper-responders\" or the 5-15% statistic (Ref. 3)." }, "verifiedAt": "2026-07-16" }, { "finding": "FDA stated it has not identified any data or information to suggest that propylene glycol would cause a drug product containing semaglutide to be medically unsuitable, and noted that the approved propylene-glycol-free formulations of Wegovy and Wegovy HD are themselves labeled for injection site reactions.", "note": "The 'preservative-free / PG-free' compounded pitch, evaluated and not sustained. FDA's reasoning is worth reading because it is empirical rather than dismissive: injection site reaction is reported in trials of injectable therapeutics not formulated with propylene glycol at all, including insulins and other GLP-1 receptor agonists; the approved PG-free semaglutide products carry the same labeled reaction. FDA noted that 'the presence of propylene glycol in Ozempic and the absence of this excipient in Wegovy suggests that determinants of injection site reactions are likely more complex than the inclusion or exclusion of propylene glycol in the formulation'. The one FAERS report FDA discussed involved a patient with a history of severe propylene glycol allergy, and FDA's assessment was that 'It is unclear whether the reaction experienced can be attributed to propylene glycol'. Crucially, FDA added that even if PG-containing formulations were unsuitable for some patients, the nominator gave no basis to conclude those patients could not use the approved products that are PG-free — an approved product already answers the stated need.", "source": { "url": "https://www.federalregister.gov/documents/2026/05/01/2026-08552/list-of-bulk-drug-substances-for-which-there-is-a-clinical-need-under-section-503b-of-the-federal", "title": "List of Bulk Drug Substances for Which There Is a Clinical Need Under Section 503B of the Federal Food, Drug, and Cosmetic Act", "publisher": "FDA", "date": "2026-05-01", "quote": "FDA has not identified any data or information to suggest that propylene glycol would cause a drug product containing semaglutide to be medically unsuitable." }, "verifiedAt": "2026-07-16" }, { "finding": "FDA has warned companies that illegally sold unapproved drugs containing semaglutide, tirzepatide or retatrutide that were falsely labeled 'for research purposes' or 'not for human consumption', stating these products have been sold directly to consumers for human use with dosing instructions.", "note": "The research-label theory, addressed by FDA on the compound where the most money rides on it. Note FDA's verb: 'falsely labeled'. The label is not treated as a disclaimer that changes what the product is — it is treated as a false statement about it, and the sale is characterised as illegal notwithstanding the wording on the vial. FDA's stated tell is that the products ship to consumers with dosing instructions, which is conduct inconsistent with the label the seller chose. This is the same failed theory FDA has held against twice elsewhere in 2026; semaglutide is simply where it is most lucrative.", "source": { "url": "https://www.fda.gov/drugs/drug-alerts-and-statements/fdas-concerns-unapproved-glp-1-drugs-used-weight-loss", "title": "FDA's Concerns with Unapproved GLP-1 Drugs Used for Weight Loss", "publisher": "FDA", "date": "2026-06-15", "quote": "FDA has warned companies that have illegally sold unapproved drugs containing semaglutide, tirzepatide or retatrutide that are falsely labeled \"for research purposes\" or \"not for human consumption.\" These products have been sold directly to consumers for human use with dosing instructions." }, "verifiedAt": "2026-07-16" }, { "finding": "Semaglutide appears in none of Categories 1, 2 or 3 of the 503A bulk drug substances list updated 2026-05-14.", "note": "Recorded to close a misreading, not to assert a status. Verified by fetching and text-extracting the document directly: no hit for 'semaglutide' anywhere. This absence means something entirely different from BPC-157's absence. BPC-157 was nominated and left Category 2 when the nominators withdrew. Semaglutide was never in this system at all — a 503A bulks nomination is a route for substances WITHOUT an approved product, and semaglutide has four. Categorical silence here is neither permission nor a safety finding.", "source": { "url": "https://www.fda.gov/media/94155/download", "title": "Bulk Drug Substances Nominated for Use in Compounding Under Section 503A of the Federal Food, Drug, and Cosmetic Act", "publisher": "FDA", "date": "2026-05-14" }, "verifiedAt": "2026-07-16" } ], "safetySignals": [ { "signal": "Boxed warning — risk of thyroid C-cell tumors. In rodents, semaglutide causes thyroid C-cell tumors at clinically relevant exposures. It is unknown whether it causes thyroid C-cell tumors, including medullary thyroid carcinoma (MTC), in humans, as the human relevance of semaglutide-induced rodent thyroid C-cell tumors has not been determined. Contraindicated in patients with a personal or family history of MTC or in patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2).", "note": "FDA's highest-level warning, and it sits on the most-prescribed peptide in the country. This entry covers NDA 215256 and NDA 218316 only, which is what its source covers. The other two NDAs carry the same boxed warning and are recorded separately below, against their own labels — the quickAnswer says every one of the four applications carries it, and a claim about four labels needs four labels. The contraindication is a screening question a purchaser of an unapproved product is never asked, because there is no label to ask it.", "source": { "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2026/215256s029lbl.pdf", "title": "WEGOVY (semaglutide) injection / tablets — Highlights of Prescribing Information", "publisher": "FDA", "date": "2026-03-23", "quote": "In rodents, semaglutide causes thyroid C-cell tumors at clinically relevant exposures. It is unknown whether WEGOVY causes thyroid C-cell tumors, including medullary thyroid carcinoma (MTC), in humans as the human relevance of semaglutide-induced rodent thyroid C-cell tumors has not been determined." }, "verifiedAt": "2026-07-16" }, { "signal": "Boxed warning — risk of thyroid C-cell tumors, on OZEMPIC injection (NDA 209637). In rodents, semaglutide causes dose-dependent and treatment-duration-dependent thyroid C-cell tumors at clinically relevant exposures. It is unknown whether OZEMPIC causes thyroid C-cell tumors, including medullary thyroid carcinoma (MTC), in humans.", "note": "Recorded as its own sourced entry rather than left as an aside inside another entry's note, which is where it previously lived. Note the wording this label carries that the Wegovy label does not: 'dose-dependent and treatment-duration-dependent'.", "source": { "url": "https://www.accessdata.fda.gov/spl/data/341dc8b9-9576-48a7-b8d8-c583c67b7007/341dc8b9-9576-48a7-b8d8-c583c67b7007.xml", "title": "OZEMPIC (semaglutide) injection — Highlights of Prescribing Information (SPL)", "publisher": "FDA", "date": "2025-10-14", "quote": "In rodents, semaglutide causes dose-dependent and treatment-duration-dependent thyroid C-cell tumors at clinically relevant exposures. It is unknown whether OZEMPIC causes thyroid C-cell tumors, including medullary thyroid carcinoma (MTC), in humans as human relevance of semaglutide-induced rodent thyroid C-cell tumors has not been determined." }, "verifiedAt": "2026-07-16" }, { "signal": "Boxed warning — risk of thyroid C-cell tumors, on RYBELSUS and OZEMPIC tablets (NDA 213051). In rodents, semaglutide causes dose-dependent and treatment-duration-dependent thyroid C-cell tumors at clinically relevant exposures. It is unknown whether RYBELSUS and OZEMPIC tablets cause thyroid C-cell tumors, including medullary thyroid carcinoma (MTC), in humans.", "note": "The fourth NDA's boxed warning, previously unsourced anywhere on this record. Worth recording on its own because it defeats the intuition the oral route invites: these are tablets, not injections, and they carry the identical boxed warning and the identical MTC and MEN 2 contraindication. Route of administration is not the risk axis here.", "source": { "url": "https://www.accessdata.fda.gov/spl/data/5176eed4-f8f8-4f88-a079-11f16864f40a/5176eed4-f8f8-4f88-a079-11f16864f40a.xml", "title": "RYBELSUS and OZEMPIC (semaglutide) tablets — Highlights of Prescribing Information (SPL)", "publisher": "FDA", "date": "2026-01-30", "quote": "In rodents, semaglutide causes dose-dependent and treatment-duration-dependent thyroid C-cell tumors at clinically relevant exposures. It is unknown whether RYBELSUS and OZEMPIC tablets cause thyroid C-cell tumors, including medullary thyroid carcinoma (MTC), in humans as human relevance of semaglutide-induced rodent thyroid C-cell tumors has not been determined." }, "verifiedAt": "2026-07-16" }, { "signal": "FDA has received reports of adverse events, some requiring hospitalization, that may be related to overdoses due to dosing errors associated with compounded semaglutide injectable products.", "note": "The harm here is not the molecule — it is the presentation. FDA attributes the errors to patients measuring and self-administering incorrect amounts and to providers miscalculating, noting that many patients receiving vials 'lacked experience with self-injections' and that 'confusion between different units of measurement (e.g., milliliters, milligrams and \"units\")' may have contributed. The approved products are pens delivering a preset amount; the compounded products are vials and syringes. FDA also notes a prolonged period of observation may be necessary given semaglutide's long half-life of about one week. This is the clearest case on the site that the same verified molecule is not the same risk once it leaves the approved product.", "source": { "url": "https://www.fda.gov/drugs/human-drug-compounding/fda-alerts-health-care-providers-compounders-and-patients-dosing-errors-associated-compounded", "title": "FDA alerts health care providers, compounders and patients of dosing errors associated with compounded injectable semaglutide products", "publisher": "FDA", "date": "2024-07-26", "quote": "FDA has received reports of adverse events, some requiring hospitalization, that may be related to overdoses due to dosing errors associated with compounded semaglutide injectable products." }, "verifiedAt": "2026-07-16" }, { "signal": "Labeled warnings and precautions include acute pancreatitis, acute gallbladder disease, hypoglycemia (with concomitant insulin or insulin secretagogue), acute kidney injury due to volume depletion, severe gastrointestinal adverse reactions, hypersensitivity reactions including anaphylaxis and angioedema reported postmarketing, diabetic retinopathy complications in patients with type 2 diabetes, heart rate increase, and pulmonary aspiration during general anesthesia or deep sedation.", "note": "Reproduced because 'well-tolerated' is doing heavy lifting in the marketing. Most common adverse reactions at incidence 5% or greater in adults or paediatric patients aged 12 and older, per the label: nausea, diarrhea, vomiting, constipation, abdominal pain, dysesthesia, headache, fatigue, dyspepsia, dizziness, abdominal distension, eructation, hypoglycemia in patients with type 2 diabetes, flatulence, gastroenteritis, gastroesophageal reflux disease, and hair loss.", "source": { "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2026/215256s029lbl.pdf", "title": "WEGOVY (semaglutide) injection / tablets — Highlights of Prescribing Information", "publisher": "FDA", "date": "2026-03-23" }, "verifiedAt": "2026-07-16" }, { "signal": "As of 31 May 2026, FDA had received 990 reports of adverse events associated with compounded semaglutide. FDA attaches three qualifications to that count. It states that federal law does not require state-licensed pharmacies that are not outsourcing facilities to submit adverse events to FDA, so it is likely that adverse events from compounded versions of these drugs are underreported; that many of the adverse events reported for compounded products appear to be consistent with adverse events related to the FDA-approved versions of these products; and that it is not always possible to determine if the adverse event directly resulted from use of the drug or if other factors may have contributed.", "note": "The only hard count FDA publishes on compounded semaglutide, and the only place on this site where a compound has one. It must be read with all three of FDA's own caveats attached, or it becomes propaganda in either direction. (1) FDA states 'It is not always possible to determine if the adverse event directly resulted from use of the drug or if other factors may have contributed' — 990 reports is not 990 injuries caused. (2) FDA states many of the adverse events reported for compounded products 'appear to be consistent with adverse events related to the FDA-approved versions' — much of this is the drug behaving as the label says it behaves, not a compounding-specific harm. (3) The underreporting point above is structural and cuts the other way: the reporting duty that generates these numbers does not reach the pharmacies dispensing most of this product, so 990 is a floor of unknown height, not a rate. A denominator does not exist. Anyone quoting this number as a risk rate is inventing the part that matters. The comparable figure for compounded tirzepatide was more than 730.", "source": { "url": "https://www.fda.gov/drugs/drug-alerts-and-statements/fdas-concerns-unapproved-glp-1-drugs-used-weight-loss", "title": "FDA's Concerns with Unapproved GLP-1 Drugs Used for Weight Loss", "publisher": "FDA", "date": "2026-06-15", "quote": "FDA has received reports of adverse events related to compounded versions of semaglutide and tirzepatide. However, federal law does not require state-licensed pharmacies that are not outsourcing facilities to submit adverse events to FDA so it is likely that adverse events from compounded versions of these drugs are underreported. Many of the adverse events reported for compounded products appear to be consistent with adverse events related to the FDA-approved versions of these products. As of May 31, 2026, the FDA has received: 990 reports of adverse events associated with compounded semaglutide. … It is not always possible to determine if the adverse event directly resulted from use of the drug or if other factors may have contributed to these adverse events." }, "verifiedAt": "2026-07-16" }, { "signal": "FDA has stated it is aware of fraudulent compounded semaglutide marketed in the U.S. that contains false information on the product label — in some cases the compounding pharmacies identified on the labels do not exist, and in other cases the labels name a licensed pharmacy that, based on information FDA gathered, did not compound the products.", "note": "The signal that defeats the standard consumer check. The advice everywhere is to verify the compounding pharmacy on the label; FDA is reporting that the pharmacy on the label is sometimes fictional, and sometimes a real pharmacy that had nothing to do with the vial. A label naming a pharmacy that does exist is therefore not evidence that pharmacy made it. FDA has also established a green list import alert (66-80) directed at GLP-1 active pharmaceutical ingredients with potential quality concerns, and separately warns of counterfeit Ozempic in the U.S. drug supply chain. This is a supply-chain finding, not a pharmacology finding: it says nothing about semaglutide the molecule and everything about what is in an unverifiable vial.", "source": { "url": "https://www.fda.gov/drugs/drug-alerts-and-statements/fdas-concerns-unapproved-glp-1-drugs-used-weight-loss", "title": "FDA's Concerns with Unapproved GLP-1 Drugs Used for Weight Loss", "publisher": "FDA", "date": "2026-06-15", "quote": "FDA is aware of fraudulent compounded semaglutide and tirzepatide marketed in the U.S. that contain false information on the product label. In some cases, the compounding pharmacies identified on the labels of the products do not exist." }, "verifiedAt": "2026-07-16" } ], "faqs": [ { "question": "Is compounded semaglutide legal in 2026?", "answer": "Compounding semaglutide from bulk drug substance at an outsourcing facility is not permitted, because both of the statutory conditions that would allow it are unmet. FDA states that outsourcing facilities are restricted from compounding with a bulk drug substance unless the substance appears on the 503B bulks list, or the drug compounded from it is on FDA's drug shortage list at the time of compounding, distribution and dispensing — and that, as of 1 April 2026, 'Tirzepatide and semaglutide do not currently appear on the 503B bulks list or on FDA's drug shortage list.' The shortage listing is what the compounded-GLP-1 industry was built on and it closed: FDA determined on 21 February 2025 that the shortage of semaglutide injection products was resolved. The wind-down for state-licensed pharmacies and physicians compounding under section 503A ran, in FDA's own words, 'until April 22, 2025, or until the date of the district court's decision on the plaintiffs' forthcoming preliminary injunction motion in Outsourcing Facilities Association (OFA) v. FDA, 4:25-cv-00174 (N.D. Tex.), whichever is later' — the court denied that motion on 24 April 2025, so the 503A period ran to 24 April 2025, not 22 April. For outsourcing facilities under section 503B it ran to 22 May 2025. FDA states that for 503A compounding the period of enforcement discretion 'has ended'. Semaglutide is a component of FDA-approved drugs, so this is not a blanket prohibition on every form of compounding — but a compounded product that duplicates an approved one runs into the separate 'essentially a copy' restriction, which requires a prescriber to determine and document a significant difference for an identified individual patient.", "source": { "url": "https://www.fda.gov/drugs/drug-alerts-and-statements/fda-clarifies-policies-compounders-national-glp-1-supply-begins-stabilize", "title": "FDA clarifies policies for compounders as national GLP-1 supply begins to stabilize", "publisher": "FDA", "date": "2026-04-01", "quote": "Tirzepatide and semaglutide do not currently appear on the 503B bulks list or on FDA's drug shortage list." }, "verifiedAt": "2026-07-16" }, { "question": "Is Ozempic approved for weight loss?", "answer": "No. Every indication in the FDA-approved labeling for Ozempic (semaglutide injection, NDA 209637) is restricted to adults with type 2 diabetes mellitus: improving glycemic control as an adjunct to diet and exercise; reducing the risk of major adverse cardiovascular events in adults with type 2 diabetes and established cardiovascular disease; and reducing the risk of sustained eGFR decline, end-stage kidney disease and cardiovascular death in adults with type 2 diabetes and chronic kidney disease. Weight loss is not among them. Prescribing Ozempic for weight loss in a patient without type 2 diabetes is off-label use, which is a decision for a licensed prescriber and is not something this label supports. Note also that 'Ozempic' names products under two different applications — the injection under NDA 209637 described here, and the tablets under NDA 213051, whose own label is likewise confined to adults with type 2 diabetes mellitus.", "source": { "url": "https://www.accessdata.fda.gov/spl/data/341dc8b9-9576-48a7-b8d8-c583c67b7007/341dc8b9-9576-48a7-b8d8-c583c67b7007.xml", "title": "OZEMPIC (semaglutide) injection — Highlights of Prescribing Information (SPL)", "publisher": "FDA", "date": "2025-10-14", "quote": "OZEMPIC is indicated: • as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. • to reduce the risk of major adverse cardiovascular events (cardiovascular death, non-fatal myocardial infarction or non-fatal stroke) in adults with type 2 diabetes mellitus and established cardiovascular disease. • to reduce the risk of sustained eGFR decline, end-stage kidney disease, and cardiovascular death in adults with type 2 diabetes mellitus and chronic kidney disease." }, "verifiedAt": "2026-07-16" }, { "question": "Can I use Wegovy instead of Ozempic if I have type 2 diabetes?", "answer": "Not on the strength of the label. The two are the same molecule from the same sponsor, but their approvals are not interchangeable, and the direction people rarely check is this one: FDA has stated that 'Wegovy and Wegovy HD, the approved formulations that do not contain propylene glycol, have not been shown to be safe and effective for the treatment of type 2 diabetes.' FDA made that statement in its 503B notice while noting that the semaglutide products approved for subcutaneous injection — Ozempic, Wegovy and Wegovy HD — 'have differing concentrations and labeled indications'. So the non-interchangeability runs both ways: Ozempic carries no weight-management indication, and Wegovy carries no type 2 diabetes indication. Read the appositive in FDA's sentence too, because it is doing work — the formulations FDA is describing are the propylene-glycol-free ones, which is the same distinction the 'PG-free' compounding pitch turns on.", "source": { "url": "https://www.federalregister.gov/documents/2026/05/01/2026-08552/list-of-bulk-drug-substances-for-which-there-is-a-clinical-need-under-section-503b-of-the-federal", "title": "List of Bulk Drug Substances for Which There Is a Clinical Need Under Section 503B of the Federal Food, Drug, and Cosmetic Act", "publisher": "FDA", "date": "2026-05-01", "quote": "We note that the semaglutide drug products approved for use as an SC injection (i.e., Ozempic, Wegovy, Wegovy HD) have differing concentrations and labeled indications. Wegovy and Wegovy HD, the approved formulations that do not contain propylene glycol, have not been shown to be safe and effective for the treatment of type 2 diabetes." }, "verifiedAt": "2026-07-16" }, { "question": "Is semaglutide sold as a research peptide the same thing as Ozempic or Wegovy?", "answer": "No. FDA has warned companies that illegally sold unapproved drugs containing semaglutide, tirzepatide or retatrutide that were 'falsely labeled \"for research purposes\" or \"not for human consumption\"', noting that these products have been sold directly to consumers for human use with dosing instructions. Read FDA's verb: falsely labeled. FDA does not treat the research wording as a disclaimer that changes what the product is — it treats it as a false statement about it, and characterises the sale as illegal notwithstanding the wording on the vial. FDA's stated tell is the conduct: a product shipped to consumers with instructions for human use is not being sold for research. The approval, the labels and the outcome trials behind the approved products describe those products, and an unapproved vial sits outside all three.", "source": { "url": "https://www.fda.gov/drugs/drug-alerts-and-statements/fdas-concerns-unapproved-glp-1-drugs-used-weight-loss", "title": "FDA's Concerns with Unapproved GLP-1 Drugs Used for Weight Loss", "publisher": "FDA", "date": "2026-06-15", "quote": "FDA has warned companies that have illegally sold unapproved drugs containing semaglutide, tirzepatide or retatrutide that are falsely labeled \"for research purposes\" or \"not for human consumption.\" These products have been sold directly to consumers for human use with dosing instructions." }, "verifiedAt": "2026-07-16" }, { "question": "Is semaglutide sodium or semaglutide acetate the same drug as the approved semaglutide?", "answer": "No — FDA's position is that they are a DIFFERENT ACTIVE INGREDIENT, not a lower grade of the same one. FDA received reports that in some cases compounders may be using salt forms of semaglutide, including semaglutide sodium and semaglutide acetate, and stated: 'The salt forms are different active ingredients than is used in the approved drugs, which contain the base form of semaglutide. The FDA is not aware of any basis for compounding using the salt forms that would meet the FD&C Act conditions for types of active ingredients that can be used in compounding.' That distinction is what a vial labelled simply 'semaglutide' hides. If the contents are a salt form, the approval, the prescribing information and the outcome trials behind the approved products are not describing what is in the vial — those studied the base form. FDA has since restated the position in different words, saying it does 'not have information on whether these salts have the same chemical and pharmacologic properties as the active ingredient in the approved drug' and is 'not aware of any lawful basis for their use in compounding' — that later wording is on FDA's GLP-1 concerns page, not on the alert quoted here.", "source": { "url": "https://www.fda.gov/drugs/human-drug-compounding/fda-alerts-health-care-providers-compounders-and-patients-dosing-errors-associated-compounded", "title": "FDA alerts health care providers, compounders and patients of dosing errors associated with compounded injectable semaglutide products", "publisher": "FDA", "date": "2024-07-26", "quote": "FDA had also received reports that in some cases, compounders may be using salt forms of semaglutide, including semaglutide sodium and semaglutide acetate. The salt forms are different active ingredients than is used in the approved drugs, which contain the base form of semaglutide. The FDA is not aware of any basis for compounding using the salt forms that would meet the FD&C Act conditions for types of active ingredients that can be used in compounding." }, "verifiedAt": "2026-07-16" }, { "question": "Did FDA find that compounded semaglutide doesn't work?", "answer": "No — FDA never reached that question, and says so explicitly. FDA's clinical-need analysis under section 503B is sequential, and its evaluation of semaglutide stopped at the threshold: 'Because this nomination did not pass through Part 1(a), we did not reach Part 2 and therefore did not consider the Part 2 factors, including the available evidence of effectiveness or lack of effectiveness of a drug product compounded with semaglutide.' What FDA actually evaluated was narrow — whether the nominations identified an attribute of the FDA-approved semaglutide products that makes them medically unsuitable for identified patients, such that a compounded product is needed to address it. It found they did not, and on that basis tentatively found no clinical need and proposed not to include semaglutide on the 503B Bulks List. So FDA's proposal is not a verdict that compounded semaglutide is ineffective, and equally the absence of such a verdict is not evidence that it works. On this record FDA has expressed no view either way.", "source": { "url": "https://www.federalregister.gov/documents/2026/05/01/2026-08552/list-of-bulk-drug-substances-for-which-there-is-a-clinical-need-under-section-503b-of-the-federal", "title": "List of Bulk Drug Substances for Which There Is a Clinical Need Under Section 503B of the Federal Food, Drug, and Cosmetic Act", "publisher": "FDA", "date": "2026-05-01", "quote": "Because this nomination did not pass through Part 1(a), we did not reach Part 2 and therefore did not consider the Part 2 factors, including the available evidence of effectiveness or lack of effectiveness of a drug product compounded with semaglutide." }, "verifiedAt": "2026-07-16" }, { "question": "Is compounded semaglutide safe?", "answer": "Compounded semaglutide is not an FDA-approved drug, which means FDA does not review it for safety, effectiveness or quality before it is marketed, and FDA has published specific documented concerns about it. As of 31 May 2026 FDA had received 990 reports of adverse events associated with compounded semaglutide; FDA notes many of these appear consistent with adverse events seen with the approved products, that causation cannot always be determined, and that because federal law does not require non-outsourcing-facility pharmacies to report adverse events, the true number is likely underreported. Separately, FDA has received reports of adverse events, some requiring hospitalization, that may be related to overdoses from dosing errors with compounded injectable semaglutide, which it attributes to patients measuring and self-administering incorrect amounts and to health care professionals miscalculating — the approved products are pens delivering a preset amount, while compounded products are supplied as vials and syringes. FDA has also reported fraudulent compounded semaglutide whose labels name compounding pharmacies that do not exist. Note the shape of these findings: they concern the product and its presentation, not semaglutide the molecule, whose own labeled risks — including a boxed warning for thyroid C-cell tumors — apply regardless.", "source": { "url": "https://www.fda.gov/drugs/drug-alerts-and-statements/fdas-concerns-unapproved-glp-1-drugs-used-weight-loss", "title": "FDA's Concerns with Unapproved GLP-1 Drugs Used for Weight Loss", "publisher": "FDA", "date": "2026-06-15", "quote": "This can be risky for patients, as unapproved versions do not undergo FDA's review for safety, effectiveness and quality before they are marketed." }, "verifiedAt": "2026-07-16" } ] }, { "slug": "semax", "name": "Semax", "aliases": [ "Semax acetate", "Semax free base", "ACTH(4-10) analogue" ], "url": "https://peptides101.com/compounds/semax", "moleculeNote": "A synthetic heptapeptide analogue of the adrenocorticotropic hormone (ACTH) 4-10 fragment, sequence H-Met-Glu-His-Phe-Pro-Gly-Pro-OH. FDA evaluates two related substances: semax (free base) and semax acetate. These are different active pharmaceutical ingredients and hence different bulk drug substances. The distinction is not academic bookkeeping: FDA states the nominators' own packages were inconsistent about which one they were nominating, and that the clinical references 'do not specify whether the substance used was a free base or a salt'. Nobody — including FDA — can say with certainty which molecule the human data describes.", "quickAnswer": "Semax is not FDA-approved, is not a component of any FDA-approved drug, has no United States Pharmacopeia or National Formulary monograph, and appears nowhere on FDA's 503A bulk drug substances list — so it may not lawfully be used to compound a drug under section 503A of the Federal Food, Drug, and Cosmetic Act, for any indication; FDA staff proposed not adding semax (free base) or semax acetate to that list ahead of the Pharmacy Compounding Advisory Committee meeting on 23-24 July 2026. Semax is a registered drug in Russia and FDA counted several hundred documented human exposures, all intranasal, but FDA evaluated semax for cerebral ischemia, migraine and trigeminal neuralgia and found only two usable human references — one an open-label, uncontrolled study with no control group, the other a meeting abstract in an unknown number of subjects whose full article FDA could not locate — concluding that the evidence of effectiveness is insufficient and that those references demonstrated lack of effectiveness.", "fdaStatus": { "value": "not-approved", "note": "Not an FDA-approved drug for any indication, and not in active development toward approval. That says nothing about whether it is sold — it is.", "source": { "url": "https://www.fda.gov/media/193348/download", "title": "Semax-Related Bulk Drug Substances — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, July 23-24, 2026", "publisher": "FDA", "date": "2026-07-23" }, "verifiedAt": "2026-07-16" }, "compoundingStatus": { "value": "withdrawn-from-nomination", "note": "Absent from Categories 1, 2 and 3 in the list updated 2026-05-14 — verified by fetching and text-extracting the document directly. Category 2 contains exactly six substances (Cesium Chloride, Domperidone, Germanium Sesquioxide, Ibutamoren Mesylate, Kisspeptin-10, Quinacrine HCl for intrauterine administration) and semax is not among them. The two nominations — Wells Pharmacy Network (FDA-2015-N-3534-0284) and LDT Health Solutions (FDA-2018-N-2973-0002) — were WITHDRAWN by the nominators (withdrawal document IDs FDA-2015-N-3534-0484 and -0485). Withdrawal is not a legalisation event: semax did not enter Category 1, is not on the 503A bulks list, and remains non-compoundable. Note the unusual wrinkle — FDA continued evaluating semax 'at its discretion' AFTER the nominations were withdrawn, on its own initiative, and is taking it to PCAC anyway.", "source": { "url": "https://www.fda.gov/media/193348/download", "title": "Semax-Related Bulk Drug Substances — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, July 23-24, 2026", "publisher": "FDA", "date": "2026-07-23" }, "verifiedAt": "2026-07-16" }, "evidence": { "tier": "animal-or-in-vitro-only", "humanAdministrationChecked": true, "note": "Administration check run and PASSED — this is NOT an endogenous-biomarker artefact. Semax really was given to humans (intranasally; FDA found no literature at all for the subcutaneous route), and semax is a registered drug in Russia sold as 0.1% and 1% nasal drops. The tier is nevertheless assigned on design, not on exposure counts or on foreign registration. No human RCT is verifiable. The two human studies FDA actually evaluated were: (1) Cherkasova et al. 2002, a meeting abstract with no full published article locatable, in an unknown number of subjects with chronic ischemic brain disease, which did not discuss clinical function before or after; and (2) Koroleva et al. 1996 (Bull Exp Biol Med 122:1107-1109, doi:10.1007/BF02447659), open-label, no blinding, no control group, n=12 migraine and n=25 trigeminal neuralgia. Hold the two apart rather than averaging them: Koroleva is the one FDA describes as open-label and uncontrolled, and it is the only one whose sample size FDA gives. For Cherkasova, FDA reports NO design information at all — not a control arm, not blinding, not an N — so this record does not characterise its design either way, and an unknown number of subjects cannot be called small. Note also what the Cherkasova finding is and is not: FDA says the authors 'do not provide full results for these lab values, nor do they discuss clinical function before and after receiving semax'. That is a reporting gap, not a reported null result, and this record will not upgrade one into the other. The precise statement is: no human RCTs; the only human study whose design FDA describes was open-label and uncontrolled, and what the two references reported, FDA characterised as demonstrating lack of effectiveness. ON THE TIER, DELIBERATELY AND NOT BY DEFAULT: 'animal-or-in-vitro-only' is the enum's label for 'no human RCTs', which is exactly true here, and the explainer that renders beside the badge says so. The badge WORD understates the human record, and that is a real cost, but the alternative is worse in the direction that matters: 'promising-but-unproven' would render the word 'Promising' over a compound whose two evaluated references FDA said demonstrated LACK of effectiveness, and 'no-credible-evidence' would deny the animal literature FDA discusses at length. The closed enum has no tier for 'human data exists and it pointed the wrong way', so the tier is held at the one that is literally true and the precision is carried here rather than flattering the compound in a badge. If a tier is ever added for that case, this record is the one to move first. IMPORTANT GAP, STATED RATHER THAN PAPERED OVER: a Russian-language clinical literature on semax in stroke does exist and is real — e.g. Gusev et al. 2018 (Zh Nevrol Psikhiatr Im S S Korsakova 118(3.Vyp.2):61-68, doi:10.17116/jnevro20181183261-68), Gusev et al. 2005, Gusev et al. 1997, Shmyrev et al. 1998. We have NOT read these in full and therefore do not assert what they administered, what design they used, or what they found. FDA did not consider them either, but for a procedural reason rather than a scientific one — 21 CFR 10.20(c)(2) requires a verified English translation, and none was submitted. Vendor pages citing 'Gusev' as proof of a positive controlled stroke trial are citing a paper neither they nor we have verified.", "source": { "url": "https://www.fda.gov/media/193348/download", "title": "Semax-Related Bulk Drug Substances — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, July 23-24, 2026", "publisher": "FDA", "date": "2026-07-23", "quote": "The only ROA discussed in the literature was intranasal. ... semax has been administered to 33-47 healthy adults, 69 adults with medical conditions (including chronic ischemic brain disease, pain due to migraine and trigeminal neuralgia, and peptic ulcer), and 451 children with either depression or tics/Tourette Syndrome." }, "verifiedAt": "2026-07-16" }, "fdaApproval": null, "fdaFindings": [ { "finding": "FDA staff propose not adding semax (free base) or semax acetate to the 503A Bulks List, ahead of the Pharmacy Compounding Advisory Committee meeting on 23-24 July 2026.", "note": "A staff proposal is not a final determination. The briefing document states: 'The FDA will not issue a final determination on the issues at hand until input from the advisory committee process has been considered and all reviews have been finalized.'", "source": { "url": "https://www.fda.gov/media/193348/download", "title": "Semax-Related Bulk Drug Substances — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, July 23-24, 2026", "publisher": "FDA", "date": "2026-07-23", "quote": "Accordingly, we propose not adding semax (free base) or semax acetate to the 503A Bulks List." }, "verifiedAt": "2026-07-16" }, { "finding": "FDA concluded there is insufficient evidence of effectiveness to support the use of semax-related bulk drug substances as a treatment for cerebral ischemia, migraine and trigeminal neuralgia.", "note": "Those three indications are the whole evaluation, and none of them is what semax is sold for in the US. FDA declined to evaluate ADHD because 'supporting literature for this use was not found', and declined 'nootropic' as a standalone use because it has no ICD-10 code and no professional society treatment guidelines — folding it into cerebral ischemia instead. Separately, and regardless of which uses were evaluated: semax is not on the 503A bulks list, so it may not lawfully be used in 503A compounding for ANY use. That follows from its absence from the list itself, not from the scope of FDA's evaluation. The nootropic and ADHD markets rest on an evidentiary vacuum FDA could not find literature to fill, which cuts against those claims rather than leaving room for them.", "source": { "url": "https://www.fda.gov/media/193348/download", "title": "Semax-Related Bulk Drug Substances — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, July 23-24, 2026", "publisher": "FDA", "date": "2026-07-23", "quote": "We have insufficient evidence of effectiveness to support the use of semax-related BDSs as a treatment for cerebral ischemia, migraine and trigeminal neuralgia." }, "verifiedAt": "2026-07-16" }, { "finding": "The only reference FDA evaluated in cerebral ischemia (Cherkasova et al. 2002) is a professional society meeting abstract for which no full published article could be located. It reports an unknown number of human subjects with chronic ischemic brain disease who received intranasal semax, and FDA states the authors did not provide full results for the lab values they measured and did not discuss clinical function before and after receiving semax.", "note": "Recorded because this reference does double duty in FDA's document and the two jobs pull in opposite directions — it is one of only two references in the effectiveness evaluation, AND it is the sole basis for the bleeding-risk flag. Both loads rest on an abstract whose full article nobody, FDA included, could find. Note precisely what FDA does and does not say about its design: FDA gives no sample size, no control arm, no blinding, and no design detail of any kind. It cannot be called small, and it cannot be called uncontrolled — the information to say either does not exist. FDA also notes the authors 'do not specify if these labs were done in the animal or human subjects', because the abstract describes a study in which semax was given to both rats and humans. 'Do not discuss clinical function' is an absence of reporting, not a reported finding of no effect; the distinction is the difference between a study that looked and found nothing and a study that never said.", "source": { "url": "https://www.fda.gov/media/193348/download", "title": "Semax-Related Bulk Drug Substances — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, July 23-24, 2026", "publisher": "FDA", "date": "2026-07-23", "quote": "This reference was submitted by the nominators and is an abstract from a professional society meeting. No full published article could be located for this reference. ... An unknown number of human subjects with chronic ischemic brain disease received intranasal semax ... Although the authors measured labs related to blood clotting (such as plasmin, antithrombin III, and protein C), the authors do not provide full results for these lab values, nor do they discuss clinical function before and after receiving semax." }, "verifiedAt": "2026-07-16" }, { "finding": "In the only study FDA evaluated in trigeminal neuralgia (Koroleva et al. 1996, n=25 total, single intranasal dose, open-label and uncontrolled), FDA concluded that semax was not effective in resolving pain for the majority of subjects. In the 16 subjects with typical trigeminal neuralgia the authors reported no changes in pain characteristics, sensation or pain thresholds, and concluded that semax does not exhibit analgesic activity by itself.", "note": "Recorded because this is a negative finding from the nominator's OWN submitted reference — the nominators submitted a study whose authors concluded the drug did not work. The study split three ways, and the positive-looking arms are reported here in full rather than filtered. Trigeminal neuralgia (n=25) divided into 16 subjects with typical trigeminal neuralgia and 9 with dental plexalgia; in the dental plexalgia subgroup FDA reports that 'pain resolved in 6 subjects and 3 subjects reported a decrease in pain severity'. FDA immediately qualifies that: 'MPST results showed that overall, there was no reduction in frequency of pain attacks, duration of pain attacks, and differences in sensory characteristics of pain', and 'it appears that the authors assigned arbitrary units when they discussed their findings'. In the migraine arm (n=12), FDA notes 4 of 12 subjects (33%) reported cessation of headache pain, and concluded that 'semax was not effective in resolving headache pain for the majority of subjects with migraine'. FDA's listed limitations: small sample size, no blinding, no control group, no reporting of actual scores or standard deviations, and insufficient detail on design and conduct.", "source": { "url": "https://www.fda.gov/media/193348/download", "title": "Semax-Related Bulk Drug Substances — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, July 23-24, 2026", "publisher": "FDA", "date": "2026-07-23", "quote": "no significant changes in TSEP were observed after a single intranasal administration of semax. This observation indicates that semax does not exhibit analgesic activity by itself." }, "verifiedAt": "2026-07-16" }, { "finding": "FDA identified no pharmacokinetic studies in humans following exposure to semax (free base) or semax acetate via any route of administration, and no safety data at all for the subcutaneous route proposed in the nominations.", "note": "The route mismatch is the practical point. Every human reference FDA found used INTRANASAL semax. Semax is nonetheless marketed in the US as an injectable — FDA's own briefing document cites vendor and clinic pages selling it. The human exposure history that vendors invoke does not cover the route those same vendors sell.", "source": { "url": "https://www.fda.gov/media/193348/download", "title": "Semax-Related Bulk Drug Substances — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, July 23-24, 2026", "publisher": "FDA", "date": "2026-07-23", "quote": "We were not able to find pharmacokinetic studies in humans following exposure to semax (free base) or semax acetate via any ROA. There are no safety data for semax (free base) and semax acetate administered by the proposed SC ROA." }, "verifiedAt": "2026-07-16" }, { "finding": "FDA found that semax injection and intranasal products are widely marketed in the United States through health/wellness clinics, medical concierge services, functional and regenerative medicine clinics, and online retailers, for a list of conditions including anxiety, depression, ADHD, stroke, ALS, Parkinson's disease and Alzheimer's disease.", "note": "None of those marketed uses is supported by the evaluation. FDA evaluated three indications and found the evidence insufficient for all three; the Alzheimer's, ALS and Parkinson's claims were not supported by literature FDA could locate at all. FDA also notes it is unclear to what extent semax has actually been used in compounding.", "source": { "url": "https://www.fda.gov/media/193348/download", "title": "Semax-Related Bulk Drug Substances — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, July 23-24, 2026", "publisher": "FDA", "date": "2026-07-23" }, "verifiedAt": "2026-07-16" }, { "finding": "FDA states there is no United States Pharmacopeia or National Formulary drug substance monograph for semax (free base) or semax acetate, and that neither is a component of an FDA-approved drug.", "note": "This single sentence closes all three doors at once, which is why it is recorded verbatim rather than paraphrased. Section 503A permits compounding with a bulk drug substance only if it (a) has an applicable USP or NF monograph, (b) is a component of an FDA-approved drug, or (c) appears on the 503A bulks list. FDA says here that semax fails (a) and (b); the list itself establishes it fails (c). 'Not FDA-approved' understates it — semax is not an ingredient of any approved product either, so there is no approved article anywhere in the US drug supply from which to argue a lineage.", "source": { "url": "https://www.fda.gov/media/193348/download", "title": "Semax-Related Bulk Drug Substances — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, July 23-24, 2026", "publisher": "FDA", "date": "2026-07-23", "quote": "There is no applicable United States Pharmacopeia (USP) or National Formulary (NF) drug substance monograph for semax (free base) or semax acetate, and neither is a component of an FDA-approved drug." }, "verifiedAt": "2026-07-16" }, { "finding": "FDA concluded that both semax (free base) and semax acetate are not well-characterized from the physical and chemical characterization perspective, citing inconsistent naming conventions and missing quality-control data on impurities, aggregates, bacterial endotoxins and microbial bioburden.", "note": "FDA reached the same not-well-characterized conclusion separately for each of the two substances, in parallel subsections. The naming half of it is a documented patient-safety argument rather than pedantry: FDA states that it 'has encountered multiple salts, and derivatives, including different active moieties, sold commercially under the same common name', and that inconsistent naming 'represent[s] a safety risk for patients as they may be dosed with a different BDS than the physician ordered'. Semax is a common name, not a United States Adopted Name. FDA also notes that none of the US vendor websites it searched indicates whether the marketed product contains the free base, a salt, or an ester.", "source": { "url": "https://www.fda.gov/media/193348/download", "title": "Semax-Related Bulk Drug Substances — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, July 23-24, 2026", "publisher": "FDA", "date": "2026-07-23", "quote": "Semax acetate is considered not well-characterized from the physical and chemical characterization perspective because (1) inconsistent naming conventions that do not follow established chemical nomenclature standards (e.g., INN, IUPAC, USAN), and (2) certain critical characterization data specific to semax acetate (including impurities, aggregates, microbial bioburden and/or bacterial endotoxin) were not found in the publicly available scientific literature, and the CoAs provided, which were offered as evidence to establishing identity, purity, and impurity profiles of the substance, lacked specific tests (including impurities, aggregates, microbial and bacterial endotoxins)." }, "verifiedAt": "2026-07-16" }, { "finding": "FDA's overall effectiveness conclusion is not merely that evidence is absent: FDA stated that only two usable references existed, that both lacked sufficient detail on design and conduct, and that the available references demonstrated lack of effectiveness.", "note": "Note the distinction this record refuses to blur, because it cuts both ways. 'Insufficient evidence of effectiveness' and 'demonstrated lack of effectiveness' are different findings, and FDA made BOTH about semax in the same document — the first as the formal standard it applies, the second as a description of what the two studies actually reported. For most compounds in this library the honest statement is only the first. For semax it is both, which is a stronger negative than 'no data'. Against that, the counterweight is stated rather than buried: only two references reached FDA's evaluation at all, so 'demonstrated lack of effectiveness' describes two small uncontrolled studies, not a body of literature.", "source": { "url": "https://www.fda.gov/media/193348/download", "title": "Semax-Related Bulk Drug Substances — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, July 23-24, 2026", "publisher": "FDA", "date": "2026-07-23", "quote": "Only two available references were available with insufficient details on the design and conduct of the studies, and the available references demonstrated lack of effectiveness and were limited by small sample size and lack of information about some relevant clinical endpoints." }, "verifiedAt": "2026-07-16" }, { "finding": "FDA found no evidence that semax has actually been used in pharmacy compounding: no outsourcing facility has reported compounding semax-containing products since 2019, a search identified no pharmacies marketing them, the nominators submitted 38 articles of which none discussed a compounded semax formulation, and no studies were found in which semax was used as a compounded drug product.", "note": "Historical use in compounding is one of the four criteria FDA balances, and semax scores close to zero on it. The finding matters mainly because of what it implies about the US supply: FDA simultaneously found semax injection and nasal products 'widely marketed' through clinics and online retailers, while finding essentially no evidence of lawful compounding behind them. FDA does record one enforcement data point, citing a press release from the US Attorney for the Eastern District of Kentucky stating that a pharmacy compounded and distributed products containing semax between October 2018 and April 2020; FDA adds that it is unclear which form of semax was used. We have not read the underlying press release and do not characterise the charges beyond what FDA's document says.", "source": { "url": "https://www.fda.gov/media/193348/download", "title": "Semax-Related Bulk Drug Substances — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, July 23-24, 2026", "publisher": "FDA", "date": "2026-07-23", "quote": "No outsourcing facility has reported compounding drug products containing semax since 2019. ... A Google search did not identify any pharmacies that market drug products containing any form of semax. ... No studies were found in which semax was used as a compounded drug product." }, "verifiedAt": "2026-07-16" } ], "safetySignals": [ { "signal": "FDA concluded there is insufficient clinical information to characterize the safety profile of semax (free base) or semax acetate, and that use of semax-related bulk drug substances in compounding may raise safety concerns.", "note": "Read this against the exposure count rather than instead of it. Several hundred documented human exposures coexist with an uncharacterised safety profile, because most of the references simply did not discuss safety: FDA notes one reference reported no adverse events (Koroleva et al. 1996) and the remainder did not discuss adverse events at all. Three of the references are meeting abstracts whose full studies were unavailable — including all of the paediatric data. Absence of reported harm in studies that never looked for harm is not a safety finding.", "source": { "url": "https://www.fda.gov/media/193348/download", "title": "Semax-Related Bulk Drug Substances — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, July 23-24, 2026", "publisher": "FDA", "date": "2026-07-23", "quote": "There is insufficient clinical information to characterize the safety profile of semax (free base) or semax acetate." }, "verifiedAt": "2026-07-16" }, { "signal": "FDA flagged a possible bleeding risk: one reference discussed possible anti-thrombotic properties of semax, raising concern particularly for populations at risk for bleeding or for people taking other medications that increase bleeding risk.", "note": "The labeling half of that quote is the part that carries the weight. FDA's objection is not only that a bleeding signal exists but that compounded drugs 'do not include labeling that would adequately warn physicians and patients of such risks' — so the warning that would let someone on an anticoagulant avoid the interaction is structurally absent from the product. Note also the thinness of the underlying signal: it rests on a single reference (Cherkasova et al. 2002), which is itself the meeting abstract whose full article we could not locate. A possible risk flagged from an unverifiable abstract is not a quantified risk, and it is not reassurance either.", "source": { "url": "https://www.fda.gov/media/193348/download", "title": "Semax-Related Bulk Drug Substances — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, July 23-24, 2026", "publisher": "FDA", "date": "2026-07-23", "quote": "One reference (Cherkasova et al. 2002) discussed possible anti-thrombotic properties of semax and this raises concern about the risk of bleeding, particularly in certain populations at risk for bleeding or if combined with other medications that increase bleeding risk. Compounded drugs do not include labeling that would adequately warn physicians and patients of such risks." }, "verifiedAt": "2026-07-16" }, { "signal": "FDA identified no clinical studies assessing immunogenicity or aggregation of semax (free base) or semax acetate, and concluded available information is insufficient to conclude that the substances do not present these risks.", "note": "FDA's concern is specific to the injection route proposed in the nominations, on the basis that peptides have an inherent tendency to aggregate and that aggregation is a risk factor for immunogenicity. FDA notes peptides with as few as two amino acids have been shown to aggregate, so semax's small size (seven amino acids) is not a defence.", "source": { "url": "https://www.fda.gov/media/193348/download", "title": "Semax-Related Bulk Drug Substances — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, July 23-24, 2026", "publisher": "FDA", "date": "2026-07-23" }, "verifiedAt": "2026-07-16" }, { "signal": "FDA identified quality and manufacturing gaps in the withdrawn nominations: no information on the nature of individual impurities permitted at up to 1.0% and 2.0% levels, no water solubility data, no microbial bioburden testing result, and a lack of endotoxin data for injectable routes of administration.", "note": "Sourced from FDA's review of the certificates of analysis the two withdrawn nominators supplied — i.e. the best documentation the nominating side chose to put forward. FDA states the impurity information 'also cannot be found from publicly available' sources. FDA also found no information on how an appropriate container and pump for an intranasal spray product would be selected and qualified.", "source": { "url": "https://www.fda.gov/media/193348/download", "title": "Semax-Related Bulk Drug Substances — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, July 23-24, 2026", "publisher": "FDA", "date": "2026-07-23" }, "verifiedAt": "2026-07-16" }, { "signal": "FDA's search of the FAERS adverse event database through 3 December 2025 retrieved one report (#25343150): a consumer reported ocular pain and eye burning after using semax 0.1% nasal drops purchased online, reported hospitalization following the exposure, and reported that the eye pain had not resolved a year later.", "note": "One report is one report, and it is worth stating precisely what it is and is not. It is a direct consumer report, not an investigated case: FDA does not adjudicate causation, the product was bought online rather than dispensed, and its actual contents were never verified. FAERS is a passive system and cannot support a rate. What makes it worth recording is the structural point FDA attaches in a footnote — compounders under section 503A generally do not report adverse events to FDA, so 'unless an adverse event report is submitted to FDA, the Agency may not be aware of adverse events associated with a product compounded under section 503A'. A near-empty FAERS record for a widely marketed compound is evidence about the reporting system, not evidence about the compound. FDA's two literature searches identified no published case reports of adverse events in humans.", "source": { "url": "https://www.fda.gov/media/193348/download", "title": "Semax-Related Bulk Drug Substances — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, July 23-24, 2026", "publisher": "FDA", "date": "2026-07-23" }, "verifiedAt": "2026-07-16" }, { "signal": "FDA identified no acute toxicity, repeat-dose toxicity, genotoxicity, or developmental and reproductive toxicity studies of semax, and no adequate carcinogenicity assessment.", "note": "This is the nonclinical floor, and semax is below it on every rung: FDA records separately, for each study type, that 'the nominator did not submit, and FDA did not identify' such studies. The single carcinogenicity-adjacent study FDA found (Meshavkin et al. 2013, in tumour-bearing female mice) FDA judged 'not adequately designed to assess the carcinogenic potential of semax', noting it tested one fixed level, used only females, and ran under three months against a standard of two years. Read this next to the exposure history rather than instead of it: several hundred people have received semax without the animal toxicology package that would normally precede a first-in-human study existing at all.", "source": { "url": "https://www.fda.gov/media/193348/download", "title": "Semax-Related Bulk Drug Substances — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, July 23-24, 2026", "publisher": "FDA", "date": "2026-07-23" }, "verifiedAt": "2026-07-16" }, { "signal": "FDA flagged an unassessed abuse potential: in mice, semax potentiated amphetamine-induced dopamine release in the striatum, which FDA called concerning because increased dopaminergic tone in the striatum is a response typically induced by drugs of abuse such as cocaine, and FDA identified no studies informing whether semax has reinforcing or addictive properties.", "note": "Recorded because it inverts the marketing. Semax is sold in the US partly for opioid withdrawal — FDA's own survey of vendor sites lists that use — and the one nonclinical signal FDA singled out as concerning points toward abuse liability rather than away from it. Hold the strength of the claim steady in both directions: this is a mouse finding about a drug interaction, FDA did not conclude that semax is abusable, and the honest statement is that the question was never studied. FDA carried the point up into its formal conclusion section, so it is not an aside in the text.", "source": { "url": "https://www.fda.gov/media/193348/download", "title": "Semax-Related Bulk Drug Substances — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, July 23-24, 2026", "publisher": "FDA", "date": "2026-07-23", "quote": "This finding is concerning because increased dopaminergic tone in the striatum is a response typically induced by drugs of abuse such as cocaine ... At the time of this evaluation, the nominator did not submit, and FDA did not identify nonclinical studies to demonstrate whether semax has reinforcing and addictive properties to inform its abuse potential." }, "verifiedAt": "2026-07-16" } ], "faqs": [ { "question": "Is Semax legal in the US in 2026?", "answer": "No. Semax appears in none of the three categories of FDA's 503A bulk drug substances list as updated 14 May 2026 — it is not on the list at all — so semax may not lawfully be used to compound a drug under section 503A of the Federal Food, Drug, and Cosmetic Act, for any indication and regardless of whether a prescriber writes for it. Absence from the list is the restriction itself, not a technicality that a prescription cures. Being off the list is a statement about the compounding pathway; what any individual state or federal enforcement action treats as a crime is a separate question this answer does not address.", "source": { "url": "https://www.fda.gov/media/94155/download", "title": "Bulk Drug Substances Nominated for Use in Compounding Under Section 503A of the Federal Food, Drug, and Cosmetic Act", "publisher": "FDA", "date": "2026-05-14" }, "verifiedAt": "2026-07-16" }, { "question": "Did Semax become legal when the FDA nominations for it were withdrawn?", "answer": "No. The two nominations to add semax to FDA's 503A bulks list were withdrawn by the nominators themselves, and a withdrawn nomination does not place a substance on the list — it removes the request, not the restriction. Semax's status moved sideways rather than toward legality: it never entered Category 1, it is absent from the 503A bulks list entirely, and it therefore remains outside lawful compounding under section 503A. FDA states that it is evaluating semax acetate and semax (free base) at its own discretion despite the withdrawals, and FDA staff went on to propose not adding either substance.", "source": { "url": "https://www.fda.gov/media/193348/download", "title": "Semax-Related Bulk Drug Substances — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, July 23-24, 2026", "publisher": "FDA", "date": "2026-07-23", "quote": "The nominations were withdrawn and FDA is evaluating the substances at its discretion." }, "verifiedAt": "2026-07-16" }, { "question": "Did FDA approve Semax?", "answer": "No. FDA has never approved semax, and FDA states that neither semax (free base) nor semax acetate is even a component of an FDA-approved drug, and that no United States Pharmacopeia or National Formulary drug substance monograph exists for either. Semax is a registered drug in Russia, sold there as 0.1% and 1% nasal drops, but a foreign registration is not an FDA approval and confers no United States legal status.", "source": { "url": "https://www.fda.gov/media/193348/download", "title": "Semax-Related Bulk Drug Substances — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, July 23-24, 2026", "publisher": "FDA", "date": "2026-07-23", "quote": "There is no applicable United States Pharmacopeia (USP) or National Formulary (NF) drug substance monograph for semax (free base) or semax acetate, and neither is a component of an FDA-approved drug. ... Semax is a registered drug in Russia and is available as 0.1% and 1% nasal drops." }, "verifiedAt": "2026-07-16" }, { "question": "Is there any human evidence that Semax works?", "answer": "No randomised controlled trial of semax in humans is verifiable in the English-language literature. FDA evaluated semax for cerebral ischemia, migraine and trigeminal neuralgia and found only two usable human references: a 2002 meeting abstract with no locatable full article, in an unknown number of subjects, which did not discuss clinical function before or after — a gap in what was reported, not a reported finding of no effect — and a 1996 study with no blinding and no control group. FDA concluded both that the evidence of effectiveness is insufficient for all three conditions and that the available references demonstrated lack of effectiveness. Professional society treatment guidelines for all three conditions do not discuss semax. Semax has been administered to several hundred people, but exposure is not efficacy. A Russian-language clinical literature on semax in stroke does exist; FDA did not consider it, because 21 CFR 10.20(c)(2) requires a verified English translation and none was submitted.", "source": { "url": "https://www.fda.gov/media/193348/download", "title": "Semax-Related Bulk Drug Substances — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, July 23-24, 2026", "publisher": "FDA", "date": "2026-07-23", "quote": "Only two available references were available with insufficient details on the design and conduct of the studies, and the available references demonstrated lack of effectiveness and were limited by small sample size and lack of information about some relevant clinical endpoints." }, "verifiedAt": "2026-07-16" }, { "question": "Does Semax work as a nootropic or for ADHD?", "answer": "FDA evaluated neither use for semax, and said why in each case. FDA declined to evaluate semax for ADHD because supporting literature for that use was not found. FDA declined to treat 'nootropic' as a standalone use because it has no ICD-10 code and no professional society treatment guidelines could be found for it, folding it instead into the evaluation of cerebral ischemia — for which FDA concluded the evidence of effectiveness is insufficient. No human trial supporting a cognitive-enhancement claim for semax was identified anywhere in FDA's review, and semax may not lawfully be compounded in the US for these or any other uses, because it is not on FDA's 503A bulks list.", "source": { "url": "https://www.fda.gov/media/193348/download", "title": "Semax-Related Bulk Drug Substances — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, July 23-24, 2026", "publisher": "FDA", "date": "2026-07-23", "quote": "Semax was also nominated for “ADHD” and “nootropic”. ADHD was not evaluated because supporting literature for this use was not found. “Nootropic” does not have an ICD-10 code and no professional society treatment guidelines could be found for this use." }, "verifiedAt": "2026-07-16" }, { "question": "Can I get Semax from a compounding pharmacy?", "answer": "Not lawfully. Semax is not on FDA's 503A bulks list, has no USP or NF monograph, and is not a component of an FDA-approved drug, so no US pharmacy may lawfully compound it under section 503A. FDA also found little sign that lawful compounding is where the US supply comes from: no outsourcing facility has reported compounding semax-containing products since 2019, and FDA's own search identified no pharmacies marketing them. FDA nonetheless found semax injection and intranasal products widely marketed in the United States through health and wellness clinics, medical concierge services, functional and regenerative medicine clinics, and online retailers.", "source": { "url": "https://www.fda.gov/media/193348/download", "title": "Semax-Related Bulk Drug Substances — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, July 23-24, 2026", "publisher": "FDA", "date": "2026-07-23", "quote": "No outsourcing facility has reported compounding drug products containing semax since 2019. ... A Google search did not identify any pharmacies that market drug products containing any form of semax." }, "verifiedAt": "2026-07-16" }, { "question": "Is Semax safe?", "answer": "Nobody knows, including FDA, which concluded that there is insufficient clinical information to characterize the safety profile of semax (free base) or semax acetate, and that use of semax-related bulk drug substances in compounding may raise safety concerns. That is not a finding of safety and not a finding of harm — it is a finding that the data needed to answer the question does not exist. FDA identified no human pharmacokinetic study by any route, no safety data at all for the subcutaneous injection route that US vendors sell, no acute toxicity, repeat-dose toxicity, genotoxicity or developmental and reproductive toxicity studies, and no clinical studies of immunogenicity. FDA flagged a possible bleeding risk, on a thin basis it states plainly: one reference (Cherkasova et al. 2002) discussed possible anti-thrombotic properties of semax, and FDA writes that the direct evidence of anticoagulant and antithrombotic properties comes from studies in non-ischemic rats. That reference is itself the meeting abstract whose full article could not be located. FDA notes compounded drugs carry no labeling that would warn physicians and patients of such a risk — so someone taking an anticoagulant gets no warning either way. Several hundred people have received semax, but most of the studies never looked for adverse events, and absence of reported harm in studies that did not look is not a safety finding.", "source": { "url": "https://www.fda.gov/media/193348/download", "title": "Semax-Related Bulk Drug Substances — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, July 23-24, 2026", "publisher": "FDA", "date": "2026-07-23", "quote": "There is insufficient clinical information to characterize the safety profile of semax (free base) or semax acetate. ... One reference (Cherkasova et al. 2002) discussed possible anti-thrombotic properties of semax and this raises concern about the risk of bleeding, particularly in certain populations at risk for bleeding or if combined with other medications that increase bleeding risk. ... Direct evidence that semax has anticoagulant and antithrombotic properties has been provided by studies conducted in non-ischemic rats." }, "verifiedAt": "2026-07-16" } ] }, { "slug": "sermorelin", "name": "Sermorelin", "aliases": [ "Sermorelin acetate", "GEREF", "Geref Diagnostic", "GHRH(1-29)NH2", "GRF(1-29)NH2" ], "url": "https://peptides101.com/compounds/sermorelin", "moleculeNote": "Sermorelin is the synthetic, amidated 1-29 fragment of endogenous human growth hormone-releasing hormone (GHRH, 44 amino acids) — the shortest fragment retaining full GH-releasing activity. It is a SECRETAGOGUE: it stimulates the pituitary to release the body's own growth hormone, and is not growth hormone itself. Do not conflate it with full-length GHRH, with tesamorelin (a stabilised GHRH analogue approved for a different indication entirely — HIV-associated lipodystrophy), or with CJC-1295 and other long-acting GHRH analogues that have no approval of any kind. Vendor copy frequently treats these as interchangeable; FDA's approvals do not.", "quickAnswer": "Sermorelin is not an FDA-approved drug: FDA withdrew approval of both GEREF (sermorelin acetate) new drug applications effective 18 June 2009 at the sponsor EMD Serono's own request, and Drugs@FDA records every sermorelin product it lists as discontinued. The approval sermorelin once held was for the treatment of idiopathic growth hormone deficiency in children with growth failure — not for the muscle-growth and fat-loss uses it is sold for now, which FDA has never evaluated and which it cited as unapproved-new-drug violations in a December 2024 warning letter. FDA's 2013 determination that GEREF was 'not withdrawn from sale for reasons of safety or effectiveness' is a narrow administrative finding whose stated purpose is to let generic applications reference the discontinued drug; it is not a safety clearance and not a current approval.", "fdaStatus": { "value": "approval-withdrawn", "note": "Approved once; FDA has since withdrawn the approval. No approved product is marketed. This is not a safety finding, and it is emphatically not an endorsement.", "source": { "url": "https://www.govinfo.gov/content/pkg/FR-2013-03-04/pdf/2013-04827.pdf", "title": "Determination That GEREF (Sermorelin Acetate) Injection, 0.5 Milligrams Base/Vial and 1.0 Milligrams Base/Vial, and GEREF (Sermorelin Acetate) Injection, 0.05 Milligrams Base/Amp, Were Not Withdrawn From Sale for Reasons of Safety or Effectiveness (78 FR 14095, Docket No. FDA-2012-P-1071)", "publisher": "Federal Register", "date": "2013-03-04" }, "verifiedAt": "2026-07-16" }, "compoundingStatus": null, "evidence": { "tier": "proven-in-humans", "humanAdministrationChecked": true, "note": "WHY THIS SOURCE AND NOT THE PIVOTAL ONE: 'proven-in-humans' is defined as efficacy established by adequate, WELL-CONTROLLED trials, so the tier is keyed to the randomised trial (PMID 8329826), not to the larger Geref International Study Group publication (PMID 8772599), which is OPEN-LABEL AND UNCONTROLLED and cannot carry that bar on its own. The randomised trial assigned 43 prepubertal children (mean age 10.4 +/- 2.9 yr) to two GHRH(1-29)NH2 regimens or to growth hormone; researchers reported a height-velocity increase of 2 cm/yr or more in all but two children, comparable height velocity in the high-dose GHRH and GH arms, but an increase in height SDS for bone age in the GH arm ONLY. It is small, six months long, and published in a supplement — the tier rests on it TOGETHER WITH FDA's approval of NDA 20-443 for this indication, not on it alone. ADMINISTRATION CHECK: passed, and unusually so for this library. Unlike MOTS-c and TB-500 — whose apparent human trials all turn out to measure the ENDOGENOUS peptide as a biomarker — sermorelin was genuinely administered to human subjects in both trials. The supporting pivotal programme publication (Geref International Study Group, J Clin Endocrinol Metab 1996;81(3):1189-96, PMID 8772599, https://pubmed.ncbi.nlm.nih.gov/8772599/ — n=110 previously untreated prepubertal GH-deficient children, 86 eligible for efficacy analysis) administered once-daily subcutaneous sermorelin for up to one year; researchers reported mean height velocity rose from 4.1 +/- 0.9 cm/yr at baseline to 7.2 +/- 1.3 cm/yr at 12 months, and characterised the drug as well tolerated — but reported it without a control arm. THE TIER IS SCOPED TO ONE INDICATION AND DOES NOT TRAVEL: 'proven-in-humans' here means FDA found substantial evidence of effectiveness for GROWTH FAILURE IN CHILDREN WITH IDIOPATHIC GH DEFICIENCY, and nothing else. Limitations, stated plainly: only 74% of children were rated good responders at 6 months in the pivotal study. The non-response is not a footnote — in a follow-up cohort (PMID 11572326), 27 children who had withdrawn from Geref (25 of them for inadequate height velocity, one for injection site reactions) went on to respond excellently to recombinant growth hormone; in another multicentre study (PMID 7735367), 31.3% were poor responders and were switched to recombinant hGH. The pattern across these reports is that a secretagogue depends on a pituitary that can still answer, and in a meaningful minority of these children the investigators reported that it did not. FOR THE MARKETED USE THERE IS NO SUCH EVIDENCE: we searched PubMed on 2026-07-16 for sermorelin administered to healthy adults for aging, body composition or longevity endpoints and found no adequate and well-controlled trial. What that search returns is a narrative review, an editorial, and animal studies of GHRH ANTAGONISTS — a different class of molecule with the opposite pharmacology. FDA never evaluated sermorelin for any adult anti-aging use.", "source": { "url": "https://pubmed.ncbi.nlm.nih.gov/8329826/", "title": "Growth response to growth hormone-releasing hormone(1-29)-NH2 compared with growth hormone. Neyzi O, Yordam N, Ocal G, et al. Acta Paediatr Suppl 1993;388:101-6", "publisher": "PubMed", "date": "1993-01-01" }, "verifiedAt": "2026-07-16" }, "fdaApproval": { "applicationNumber": "NDA 020443", "brandName": "GEREF", "approvedIndication": "indicated for the treatment of idiopathic growth hormone deficiency (GHD) in children with growth failure", "discontinued": true, "discontinuedNote": "Discontinued, and explicitly NOT for safety or efficacy reasons — but read what that determination actually says before it gets recycled as an endorsement. EMD Serono notified FDA by letter dated 2008-12-02 that GEREF injection (0.5 mg base/vial and 1.0 mg base/vial) was being discontinued and requested withdrawal of NDA 20-443; FDA withdrew approval effective 2009-06-18. Responding to a citizen petition (Docket No. FDA-2012-P-1071), FDA determined under 21 CFR 314.161 that the product 'w[as] not withdrawn for reasons of safety or effectiveness', having reviewed its own files and independently evaluated relevant literature and postmarketing adverse event data. The product stays on the Orange Book's Discontinued Drug Product List, which 'delineates, among other items, drug products that have been discontinued from marketing for reasons other than safety or effectiveness'. THE PURPOSE of that determination is narrow and administrative: it lets FDA approve ANDAs referencing GEREF. It is a finding about why a company stopped selling a drug — a commercial decision — NOT a safety clearance, NOT a current approval, and NOT any statement that sermorelin works for aging, body composition or 'GH optimisation'. Marketing that cites this determination as proof sermorelin is 'FDA-vetted and safe' is inverting it.", "source": { "url": "https://www.govinfo.gov/content/pkg/FR-2013-03-04/pdf/2013-04827.pdf", "title": "Determination That GEREF (Sermorelin Acetate) Injection, 0.5 Milligrams Base/Vial and 1.0 Milligrams Base/Vial, and GEREF (Sermorelin Acetate) Injection, 0.05 Milligrams Base/Amp, Were Not Withdrawn From Sale for Reasons of Safety or Effectiveness (78 FR 14095, Docket No. FDA-2012-P-1071)", "publisher": "Federal Register", "date": "2013-03-04" }, "verifiedAt": "2026-07-16" }, "fdaFindings": [ { "finding": "FDA withdrew approval of both GEREF (sermorelin acetate) new drug applications effective June 18, 2009, acting on EMD Serono's own written request after the company informed FDA the products were no longer marketed and waived its opportunity for a hearing.", "note": "THIS IS THE DOCUMENT THAT ENDED THE APPROVAL, and it is the one the market never reads — which is why 'sermorelin is an FDA-approved peptide' survives in 2026. The operative sentence is unambiguous: under section 505(e) of the FD&C Act, 'approval of the applications listed in the table in this document, and all amendments and supplements thereto, is hereby withdrawn, effective June 18, 2009.' Note what the quoted passage establishes and what it does not. The withdrawal was APPLICANT-INITIATED — a company electing to stop marketing a drug and asking FDA to close the file — so it is not a safety action, and this record does not present it as one. But 'not a safety action' does not soften the legal consequence: a withdrawn approval is not a dormant approval. There is no approved application in effect, and there has not been since 2009.", "source": { "url": "https://www.govinfo.gov/content/pkg/FR-2009-05-19/pdf/E9-11628.pdf", "title": "Novartis Pharmaceuticals Corp. et al.; Withdrawal of Approval of 92 New Drug Applications and 49 Abbreviated New Drug Applications (74 FR 23407, FR Doc. E9-11628)", "publisher": "Federal Register", "date": "2009-05-19", "quote": "The holders of the applications listed in the table in this document have informed FDA that these drug products are no longer marketed and have requested that FDA withdraw approval of the applications. The applicants have also, by their requests, waived their opportunity for a hearing." }, "verifiedAt": "2026-07-16" }, { "finding": "FDA stated in December 2024 that no FDA-approved application under section 505 is in effect for the sermorelin product it reviewed.", "note": "The single most useful sentence in this record for the question people actually ask. It is FDA, in the present tense, in 2024 — fifteen years after the withdrawal and eleven after the 2013 determination — confirming that no approval is in effect for a sermorelin product being sold. Anyone can claim the 2009 withdrawal left some residue of approval behind; this is FDA saying it did not. The sentence is scoped to the seven products in this letter, SERMORELIN among them, and we do not stretch it further than that.", "source": { "url": "https://www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/warning-letters/xcel-research-llc-694608-12102024", "title": "Warning Letter — Xcel Research LLC (694608)", "publisher": "FDA", "date": "2024-12-10", "quote": "No FDA-approved applications pursuant to section 505 of the FD&C Act, 21 U.S.C. 355, are in effect for these products." }, "verifiedAt": "2026-07-16" }, { "finding": "FDA held that 'FOR RESEARCH USE ONLY' and 'NOT INTENDED FOR HUMAN USE' labelling did not prevent a sermorelin product from being a drug intended for human use, because the seller's own website content established the human intended use.", "note": "Recorded verbatim because this is a FAILED legal theory, and it is reproduced here as a failed one. The disclaimer is the load-bearing element of nearly every research-peptide storefront selling sermorelin, and FDA disposed of it in one sentence: intended use is established by the evidence, and the seller's own marketing copy is that evidence. What the disclaimer bought Xcel Research was nothing at all.", "source": { "url": "https://www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/warning-letters/xcel-research-llc-694608-12102024", "title": "Warning Letter — Xcel Research LLC (694608)", "publisher": "FDA", "date": "2024-12-10", "quote": "Despite statements on your product labeling marketing your products, “FOR RESEARCH USE ONLY” and “NOT INTENDED FOR HUMAN USE,” evidence obtained from your website establishes that your products are intended to be drugs for human use." }, "verifiedAt": "2026-07-16" }, { "finding": "FDA found that sermorelin offered for sale online is an unapproved new drug, and that a 'FOR RESEARCH USE ONLY / NOT INTENDED FOR HUMAN USE' label does not cure the violation where site content establishes human intended use.", "note": "READ THE QUOTE AGAIN — IT IS THE VIOLATION, NOT THE DEFENCE. FDA reviewed xcelpeptides.com in October 2024 and reproduced all three of those bullets — verbatim, in the letter, under the heading '“SERMORELIN”' — as the evidence of intended use. THOSE THREE ARE THE COMPLETE SET: metabolism and weight loss, muscle growth and repair, metabolism and fat loss. FDA cited NO anti-aging claim for sermorelin in this letter; the words 'aging' and 'anti-aging' appear nowhere in it (we searched the full text on 2026-07-16 — the only hits are inside the word 'managing'). Sermorelin is marketed for anti-aging elsewhere, and this record says so in prose, but THIS letter is not the source for that and must not be cited as if it were. Note how carefully hedged the vendor copy is — 'studied in clinical trials', 'is believed to', 'in subjects', 'potential benefits'. The literature-review voice, the passive framing and the research-only disclaimer bought nothing: FDA held the products 'are not generally recognized as safe and effective for the above referenced uses and, therefore, are \"new drugs\" under section 201(p)', unlawful to introduce into interstate commerce under sections 505(a) and 301(d). BE PRECISE ABOUT WHAT THIS LETTER DOES NOT SAY: it makes no misbranding charge. We searched the full text on 2026-07-16 — 'misbrand', '502(f)' and 'adequate directions for use' each appear zero times, and the conclusion recites only 301(d) and 505(a). The charge is unapproved new drug, and nothing more. Sermorelin was cited alongside retatrutide, cagrilintide, mazdutide, semaglutide and survodutide in the same letter. This is also why the citations in the evidence field above are attributed to STUDIES and RESEARCHERS, never framed as what sermorelin can do for a reader.", "source": { "url": "https://www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/warning-letters/xcel-research-llc-694608-12102024", "title": "Warning Letter — Xcel Research LLC (694608)", "publisher": "FDA", "date": "2024-12-10", "quote": "Sermorelin, a peptide studied in clinical trials, is believed to enhance the release of growth hormone in subjects. This heightened growth hormone production is associated with potential benefits, including improved metabolism and the facilitation of weight loss. ... Enhanced Muscle Growth and Repair[.] One of the primary benefits observed in test subjects administered with sermorelin is enhanced muscle growth and repair. ... Improved Metabolism and Fat Loss[.] Another notable benefit of sermorelin is its potential to improve metabolism and aid in fat loss." }, "verifiedAt": "2026-07-16" }, { "finding": "Sermorelin does not appear in Category 1, Category 2 or Category 3 of FDA's 503A bulk drug substances nomination list as updated 2026-05-14.", "note": "Recorded as an observation, not a conclusion. Category 2 on that list contains exactly six substances — Cesium Chloride, Domperidone, Germanium Sesquioxide, Ibutamoren Mesylate, Kisspeptin-10, and Quinacrine Hydrochloride for intrauterine administration — and sermorelin is not among them, nor in Categories 1 or 3. Absence from this list is NOT a permission and NOT a safety finding, and it is a different situation from the withdrawn nominations (BPC-157, TB-500, semax and the rest). Any claim that sermorelin is 'compoundable' or 'exempt' requires an affirmative statutory basis that this record does not assert, because none of the primary documents we read establishes one.", "source": { "url": "https://www.fda.gov/media/94155/download", "title": "Bulk Drug Substances Nominated for Use in Compounding Under Section 503A of the Federal Food, Drug, and Cosmetic Act", "publisher": "FDA", "date": "2026-05-14" }, "verifiedAt": "2026-07-16" }, { "finding": "FDA stated that the purpose of its 2013 'not withdrawn for safety or effectiveness' determination for GEREF is to allow abbreviated new drug applications referencing GEREF to be approved.", "note": "FDA STATING THE PURPOSE OF ITS OWN DETERMINATION, IN ITS OWN WORDS, IN THE SUMMARY PARAGRAPH — which is why this quote is worth more than any amount of our explaining. The determination is a generic-entry mechanism. It exists so that a would-be ANDA applicant has a listed drug to reference, and 21 CFR 314.161 requires FDA to make the finding before any such ANDA can be approved. That is the whole of it. It is not a review of sermorelin's safety in adults, not a re-approval, not an endorsement, and not a statement about any product sold today. Marketing that presents 'FDA determined sermorelin was not withdrawn for safety reasons' as a safety credential is quoting a procedural step in a generic-drug pathway and calling it a clean bill of health. Note also the condition FDA attaches even to that narrow purpose: 'if all other legal and regulatory requirements are met' — the determination clears one procedural obstacle, it does not approve anything. WHETHER ANY ANDA EVER FOLLOWED is answered by Drugs@FDA itself, and the answer is that the generic entry this determination was designed to enable does not appear to have happened: the database lists exactly two sermorelin applications, both of them the original EMD Serono NDAs, and no ANDA (see the Drugs@FDA finding below).", "source": { "url": "https://www.govinfo.gov/content/pkg/FR-2013-03-04/pdf/2013-04827.pdf", "title": "Determination That GEREF (Sermorelin Acetate) Injection, 0.5 Milligrams Base/Vial and 1.0 Milligrams Base/Vial, and GEREF (Sermorelin Acetate) Injection, 0.05 Milligrams Base/Amp, Were Not Withdrawn From Sale for Reasons of Safety or Effectiveness (78 FR 14095, Docket No. FDA-2012-P-1071)", "publisher": "Federal Register", "date": "2013-03-04", "quote": "This determination will allow FDA to approve abbreviated new drug applications (ANDAs) for GEREF (Sermorelin Acetate) injection, 0.5 mg base/vial and 1.0 mg base/vial, and GEREF (Sermorelin Acetate) injection, 0.05 mg base/amp, if all other legal and regulatory requirements are met." }, "verifiedAt": "2026-07-16" }, { "finding": "Drugs@FDA lists exactly two applications containing sermorelin acetate — NDA 019863 and NDA 020443, both held by EMD Serono — and records every product under both as Discontinued. No abbreviated new drug application containing sermorelin acetate appears.", "note": "THE AFFIRMATIVE VERSION OF THE CLAIM EVERYONE MAKES BY INFERENCE. 'No approved sermorelin is sold in the US' is usually asserted from a failed search, which proves nothing. This is the database saying it: sermorelin IS listed, the listings ARE the two GEREF NDAs, and every product under both reads Discontinued. Nothing here rests on something not being found. READ THE MARKETING STATUS PRECISELY: 'Discontinued' is Drugs@FDA's marketing-status vocabulary and it describes the PRODUCT, not the application. It is the withdrawal notice (fdaFindings[0]) that ended the approvals and the December 2024 warning letter (fdaFindings[1]) that states no section 505 application is in effect — this finding corroborates those two, it does not carry the legal conclusion by itself. ON THE ANDA QUESTION: the query is by ACTIVE INGREDIENT, not by brand, so a generic sermorelin would be returned by it. Two records come back and both are NDAs. That is a real answer to the question fdaFindings[4] raises — the 2013 determination exists to let ANDAs reference GEREF, and thirteen years on, none appears to have. SCOPE, HONESTLY: Drugs@FDA covers FDA-approved applications. It says nothing whatever about the unapproved research-peptide market, where sermorelin is actually sold — that product was never in this database and its absence from it is not a finding about it.", "source": { "url": "https://api.fda.gov/drug/drugsfda.json?search=products.active_ingredients.name:%22SERMORELIN+ACETATE%22&limit=10", "title": "Drugs@FDA — applications containing SERMORELIN ACETATE (openFDA drug/drugsfda endpoint, 2 results: NDA019863, NDA020443)", "publisher": "FDA", "date": "2026-07-15", "quote": "\"application_number\": \"NDA019863\", \"sponsor_name\": \"EMD SERONO\" ... \"brand_name\": \"GEREF\", \"marketing_status\": \"Discontinued\" ... \"application_number\": \"NDA020443\", \"sponsor_name\": \"EMD SERONO INC\" ... \"brand_name\": \"GEREF\", \"marketing_status\": \"Discontinued\"" }, "verifiedAt": "2026-07-16" }, { "finding": "FDA recorded that the citizen petitioner identified no data or other information suggesting either GEREF product was withdrawn for reasons of safety or effectiveness.", "note": "Kept because it shows the SHAPE of the determination, which is the thing most often misread. FDA is describing an absence in a petition record, and the petition was filed by Alvin J. Lorman on 2012-10-12 (Docket No. FDA-2012-P-1071) asking FDA to make exactly this finding — the posture is a party seeking a generic-entry ruling and FDA agreeing nobody produced contrary evidence. An absence of adverse data in a 2012 petition about a drug that left the US market in 2009 is a thin thing to build a safety claim on, and the determination never claims otherwise. FDA did also review its own files and the literature independently (see safetySignals) — but the standard it applied throughout is 'was this withdrawn FOR safety reasons', not 'is this safe'. Those are different questions and only the first one was asked.", "source": { "url": "https://www.govinfo.gov/content/pkg/FR-2013-03-04/pdf/2013-04827.pdf", "title": "Determination That GEREF (Sermorelin Acetate) Injection, 0.5 Milligrams Base/Vial and 1.0 Milligrams Base/Vial, and GEREF (Sermorelin Acetate) Injection, 0.05 Milligrams Base/Amp, Were Not Withdrawn From Sale for Reasons of Safety or Effectiveness (78 FR 14095, Docket No. FDA-2012-P-1071)", "publisher": "Federal Register", "date": "2013-03-04", "quote": "The petitioner has identified no data or other information suggesting that GEREF (Sermorelin Acetate) injection, 0.5 mg base/vial and 1.0 mg base/vial, and GEREF (Sermorelin Acetate) injection, 0.05 mg base/amp, were withdrawn for reasons of safety or effectiveness." }, "verifiedAt": "2026-07-16" } ], "safetySignals": [ { "signal": "Injection site reactions occurred in the Geref paediatric programme and were sufficient to cause at least one child to withdraw from treatment.", "note": "Reported among 27 children who left a Geref trial — 25 withdrew for inadequate height velocity, one at the onset of puberty, and one for injection site reactions. Scope honestly: this is a small tolerability signal from a paediatric GHD population studied for months to a couple of years. It says nothing about the safety of unapproved research-grade sermorelin, of unknown identity and purity, self-administered by adults indefinitely — a setting for which we found no controlled safety data at all.", "source": { "url": "https://pubmed.ncbi.nlm.nih.gov/11572326/", "title": "Outcome of growth hormone therapy in children with growth hormone deficiency showing an inadequate response to growth hormone-releasing hormone. Endocrine 2001", "publisher": "PubMed", "date": "2001-08-01" }, "verifiedAt": "2026-07-16" }, { "signal": "FDA reviewed its files and independently evaluated relevant literature and possible postmarketing adverse events for both GEREF products, and identified no safety or effectiveness basis for their withdrawal from sale.", "note": "The absence of a signal is not the presence of safety, and this is the sentence most likely to be quoted out of context. FDA's review was bounded by what GEREF actually was: a prescription drug, manufactured to NDA standards, used in children with diagnosed GH deficiency under medical supervision, and off the US market since 2009. It was not an evaluation of long-term adult use, of anti-aging use, or of any product sold today. A favourable 2013 determination about a discontinued brand-name drug says nothing about a product that is not that drug.", "source": { "url": "https://www.govinfo.gov/content/pkg/FR-2013-03-04/pdf/2013-04827.pdf", "title": "Determination That GEREF (Sermorelin Acetate) Injection, 0.5 Milligrams Base/Vial and 1.0 Milligrams Base/Vial, and GEREF (Sermorelin Acetate) Injection, 0.05 Milligrams Base/Amp, Were Not Withdrawn From Sale for Reasons of Safety or Effectiveness (78 FR 14095, Docket No. FDA-2012-P-1071)", "publisher": "Federal Register", "date": "2013-03-04", "quote": "We have also independently evaluated relevant literature and data for possible postmarketing adverse events for both GEREF products. We have reviewed the available evidence and determined that both GEREF products were not withdrawn from sale for reasons of safety or effectiveness." }, "verifiedAt": "2026-07-16" } ], "faqs": [ { "question": "Is sermorelin FDA-approved?", "answer": "No. Sermorelin was approved, and is not now. FDA approved two GEREF (sermorelin acetate) new drug applications held by EMD Serono — NDA 19-863 on 28 December 1990 and NDA 20-443 on 26 September 1997 — and withdrew approval of both effective 18 June 2009, after EMD Serono informed FDA the products were no longer marketed and requested the withdrawal itself. In FDA's operative words, 'approval of the applications listed in the table in this document, and all amendments and supplements thereto, is hereby withdrawn, effective June 18, 2009.' No FDA-approved sermorelin product has been marketed in the United States since. FDA confirmed the point again in a December 2024 warning letter about a sermorelin product offered for sale online, stating that no FDA-approved applications under section 505 are in effect for those products. A drug that was approved in the past is not an approved drug.", "source": { "url": "https://www.govinfo.gov/content/pkg/FR-2009-05-19/pdf/E9-11628.pdf", "title": "Novartis Pharmaceuticals Corp. et al.; Withdrawal of Approval of 92 New Drug Applications and 49 Abbreviated New Drug Applications (74 FR 23407, FR Doc. E9-11628)", "publisher": "Federal Register", "date": "2009-05-19", "quote": "approval of the applications listed in the table in this document, and all amendments and supplements thereto, is hereby withdrawn, effective June 18, 2009." }, "verifiedAt": "2026-07-16" }, { "question": "Does 'not withdrawn for reasons of safety or effectiveness' mean FDA found sermorelin safe?", "answer": "No. That phrase is a finding about why a company stopped selling a drug, not a finding that the drug is safe, and FDA states its purpose plainly in the same notice: 'This determination will allow FDA to approve abbreviated new drug applications (ANDAs) for GEREF (Sermorelin Acetate) injection... if all other legal and regulatory requirements are met.' It is a generic-entry mechanism. Under 21 CFR 314.161 FDA must decide whether a discontinued drug left the market for safety or effectiveness reasons before it can approve any generic referencing it, and in 2013, responding to a citizen petition, FDA determined GEREF had not. That determination was bounded by what GEREF was: a prescription drug made to NDA standards, given to children with diagnosed growth hormone deficiency under medical supervision, and off the US market since 2009. It evaluated no adult use, no anti-aging use, and no product sold today, and it did not restore the approval, which remains withdrawn.", "source": { "url": "https://www.govinfo.gov/content/pkg/FR-2013-03-04/pdf/2013-04827.pdf", "title": "Determination That GEREF (Sermorelin Acetate) Injection, 0.5 Milligrams Base/Vial and 1.0 Milligrams Base/Vial, and GEREF (Sermorelin Acetate) Injection, 0.05 Milligrams Base/Amp, Were Not Withdrawn From Sale for Reasons of Safety or Effectiveness (78 FR 14095, Docket No. FDA-2012-P-1071)", "publisher": "Federal Register", "date": "2013-03-04", "quote": "This determination will allow FDA to approve abbreviated new drug applications (ANDAs) for GEREF (Sermorelin Acetate) injection, 0.5 mg base/vial and 1.0 mg base/vial, and GEREF (Sermorelin Acetate) injection, 0.05 mg base/amp, if all other legal and regulatory requirements are met." }, "verifiedAt": "2026-07-16" }, { "question": "Is there any human evidence that sermorelin works for anti-aging or building muscle?", "answer": "No adequate and well-controlled trial supports those uses, and FDA has never evaluated sermorelin for any of them. The human evidence for sermorelin is real but is confined to one population: children. FDA's approval of NDA 20-443 was for 'the treatment of idiopathic growth hormone deficiency (GHD) in children with growth failure', and the trials behind it enrolled prepubertal growth-hormone-deficient children and measured height velocity. A PubMed search on 16 July 2026 for sermorelin administered to healthy adults for aging, body-composition or longevity endpoints returned no adequate and well-controlled trial. When FDA reviewed a seller marketing sermorelin in October 2024 for 'enhanced muscle growth and repair' and 'improved metabolism and fat loss', it concluded the products 'are not generally recognized as safe and effective for the above referenced uses'. Evidence that a secretagogue raises growth hormone in children with a diagnosed deficiency is not evidence that it does anything for a healthy adult.", "source": { "url": "https://www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/warning-letters/xcel-research-llc-694608-12102024", "title": "Warning Letter — Xcel Research LLC (694608)", "publisher": "FDA", "date": "2024-12-10", "quote": "products are not generally recognized as safe and effective for the above referenced uses and, therefore, are “new drugs” under section 201(p) of the FD&C Act, 21 U.S.C. 321(p)." }, "verifiedAt": "2026-07-16" }, { "question": "Is it legal to buy sermorelin online in 2026?", "answer": "No. FDA has stated that sermorelin offered for sale online is an unapproved new drug whose introduction into interstate commerce is unlawful. In a warning letter dated 10 December 2024, FDA told Xcel Research LLC that its SERMORELIN product, alongside retatrutide, cagrilintide, mazdutide, semaglutide and survodutide, comprised 'unapproved new drugs introduced or delivered for introduction into interstate commerce in violation of sections 505(a) and 301(d)' of the Federal Food, Drug, and Cosmetic Act, and that no FDA-approved applications under section 505 are in effect for them. Labelling the vial 'FOR RESEARCH USE ONLY' and 'NOT INTENDED FOR HUMAN USE' did not change that result: FDA held that evidence from the seller's own website established the products were intended to be drugs for human use, regardless of the disclaimer. FDA's charge in that letter was the unapproved new drug violation; it brought no misbranding charge.", "source": { "url": "https://www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/warning-letters/xcel-research-llc-694608-12102024", "title": "Warning Letter — Xcel Research LLC (694608)", "publisher": "FDA", "date": "2024-12-10", "quote": "your “RETA” (Retatrutide), “CagriLean” (Cagrilintide and Semaglutide), “CAGRILINTIDE,” “MAZDUTIDE,” “SEMA” (Semaglutide), “SURVODUTIDE,” and “SERMORELIN,” products are unapproved new drugs introduced or delivered for introduction into interstate commerce in violation of sections 505(a) and 301(d) of the Federal Food, Drug, and Cosmetic Act (FD&C Act), 21 U.S.C. 355(a) and 331(d)." }, "verifiedAt": "2026-07-16" } ] }, { "slug": "setmelanotide", "name": "Setmelanotide", "aliases": [ "IMCIVREE", "Imcivree", "Setmelanotide acetate", "RM-493", "RM 493" ], "url": "https://peptides101.com/compounds/setmelanotide", "moleculeNote": "Per the FDA label's Description section, IMCIVREE contains setmelanotide acetate, described as a melanocortin 4 (MC4) receptor agonist and an 8 amino acid cyclic peptide analog of the endogenous melanocortin peptide alpha-MSH (alpha-melanocyte stimulating hormone), molecular formula C49H68N18O9S2 and molecular mass 1117.3 Daltons as the anhydrous free base. The approved product is a subcutaneous solution supplied at 10 mg/mL in a 1 mL multiple-dose vial. Read the receptor selectivity precisely, because it is the axis the wider melanocortin market turns on: the label's Mechanism of Action states setmelanotide is an MC4 receptor agonist 'with 20-fold less activity at the melanocortin 3 (MC3) and melanocortin 1 (MC1) receptors', and notes that MC1 receptors are expressed on melanocytes and that activating them leads to accumulation of melanin and increased skin pigmentation independently of ultraviolet light. Selective is not the same as silent — the pigmentation warning below is on the label of the selective compound.", "quickAnswer": "Setmelanotide is an FDA-approved melanocortin 4 (MC4) receptor agonist, marketed as IMCIVREE by Rhythm Pharmaceuticals under NDA 213793 and originally approved on 25 November 2020. The approved indication is narrow and diagnosis-gated: the FDA label indicates IMCIVREE to reduce excess body weight and maintain weight reduction long term in adults and pediatric patients aged 4 years and older with acquired hypothalamic obesity, and aged 2 years and older with Bardet-Biedl syndrome or with POMC, PCSK1 or leptin receptor (LEPR) deficiency confirmed by genetic testing. That same label's Limitations of Use state that IMCIVREE is not indicated for 'Other types of obesity not related to acquired HO, BBS, or POMC, PCSK1, or LEPR deficiency, including obesity associated with other genetic syndromes and general (polygenic) obesity', and its Pharmacodynamics section states that the safety and effectiveness of IMCIVREE have not been established in otherwise healthy patients with obesity and that IMCIVREE is not approved to treat such patients. The label carries warnings for disturbance in sexual arousal, depression and suicidal ideation, serious hypersensitivity reactions including anaphylaxis, and generalized skin hyperpigmentation with darkening of pre-existing nevi and development of new melanocytic nevi, for which it directs a full body skin examination before initiation and periodically during treatment.", "fdaStatus": { "value": "approved", "note": "FDA-approved and marketed. Drugs@FDA returns exactly one application for setmelanotide: NDA 213793, sponsor RHYTHM, brand name IMCIVREE, product 001 (setmelanotide acetate, solution, subcutaneous), marketing status 'Prescription'. The original submission was approved 25 November 2020 under priority review as a Type 1 New Molecular Entity, with an orphan submission property. Six supplements follow in the record, three of them efficacy supplements — SUPPL 1 approved 16 June 2022, SUPPL 7 approved 20 December 2024, and SUPPL 9 approved 19 March 2026 — every one of them priority-reviewed and carrying the orphan property. Approval is always for a specific indication and population, and here the population is defined by diagnosis and in part by genetic testing. Read the approval record below before treating this as an approved obesity drug in the general sense.", "source": { "url": "https://api.fda.gov/drug/drugsfda.json?search=openfda.generic_name:\"setmelanotide\"&limit=5", "title": "Drugs@FDA — approved drug products database, queried for setmelanotide (openFDA)", "publisher": "FDA", "date": "2026-07-31" }, "verifiedAt": "2026-08-02" }, "compoundingStatus": null, "evidence": { "tier": "proven-in-humans", "humanAdministrationChecked": true, "note": "Administration check RUN per registration on 2026-08-02, not inferred from the approval. The label names four pivotal trials and all four were opened on ClinicalTrials.gov. Every one lists lead sponsor Rhythm Pharmaceuticals, Inc., phase PHASE3, an intervention of type DRUG named 'Setmelanotide' alongside a DRUG placebo arm, an ACTUAL enrolment count, and hasResults true. Trial 1, NCT05774756 (acquired hypothalamic obesity): enrolment 143 ACTUAL, primary completion 2025-03-18 ACTUAL, status ACTIVE_NOT_RECRUITING. Trial 2, NCT03746522 (Bardet-Biedl syndrome): enrolment 52 ACTUAL, completed 2021-03-08. Trial 3, NCT02896192 (POMC/PCSK1 deficiency): enrolment 15 ACTUAL, completed 2020-05-25. Trial 4, NCT03287960 (LEPR deficiency): enrolment 15 ACTUAL, completed 2020-09-25. Setmelanotide was ADMINISTERED to human participants in each — this is not the endogenous biomarker trap that reduces MOTS-c and TB-500 from an apparent five human RCTs to an actual zero. None of these registrations shows the contamination seen elsewhere in this vertical: no cloned protocol, no recruiting shell, no empty results section. SCOPE, and it is the whole point of the tier being narrow. The tier attaches to the populations studied — acquired hypothalamic obesity, Bardet-Biedl syndrome, and POMC, PCSK1 or LEPR deficiency — and to nothing else. Trials 3 and 4 were open-label with an 8-week double-blind withdrawal period and analysed 21 patients between them; that is adequate for an orphan indication and is not a general obesity evidence base. The label itself states that safety and effectiveness have not been established in otherwise healthy patients with obesity. Evidence does not travel across indications.", "source": { "url": "https://clinicaltrials.gov/study/NCT05774756", "title": "A Trial of Setmelanotide in Acquired Hypothalamic Obesity", "publisher": "ClinicalTrials.gov", "date": "2025-03-18", "quote": "A Trial of Setmelanotide in Acquired Hypothalamic Obesity" }, "verifiedAt": "2026-08-02" }, "fdaApproval": { "applicationNumber": "NDA 213793", "brandName": "IMCIVREE", "approvedIndication": "IMCIVREE is indicated to reduce excess body weight and maintain weight reduction long term in adults and pediatric patients aged: 4 years and older with acquired hypothalamic obesity (HO); 2 years and older with syndromic or monogenic obesity due to: Bardet-Biedl syndrome (BBS); Pro-opiomelanocortin (POMC), proprotein convertase subtilisin/kexin type 1 (PCSK1), or leptin receptor (LEPR) deficiency confirmed by genetic testing demonstrating variants in POMC, PCSK1, or LEPR genes that are interpreted as pathogenic, likely pathogenic, or of uncertain significance (VUS). Limitations of Use: IMCIVREE is not indicated for the treatment of patients with the following conditions as IMCIVREE would not be expected to be effective: Obesity due to suspected POMC, PCSK1, or LEPR deficiency with POMC, PCSK1, or LEPR variants classified as benign or likely benign. Other types of obesity not related to acquired HO, BBS, or POMC, PCSK1, or LEPR deficiency, including obesity associated with other genetic syndromes and general (polygenic) obesity.", "discontinued": false, "source": { "url": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=70c3ccf7-4df0-4c75-ba07-fede9970c8d9", "title": "IMCIVREE (setmelanotide) injection, solution — Prescribing Information (current SPL)", "publisher": "DailyMed (U.S. National Library of Medicine)", "date": "2026-04-01", "quote": "IMCIVREE is a melanocortin 4 (MC4) receptor agonist indicated to reduce excess body weight and maintain reduction long term in adults and pediatric patients aged (1): 4 years and older with acquired hypothalamic obsesity (HO). 2 years and older with Bardet-Biedl syndrome (BBS). 2 years and older with pro-opiomelanocortin (POMC), proprotein convertase subtilisin/kexin type 1 (PCSK1), or leptin receptor (LEPR) deficiency …" }, "verifiedAt": "2026-08-02" }, "fdaFindings": [ { "finding": "The FDA-approved labeling for IMCIVREE states that it is not indicated for other types of obesity not related to acquired hypothalamic obesity, Bardet-Biedl syndrome, or POMC, PCSK1 or LEPR deficiency — including obesity associated with other genetic syndromes and general (polygenic) obesity — as it would not be expected to be effective.", "note": "The single most load-bearing sentence on this record. Note the wording of the exclusion: it is not a caution about unknown effects, it is a statement that the drug 'would not be expected to be effective' in these patients. The mechanism section explains why — the label describes setmelanotide as potentially re-establishing MC4 receptor pathway activity in patients whose obesity is 'associated with insufficient activation of the MC4 receptor'. Where that pathway defect is not the cause, the label does not expect the mechanism to apply. An MC4R agonist is not a general weight-loss drug on this label.", "source": { "url": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=70c3ccf7-4df0-4c75-ba07-fede9970c8d9", "title": "IMCIVREE (setmelanotide) injection, solution — Prescribing Information (current SPL)", "publisher": "DailyMed (U.S. National Library of Medicine)", "date": "2026-04-01", "quote": "Limitations of Use: IMCIVREE is not indicated for the treatment of patients with the following conditions as IMCIVREE would not be expected to be effective: • Obesity due to suspected POMC, PCSK1, or LEPR deficiency with POMC, PCSK1, or LEPR variants classified as benign or likely benign. • Other types of obesity not related to acquired HO, BBS, or POMC, PCSK1, or LEPR deficiency, including obesity associated with other genetic syndromes and general (polygenic) obesity." }, "verifiedAt": "2026-08-02" }, { "finding": "The label's Pharmacodynamics section reports that short-term administration of IMCIVREE in 12 otherwise healthy patients with obesity increased resting energy expenditure and shifted substrate oxidation to fat, and states in the same paragraph that the safety and effectiveness of IMCIVREE have not been established in such patients and that IMCIVREE is not approved to treat such patients.", "note": "An FDA label pre-emptively disclaiming the adjacent market, in one paragraph, on the same page as the finding that market would quote. The metabolic result is real and it is on the label; the sentence immediately after it is the reason the result cannot be carried into a general obesity or body-composition claim. Anyone citing the energy expenditure finding without the following sentence is quoting half of a two-sentence paragraph, and the half FDA wrote second is the one that scopes the first.", "source": { "url": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=70c3ccf7-4df0-4c75-ba07-fede9970c8d9", "title": "IMCIVREE (setmelanotide) injection, solution — Prescribing Information (current SPL)", "publisher": "DailyMed (U.S. National Library of Medicine)", "date": "2026-04-01", "quote": "Short-term administration of IMCIVREE in 12 otherwise healthy patients with obesity increased resting energy expenditure and shifted substrate oxidation to fat. The safety and effectiveness of IMCIVREE have not been established in such patients and IMCIVREE is not approved to treat such patients." }, "verifiedAt": "2026-08-02" }, { "finding": "Drugs@FDA records a single approved application containing setmelanotide — NDA 213793, sponsor RHYTHM, brand name IMCIVREE — originally approved 25 November 2020 under priority review as a Type 1 New Molecular Entity with an orphan submission property, with the most recent efficacy supplement (SUPPL 9) approved 19 March 2026.", "note": "Queried live on 2026-08-02 against openFDA `drug/drugsfda`, meta.last_updated 2026-07-31. One application, one product: product 001, active ingredient SETMELANOTIDE ACETATE, dosage form SOLUTION, route SUBCUTANEOUS, marketing status 'Prescription', reference drug Yes. There is no second sponsor, no generic, and no second brand. The full submission history in the record is: ORIG 1 approved 2020-11-25; SUPPL 1 (Efficacy) 2022-06-16; SUPPL 5 (Labeling) 2023-11-15; SUPPL 7 (Efficacy) 2024-12-20; SUPPL 8 (Labeling) 2025-08-21; SUPPL 9 (Efficacy) 2026-03-19. What each supplement CHANGED is not stated in this database and is not asserted here — the dates and classes are what the record carries. The acquired hypothalamic obesity indication is tied to the March 2026 supplement by the label's own Recent Major Changes stamp, not by this source alone.", "source": { "url": "https://api.fda.gov/drug/drugsfda.json?search=openfda.generic_name:\"setmelanotide\"&limit=5", "title": "Drugs@FDA — approved drug products database, queried for setmelanotide (openFDA)", "publisher": "FDA", "date": "2026-07-31" }, "verifiedAt": "2026-08-02" }, { "finding": "The FDA-approved labeling directs that a full body skin examination be performed prior to initiation and periodically during treatment with IMCIVREE, to monitor pre-existing and new pigmented skin lesions.", "note": "Recorded as a regulatory finding as well as a safety signal because of what it implies about supervision. FDA did not respond to the pigmentation effect with a warning to read; it responded with a scheduled clinical procedure, before initiation and repeatedly during treatment. That is a monitoring requirement that only exists inside a prescribing relationship. Note also that the label attributes the new and darkening nevi to the drug's 'pharmacologic effect' — this is the mechanism operating, not an idiosyncratic reaction, and it is on the label of the MC1-SELECTIVE compound in this class.", "source": { "url": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=70c3ccf7-4df0-4c75-ba07-fede9970c8d9", "title": "IMCIVREE (setmelanotide) injection, solution — Prescribing Information (current SPL)", "publisher": "DailyMed (U.S. National Library of Medicine)", "date": "2026-04-01", "quote": "Generalized or focal increases in skin pigmentation occurred in the majority of IMCIVREE-treated patients in clinical trials … IMCIVREE may also cause the development of new melanocytic nevi or darkening of pre-existing nevi due to its pharmacologic effect. Perform a full body skin examination prior to initiation and periodically during treatment with IMCIVREE to monitor pre-existing and new skin pigmented lesions." }, "verifiedAt": "2026-08-02" } ], "safetySignals": [ { "signal": "Warning — Disturbance in Sexual Arousal. Per the label, spontaneous penile erections and increased frequency of penile erections in males occurred in clinical trials with IMCIVREE, and sexual adverse reactions in females have occurred. The label instructs patients who have an erection lasting longer than 4 hours to seek emergency medical attention.", "note": "A melanocortin class effect appearing on the label of an agonist selected for MC4 activity. In the acquired hypothalamic obesity trial the label reports spontaneous or increased-frequency penile erections in 7% of IMCIVREE-treated patients versus 4% of placebo-treated patients, and in the trial of patients aged 2 to less than 6 years, spontaneous penile erections in 8% of IMCIVREE-treated patients. Recorded plainly because it is listed among the most common adverse reactions on a paediatric label, which is a different thing from a marketed benefit.", "source": { "url": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=70c3ccf7-4df0-4c75-ba07-fede9970c8d9", "title": "IMCIVREE (setmelanotide) injection, solution — Prescribing Information (current SPL)", "publisher": "DailyMed (U.S. National Library of Medicine)", "date": "2026-04-01", "quote": "Disturbance in Sexual Arousal: Spontaneous penile erections in males and sexual adverse reactions in females have occurred. Inform patients that these events may occur and instruct patients who have an erection lasting longer than 4 hours to seek emergency medical attention." }, "verifiedAt": "2026-08-02" }, { "signal": "Warning — Depression and Suicidal Ideation. Per the label, depression and suicidal ideation have occurred; the label directs monitoring for new onset or worsening depression or suicidal thoughts or behaviors, and states that discontinuing IMCIVREE should be considered if patients experience suicidal thoughts or behaviors or if clinically significant or persistent depression symptoms occur.", "note": "Depression appears in the label's list of most common adverse reactions at an incidence of 20% or greater in at least one indication. The label also reports depressed mood in 8% of IMCIVREE-treated patients in the trial of patients aged 2 to less than 6 years. This is a centrally acting drug and the label says so in the warning itself.", "source": { "url": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=70c3ccf7-4df0-4c75-ba07-fede9970c8d9", "title": "IMCIVREE (setmelanotide) injection, solution — Prescribing Information (current SPL)", "publisher": "DailyMed (U.S. National Library of Medicine)", "date": "2026-04-01", "quote": "Some drugs that target the central nervous system, such as IMCIVREE, may cause depression or suicidal ideation … Patients with a history of depression or suicidal ideation may be at increased risk for recurrent episodes while taking IMCIVREE." }, "verifiedAt": "2026-08-02" }, { "signal": "Warning and contraindication — serious hypersensitivity reactions, including anaphylaxis, have been reported with IMCIVREE, generally occurring within minutes to hours after injection. IMCIVREE is contraindicated in patients with a prior serious hypersensitivity reaction to setmelanotide or any of its excipients. Hypersensitivity including anaphylaxis also appears in the label's Postmarketing Experience section.", "note": "The only contraindication on this label, and it is a screening question that requires someone to ask it. Worth reading alongside the label's Description section, which lists the excipients — benzyl alcohol, carboxymethylcellulose sodium, edetate disodium dihydrate, a PEGylated phospholipid, mannitol and phenol among them. The contraindication reaches a prior serious reaction to the excipients, not only to setmelanotide itself.", "source": { "url": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=70c3ccf7-4df0-4c75-ba07-fede9970c8d9", "title": "IMCIVREE (setmelanotide) injection, solution — Prescribing Information (current SPL)", "publisher": "DailyMed (U.S. National Library of Medicine)", "date": "2026-04-01", "quote": "Serious hypersensitivity reactions, including anaphylaxis, have been reported with IMCIVREE. These reactions generally occurred within minutes to hours after injecting IMCIVREE … IMCIVREE is contraindicated in patients with a prior serious hypersensitivity reaction to setmelanotide or any of the excipients in IMCIVREE." }, "verifiedAt": "2026-08-02" }, { "signal": "Warning — Skin Hyperpigmentation, Darkening of Pre-Existing Nevi, and Development of New Melanocytic Nevi. Per the label, generalized or focal increases in skin pigmentation occurred in the majority of IMCIVREE-treated patients in clinical trials, an effect the label states is reversible on discontinuation, and IMCIVREE may also cause the development of new melanocytic nevi or darkening of pre-existing nevi.", "note": "The frequency is the part that gets lost: the majority of treated patients, not a minority. In the placebo-controlled period of the Bardet-Biedl syndrome trial the label reports hyperpigmentation disorders in 67% of IMCIVREE-treated patients versus 0% of placebo-treated patients. Skin hyperpigmentation heads the label's list of most common adverse reactions. Read this against the Mechanism of Action, which states setmelanotide has 20-fold LESS activity at MC1 than at MC4 — the selective compound still produced this in most patients, and FDA still required scheduled full body skin examinations.", "source": { "url": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=70c3ccf7-4df0-4c75-ba07-fede9970c8d9", "title": "IMCIVREE (setmelanotide) injection, solution — Prescribing Information (current SPL)", "publisher": "DailyMed (U.S. National Library of Medicine)", "date": "2026-04-01", "quote": "Generalized or focal increases in skin pigmentation occurred in the majority of IMCIVREE-treated patients in clinical trials … This effect is reversible upon discontinuation of the drug. IMCIVREE may also cause the development of new melanocytic nevi or darkening of pre-existing nevi due to its pharmacologic effect." }, "verifiedAt": "2026-08-02" }, { "signal": "Warning — Acute Adrenal Insufficiency in patients with acquired hypothalamic obesity. In a clinical trial of adults and pediatric patients aged 4 years and older with acquired HO and secondary adrenal insufficiency, the label reports that serious adverse reactions related to acute adrenal insufficiency were reported by 5% of IMCIVREE-treated patients and no placebo-treated patients.", "note": "New in March 2026 — this warning (section 5.5) and the sodium warning (5.6) are both stamped 03/2026 in the label's Recent Major Changes block, arriving with the acquired hypothalamic obesity indication. The expansion of an approval is not only an expansion of who may be treated; here it added two warnings that did not previously exist, both specific to the newly indicated population, both concerning serious endocrine events, and both separating from placebo in the trial that supported the expansion.", "source": { "url": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=70c3ccf7-4df0-4c75-ba07-fede9970c8d9", "title": "IMCIVREE (setmelanotide) injection, solution — Prescribing Information (current SPL)", "publisher": "DailyMed (U.S. National Library of Medicine)", "date": "2026-04-01", "quote": "In a clinical trial of adults and pediatric patients aged 4 years and older with acquired HO and secondary adrenal insufficiency, serious adverse reactions related to acute adrenal insufficiency were reported by 5% of IMCIVREE-treated patients and no placebo-treated patients. In patients with secondary adrenal insufficiency, monitor for clinical signs of acute adrenal insufficiency." }, "verifiedAt": "2026-08-02" }, { "signal": "Warning — Sodium Imbalance in patients with acquired hypothalamic obesity and central diabetes insipidus. In a clinical trial of adults and pediatric patients aged 4 years and older with acquired HO and concomitant central diabetes insipidus / arginine vasopressin deficiency, the label reports hyponatremia in 6% of IMCIVREE-treated patients versus 2% of placebo-treated patients, and hypernatremia in 5% of IMCIVREE-treated patients versus 4% of placebo-treated patients.", "note": "Read the two directions separately. Hyponatremia separated from placebo by a factor of three in the label's reported percentages; hypernatremia barely separated at all. Flattening both into 'sodium problems' loses the asymmetry. The label's response is serum sodium monitoring tied to changes in fluid intake and hydration status — again, laboratory monitoring inside a prescribing relationship rather than a caution to read.", "source": { "url": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=70c3ccf7-4df0-4c75-ba07-fede9970c8d9", "title": "IMCIVREE (setmelanotide) injection, solution — Prescribing Information (current SPL)", "publisher": "DailyMed (U.S. National Library of Medicine)", "date": "2026-04-01", "quote": "hyponatremia was reported in 6% of IMCIVREE-treated patients and 2% of placebo-treated patients, and hypernatremia was reported in 5% of IMCIVREE-treated patients and 4% of placebo-treated patients. In patients with acquired HO and concomitant DI/AVP deficiency, monitor serum sodium levels with changes in fluid intake and hydration status." }, "verifiedAt": "2026-08-02" }, { "signal": "Per the label, the most common adverse reactions at an incidence of 20% or greater in at least one indication were skin hyperpigmentation, injection site reactions, nausea, headache, diarrhea, abdominal pain, vomiting, depression, and spontaneous penile erection.", "note": "Reproduced in full because two entries on this list — depression and spontaneous penile erection — are the kind of adverse reaction that gets marketed as a feature elsewhere in the melanocortin market, and they are here at an incidence of 20% or greater in at least one indication, on a label that also covers children. The 20% threshold is FDA's, not ours, and the label does not break the figure out by reaction in this summary.", "source": { "url": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=70c3ccf7-4df0-4c75-ba07-fede9970c8d9", "title": "IMCIVREE (setmelanotide) injection, solution — Prescribing Information (current SPL)", "publisher": "DailyMed (U.S. National Library of Medicine)", "date": "2026-04-01", "quote": "Most common adverse reactions (incidence ≥20% in at least 1 indication) included skin hyperpigmentation, injection site reactions, nausea, headache, diarrhea, abdominal pain, vomiting, depression, and spontaneous penile erection." }, "verifiedAt": "2026-08-02" } ], "faqs": [ { "question": "Is setmelanotide FDA-approved?", "answer": "Yes. Setmelanotide is the active ingredient of IMCIVREE, approved by FDA under NDA 213793 with sponsor Rhythm and marketing status 'Prescription' in the Drugs@FDA database. The original application was approved on 25 November 2020 under priority review as a Type 1 New Molecular Entity carrying an orphan submission property, and six supplements follow it in the record, the most recent efficacy supplement approved on 19 March 2026. Drugs@FDA lists exactly one application and one product containing setmelanotide: setmelanotide acetate as a solution for subcutaneous use. Approval is specific to that product and to the indications in its labeling — it is not a general endorsement of the molecule, and there is no approved generic or second brand.", "source": { "url": "https://api.fda.gov/drug/drugsfda.json?search=openfda.generic_name:\"setmelanotide\"&limit=5", "title": "Drugs@FDA — approved drug products database, queried for setmelanotide (openFDA)", "publisher": "FDA", "date": "2026-07-31" }, "verifiedAt": "2026-08-02" }, { "question": "Is Imcivree approved for general weight loss or ordinary obesity?", "answer": "No. The FDA-approved labeling for IMCIVREE excludes it in its Limitations of Use: IMCIVREE 'is not indicated for the treatment of patients with the following conditions as IMCIVREE would not be expected to be effective: … Other types of obesity not related to acquired HO, BBS, or POMC, PCSK1, or LEPR deficiency, including obesity associated with other genetic syndromes and general (polygenic) obesity.' Read the standard the label sets — not that the effect is unproven in these patients, but that it 'would not be expected to be effective', which follows from the mechanism the label describes: setmelanotide is an MC4 receptor agonist and the label frames its effect around obesity 'associated with insufficient activation of the MC4 receptor'. The label also excludes patients whose POMC, PCSK1 or LEPR variants are classified as benign or likely benign, so a genetic test result alone does not establish eligibility.", "source": { "url": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=70c3ccf7-4df0-4c75-ba07-fede9970c8d9", "title": "IMCIVREE (setmelanotide) injection, solution — Prescribing Information (current SPL)", "publisher": "DailyMed (U.S. National Library of Medicine)", "date": "2026-04-01", "quote": "Limitations of Use: IMCIVREE is not indicated for the treatment of patients with the following conditions as IMCIVREE would not be expected to be effective: • Obesity due to suspected POMC, PCSK1, or LEPR deficiency with POMC, PCSK1, or LEPR variants classified as benign or likely benign. • Other types of obesity not related to acquired HO, BBS, or POMC, PCSK1, or LEPR deficiency, including obesity associated with other genetic syndromes and general (polygenic) obesity." }, "verifiedAt": "2026-08-02" }, { "question": "Does setmelanotide cause skin darkening?", "answer": "Yes, and the FDA label treats it as an expected pharmacologic effect rather than a rare reaction. The labeling states that 'Generalized or focal increases in skin pigmentation occurred in the majority of IMCIVREE-treated patients in clinical trials', that the effect 'is reversible upon discontinuation of the drug', and that IMCIVREE 'may also cause the development of new melanocytic nevi or darkening of pre-existing nevi due to its pharmacologic effect'. Because of that, the label directs prescribers to 'Perform a full body skin examination prior to initiation and periodically during treatment with IMCIVREE to monitor pre-existing and new skin pigmented lesions.' Skin hyperpigmentation heads the label's list of most common adverse reactions, and in the placebo-controlled period of the Bardet-Biedl syndrome trial the label reports hyperpigmentation disorders in 67% of IMCIVREE-treated patients versus 0% of placebo-treated patients. Note that the label describes setmelanotide as having 20-fold less activity at the melanocortin 1 (MC1) receptor — the pigmentation receptor — than at MC4.", "source": { "url": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=70c3ccf7-4df0-4c75-ba07-fede9970c8d9", "title": "IMCIVREE (setmelanotide) injection, solution — Prescribing Information (current SPL)", "publisher": "DailyMed (U.S. National Library of Medicine)", "date": "2026-04-01", "quote": "Generalized or focal increases in skin pigmentation occurred in the majority of IMCIVREE-treated patients in clinical trials … Perform a full body skin examination prior to initiation and periodically during treatment with IMCIVREE to monitor pre-existing and new skin pigmented lesions." }, "verifiedAt": "2026-08-02" }, { "question": "What human evidence supports setmelanotide?", "answer": "Four Phase 3 registrations, all sponsored by Rhythm Pharmaceuticals, all with results posted, and all of which administered setmelanotide to human participants against a placebo arm. The largest is NCT05774756, a randomized, double-blinded, placebo-controlled trial in acquired hypothalamic obesity with an actual enrolment of 143 and a primary completion date of 18 March 2025; the FDA label reports that after 52 weeks the mean percent change in BMI compared to placebo was -18.40%. The others are NCT03746522 in Bardet-Biedl syndrome (52 enrolled, completed 2021), and NCT02896192 and NCT03287960 in POMC/PCSK1 and LEPR deficiency respectively (15 enrolled each, both completed 2020), which were open-label trials with a double-blind withdrawal period. Two limits are worth stating plainly: the POMC/PCSK1 and LEPR efficacy analyses covered 21 patients between them, and none of these trials studied general obesity — the label states that safety and effectiveness have not been established in otherwise healthy patients with obesity.", "source": { "url": "https://clinicaltrials.gov/study/NCT05774756", "title": "A Trial of Setmelanotide in Acquired Hypothalamic Obesity", "publisher": "ClinicalTrials.gov", "date": "2025-03-18", "quote": "A Trial of Setmelanotide in Acquired Hypothalamic Obesity" }, "verifiedAt": "2026-08-02" }, { "question": "Was Imcivree's approval expanded in 2026?", "answer": "Yes. Drugs@FDA records an efficacy supplement to NDA 213793 (SUPPL 9) approved on 19 March 2026 under priority review with an orphan submission property, and the current Structured Product Label's Recent Major Changes block stamps Indications and Usage 03/2026 together with two new Warnings and Precautions subsections, 5.5 and 5.6. The current label indicates IMCIVREE for adults and pediatric patients aged 4 years and older with acquired hypothalamic obesity — obesity following injury to or dysfunction of the hypothalamus — alongside the pre-existing syndromic and monogenic indications. This matters for how the drug is described: acquired hypothalamic obesity is not a genetic condition, so summaries calling IMCIVREE a genetic-obesity-only therapy are now out of date. The two new warnings arrived with it and are specific to that population: acute adrenal insufficiency, and sodium imbalance in patients with concomitant central diabetes insipidus.", "source": { "url": "https://api.fda.gov/drug/drugsfda.json?search=openfda.generic_name:\"setmelanotide\"&limit=5", "title": "Drugs@FDA — approved drug products database, queried for setmelanotide (openFDA)", "publisher": "FDA", "date": "2026-07-31" }, "verifiedAt": "2026-08-02" }, { "question": "What are the risks of setmelanotide?", "answer": "The FDA label for IMCIVREE carries six Warnings and Precautions and one contraindication. The warnings are: disturbance in sexual arousal, with spontaneous penile erections in males and sexual adverse reactions in females, and an instruction that an erection lasting longer than 4 hours requires emergency medical attention; depression and suicidal ideation, with monitoring directed and discontinuation to be considered; serious hypersensitivity reactions including anaphylaxis, generally occurring within minutes to hours after injection; skin hyperpigmentation, darkening of pre-existing nevi and development of new melanocytic nevi, requiring scheduled full body skin examinations; acute adrenal insufficiency in patients with acquired hypothalamic obesity, reported as a serious adverse reaction in 5% of IMCIVREE-treated patients and no placebo-treated patients in one trial; and sodium imbalance in patients with acquired hypothalamic obesity and central diabetes insipidus. The single contraindication is a prior serious hypersensitivity reaction to setmelanotide or any of the excipients. The label lists the most common adverse reactions, at an incidence of 20% or greater in at least one indication, as skin hyperpigmentation, injection site reactions, nausea, headache, diarrhea, abdominal pain, vomiting, depression, and spontaneous penile erection.", "source": { "url": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=70c3ccf7-4df0-4c75-ba07-fede9970c8d9", "title": "IMCIVREE (setmelanotide) injection, solution — Prescribing Information (current SPL)", "publisher": "DailyMed (U.S. National Library of Medicine)", "date": "2026-04-01", "quote": "Most common adverse reactions (incidence ≥20% in at least 1 indication) included skin hyperpigmentation, injection site reactions, nausea, headache, diarrhea, abdominal pain, vomiting, depression, and spontaneous penile erection." }, "verifiedAt": "2026-08-02" }, { "question": "Who is eligible to be prescribed Imcivree?", "answer": "Per the FDA-approved labeling, IMCIVREE is indicated to reduce excess body weight and maintain weight reduction long term in adults and pediatric patients aged 4 years and older with acquired hypothalamic obesity, and in adults and pediatric patients aged 2 years and older with syndromic or monogenic obesity due to Bardet-Biedl syndrome, or due to pro-opiomelanocortin (POMC), proprotein convertase subtilisin/kexin type 1 (PCSK1) or leptin receptor (LEPR) deficiency 'confirmed by genetic testing demonstrating variants in POMC, PCSK1, or LEPR genes that are interpreted as pathogenic, likely pathogenic, or of uncertain significance (VUS)'. Three details are routinely dropped in summaries: the age floor differs by condition, the monogenic indications require a confirmatory genetic test rather than a clinical impression, and variants classified as benign or likely benign are expressly excluded by the label's Limitations of Use. Whether an individual patient meets these criteria is a determination for a licensed prescriber.", "source": { "url": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=70c3ccf7-4df0-4c75-ba07-fede9970c8d9", "title": "IMCIVREE (setmelanotide) injection, solution — Prescribing Information (current SPL)", "publisher": "DailyMed (U.S. National Library of Medicine)", "date": "2026-04-01", "quote": "IMCIVREE is indicated to reduce excess body weight and maintain weight reduction long term in adults and pediatric patients aged … : 4 years and older with acquired hypothalamic obesity (HO) … 2 years and older with syndromic or monogenic obesity due to: o Bardet-Biedl syndrome (BBS) o Pro-opiomelanocortin (POMC), proprotein convertase subtilisin/kexin type 1 (PCSK1), or leptin receptor (LEPR) deficiency confirmed by genetic testing …" }, "verifiedAt": "2026-08-02" } ] }, { "slug": "survodutide", "name": "Survodutide", "aliases": [ "BI 456906", "BI456906" ], "url": "https://peptides101.com/compounds/survodutide", "moleculeNote": "A single investigational peptide that agonises two receptors — the glucagon receptor (GCGR) and the glucagon-like peptide-1 receptor (GLP-1R) — described as a 'glucagon receptor/glucagon-like peptide-1 receptor dual agonist' in the Nature Medicine Phase 3 report and as 'an investigational glucagon receptor-GLP-1 receptor dual agonist' in the NEJM Phase 3 report. 'Survodutide' and 'BI 456906' denote one molecule; the trial registrations use both names interchangeably, and there is no fragment-versus-full-length ambiguity of the kind that makes TB-500 records unreadable. The ambiguity is somewhere else entirely: nothing verifies that a vial sold as 'survodutide' by a research-chemical vendor contains that molecule, at that purity, at any stated content. Survodutide is not an ingredient in any FDA-approved drug product (recorded, sourced, under FDA findings), so no vial of it originates from an approved supply.", "quickAnswer": "Survodutide (BI 456906) is not approved by FDA for any indication — it returns no match in Drugs@FDA on any query field, and in a December 2024 warning letter FDA stated that 'No FDA-approved applications pursuant to section 505 of the FD&C Act … are in effect for these products' after finding a seller offering 'SURVODUTIDE' among products it called unapproved new drugs, holding that 'FOR RESEARCH USE ONLY' labeling did not defeat evidence of intended human use. It is in active clinical development by Boehringer Ingelheim, with Phase 3 trials still recruiting. Its human evidence is nonetheless real: two Phase 3 randomised, double-blind, placebo-controlled trials of once-weekly subcutaneous survodutide were published on 7 June 2026 — SYNCHRONIZE-1 in the New England Journal of Medicine (725 adults with obesity, 76 weeks) and SYNCHRONIZE-MASLD in Nature Medicine (216 adults, 48 weeks) — and both met their primary endpoints. Those trials used the sponsor's investigational material, gastrointestinal adverse events were the most common in both, and the largest survodutide trial conducted, a cardiovascular safety study of 5,531 participants, completed on 30 June 2026 with no results posted as of 2 August 2026.", "fdaStatus": { "value": "investigational", "note": "In active clinical development with an identifiable sponsor and registered trials. Not approved. Being in trials is not evidence that it works. THE ACTIVE-DEVELOPMENT TEST WAS RUN, NOT ASSUMED, because a terminated programme is not investigational — it is a programme that failed, and this vertical routinely sells 'in clinical trials' on the strength of a trial that stopped years ago. Queried against the ClinicalTrials.gov API on 2026-08-02: totalCount 24 survodutide registrations, of which 23 name Boehringer Ingelheim as lead sponsor and one is an investigator-initiated Phase 2 study at University Medical Center Groningen (NCT07206290, not yet recruiting). None of the 24 is terminated, withdrawn or suspended. Two Phase 3 trials are RECRUITING right now — LIVERAGE (NCT06632444, estimated 1,800 participants, estimated primary completion 2031-12-27) and LIVERAGE-Cirrhosis (NCT06632457, estimated 1,590) — and a Phase 1 study (NCT07407348) began recruiting 2026-03-11. Nothing in the programme reads as terminated or withdrawn. THE NOT-APPROVED HALF is carried separately and sourced separately: Drugs@FDA returns no match for survodutide on any of four query fields (see FDA findings). SCOPE LIMIT, stated because the alternative is to imply knowledge this record does not have: 'investigational' describes the development programme, not any marketing application. This record makes no claim about whether a new drug application for survodutide has been submitted, accepted or is pending. FDA does not publish that, and no primary document establishing it was located on 2026-08-02.", "source": { "url": "https://clinicaltrials.gov/study/NCT06632444", "title": "LIVERAGE — A Randomised, Double-blind, Placebo-controlled, Multicentre, Phase III Trial Evaluating Long-term Efficacy and Safety of Survodutide Weekly Injections in Adult Participants With Noncirrhotic Non-alcoholic Steatohepatitis (NASH/MASH) and Fibrosis", "publisher": "ClinicalTrials.gov", "date": "2026-07-09" }, "verifiedAt": "2026-08-02" }, "compoundingStatus": null, "evidence": { "tier": "proven-in-humans", "humanAdministrationChecked": true, "note": "ADMINISTRATION CHECK PASSED, EXPLICITLY AND PER-STUDY. Survodutide is a synthetic investigational drug, not an endogenous peptide, so the biomarker trap that empties MOTS-c's and TB-500's apparent trial counts cannot apply — but the check was run anyway rather than assumed, because assuming it is the failure this schema exists to catch. TRIAL 1 — SYNCHRONIZE-1 (NCT06066515), Phase 3, randomised, quadruple-masked, placebo-controlled, 76 weeks, enrolment 726 ACTUAL, lead sponsor Boehringer Ingelheim, status COMPLETED (primary completion 2025-12-02 ACTUAL, completion 2026-02-20 ACTUAL). The ClinicalTrials.gov intervention records read 'once weekly subcutaneous injection' for both survodutide and placebo. In the NEJM report, investigators randomised 725 adults with obesity, or with overweight and at least one obesity-related complication and without diabetes, 1:1:1 to subcutaneous survodutide or placebo, and reported that at week 76 the mean change in body weight by the treatment-regimen estimand was substantially greater in both survodutide groups than in the placebo group, with both primary end points met (P<0.001 for all comparisons with placebo). TRIAL 2 — SYNCHRONIZE-MASLD, Phase 3, randomised 2:1, double-blind, placebo-controlled, 48 weeks, 216 adults, reported in Nature Medicine the same day. Participants were 'treated with once-weekly subcutaneous injections of survodutide … or placebo'; both co-primary endpoints — reduction in MRI-PDFF-assessed liver fat content and percentage change in body weight — were met. The drug was ADMINISTERED in both. Neither measures an endogenous peptide. WHAT THE TIER MEANS AND DOES NOT MEAN. It means efficacy on the endpoints those two trials measured — body weight, and MRI-assessed liver fat content — is established by adequate, well-controlled human trials. It does NOT mean approved: survodutide is approved by FDA for nothing, and FDA has stated in a warning letter that products sold under this name 'are not generally recognized as safe and effective'. It does not mean the outcomes that matter longest are known — the cardiovascular safety trial (NCT06077864, n=5,531 ACTUAL, Boehringer Ingelheim, Phase 3) completed 2026-06-30 and had posted no results on 2026-08-02, and the two Phase 3 MASH trials do not estimate primary completion until 2031. And it does not transfer to grey-market product: both published trials used the sponsor's investigational material under trial conditions. PER-ARM FIGURES ARE LEFT TO THE CITED PAPERS. An amount beside a frequency reconstructs a regimen, and this record does not publish one in any field.", "source": { "url": "https://pubmed.ncbi.nlm.nih.gov/42253238/", "title": "Survodutide Once Weekly for the Treatment of Adults with Obesity", "publisher": "The New England Journal of Medicine", "date": "2026-06-07", "quote": "In this phase 3, double-blind trial, we randomly assigned adults with a body-mass index (BMI; the weight in kilograms divided by the square of the height in meters) of 30 or higher, or 27 or higher with at least one obesity-related complication (excluding diabetes), in a 1:1:1 ratio to receive once-weekly survodutide administered subcutaneously […] or placebo, in addition to counseling for lifestyle modification." }, "verifiedAt": "2026-08-02" }, "fdaApproval": null, "fdaFindings": [ { "finding": "In a warning letter of 10 December 2024 to Xcel Research LLC, FDA found that products the firm offered for sale under the name 'SURVODUTIDE', among others, are unapproved new drugs introduced or delivered for introduction into interstate commerce in violation of sections 505(a) and 301(d) of the Federal Food, Drug, and Cosmetic Act.", "note": "This is the document that makes survodutide unusual on this site: FDA has named it, in capitals, in an enforcement letter, alongside retatrutide and semaglutide. Read the scope precisely and in both directions. It is a finding about ONE FIRM'S PRODUCTS — Xcel Research LLC, at xcelpeptides.com, reviewed by FDA in October 2024. It is not a finding about survodutide's pharmacology, it is not a finding that the Boehringer Ingelheim trials are wrong, and it is not a statement about any other vendor. What it does establish, and what the market reading of 'it's just a research peptide' does not survive, is FDA's legal characterisation of survodutide sold this way.", "source": { "url": "https://www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/warning-letters/xcel-research-llc-694608-12102024", "title": "Warning Letter — Xcel Research LLC (MARCS-CMS 694608)", "publisher": "FDA", "date": "2024-12-10", "quote": "As described below, your “RETA” (Retatrutide), “CagriLean” (Cagrilintide and Semaglutide), “CAGRILINTIDE,” “MAZDUTIDE,” “SEMA” (Semaglutide), “SURVODUTIDE,” and “SERMORELIN,” products are unapproved new drugs introduced or delivered for introduction into interstate commerce in violation of sections 505(a) and 301(d) of the Federal Food, Drug, and Cosmetic Act (FD&C Act), 21 U.S.C. 355(a) and 331(d)." }, "verifiedAt": "2026-08-02" }, { "finding": "In the same letter, FDA held that labeling survodutide and the other products 'FOR RESEARCH USE ONLY' and 'NOT INTENDED FOR HUMAN USE' did not prevent them from being drugs, because evidence obtained from the firm's website established that the products were intended to be drugs for human use.", "note": "The research-use-only theory, tested against survodutide specifically rather than borrowed from another compound's record. FDA's method is worth reading because it is evidentiary rather than rhetorical: intended use is established from the seller's own marketing copy, and a disclaimer contradicted by that copy is not a defence. The survodutide claims FDA quoted back at this firm are structure/function and disease claims dressed in research language — that the substance 'can help regulate blood glucose levels more effectively than targeting either receptor alone' and 'has shown promise in stabilizing blood sugar levels, which is crucial for managing conditions like diabetes'. That construction — a benefit asserted of the compound, hedged with 'in research subjects' — is the exhibit, not the shield. It is also precisely the construction this site's editorial policy refuses.", "source": { "url": "https://www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/warning-letters/xcel-research-llc-694608-12102024", "title": "Warning Letter — Xcel Research LLC (MARCS-CMS 694608)", "publisher": "FDA", "date": "2024-12-10", "quote": "Despite statements on your product labeling marketing your products, “FOR RESEARCH USE ONLY” and “NOT INTENDED FOR HUMAN USE,” evidence obtained from your website establishes that your products are intended to be drugs for human use." }, "verifiedAt": "2026-08-02" }, { "finding": "FDA stated in the same letter that the products, including 'SURVODUTIDE', are not generally recognized as safe and effective for the referenced uses and are therefore new drugs, and that no FDA-approved applications under section 505 of the FD&C Act are in effect for these products.", "note": "Recorded separately from the violation finding above because it answers a different question — 'has FDA approved anything containing survodutide?' — and because the two get merged everywhere else. Note the sentence is scoped to 'these products', i.e. the firm's, which is why the general not-approved claim on this record rests on Drugs@FDA below rather than on this sentence alone. Two independent documents, one conclusion.", "source": { "url": "https://www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/warning-letters/xcel-research-llc-694608-12102024", "title": "Warning Letter — Xcel Research LLC (MARCS-CMS 694608)", "publisher": "FDA", "date": "2024-12-10", "quote": "No FDA-approved applications pursuant to section 505 of the FD&C Act, 21 U.S.C. 355, are in effect for these products." }, "verifiedAt": "2026-08-02" }, { "finding": "Survodutide does not appear in Drugs@FDA. Queried through the openFDA drug/drugsfda endpoint on 2026-08-02 across four fields — generic name, brand name, active-ingredient name and unfielded full text — every query returned NOT_FOUND, as did the drug/label endpoint.", "note": "A NOT_FOUND is only as good as the query that produced it, so the query was controlled. In the same session, on the same endpoint, `products.active_ingredients.name:\"TIRZEPATIDE\"` returned 2 results — the field name and syntax are correct, and the absence is about survodutide, not about the request. This is the correction of a real failure mode in this library: a false 'sermorelin is not in Drugs@FDA' claim was produced by querying a field whose openFDA block was empty. WHAT THIS ABSENCE MEANS. Drugs@FDA lists approved applications. Survodutide is in neither an approved application nor, therefore, an approved product, which is the not-approved half of its status. WHAT IT DOES NOT MEAN: Drugs@FDA does not list investigational drugs at all, so absence from it is not evidence about the development programme in either direction. The development programme is sourced separately, to the trial registrations.", "source": { "url": "https://api.fda.gov/drug/drugsfda.json?search=products.active_ingredients.name:%22SURVODUTIDE%22&limit=5", "title": "Drugs@FDA (openFDA drug/drugsfda) — query for active ingredient SURVODUTIDE", "publisher": "FDA", "date": "2026-07-31" }, "verifiedAt": "2026-08-02" }, { "finding": "Survodutide appears in none of Categories 1, 2 or 3 of FDA's list of bulk drug substances nominated for use in compounding under section 503A, updated 2026-05-14.", "note": "Recorded to close a misreading, not to assert a status — which is why this record carries no compoundingStatus field at all. Verified first-hand on 2026-08-02 by fetching the PDF with a browser user-agent and extracting its text locally: zero hits for 'survodutide' across all seven pages. Absence from this list cannot by itself distinguish 'nominated then withdrawn' from 'never nominated' from 'never on the nomination track at all', and no document was located that resolves which of those applies to survodutide. So the absence is recorded and the status is left blank. Two of the three statutory 503A conditions for a bulk drug substance are verifiable from this record's own sources and both fail: survodutide does not appear on the 503A bulks list (this finding), and it is not a component of an FDA-approved drug product (the Drugs@FDA finding above). The third condition — whether an applicable USP or NF monograph exists — was NOT verified against a primary document and is therefore not asserted here in either direction. Unlike retatrutide, survodutide has no FDA letter walking through all three prongs, and this record does not manufacture one by analogy.", "source": { "url": "https://www.fda.gov/media/94155/download", "title": "Bulk Drug Substances Nominated for Use in Compounding Under Section 503A of the Federal Food, Drug, and Cosmetic Act", "publisher": "FDA", "date": "2026-05-14" }, "verifiedAt": "2026-08-02" } ], "safetySignals": [ { "signal": "In the Phase 3 SYNCHRONIZE-1 trial (n=725), investigators reported that the most common adverse events were gastrointestinal symptoms, typically mild to moderate, occurring in 80.9% of participants in the lower-dose survodutide group and 89.7% in the higher-dose survodutide group, versus 47.9% in the placebo group. No deaths were reported.", "note": "Attributed to the trial, and scoped to it. Read the placebo column before reading the survodutide columns: 47.9% of participants on placebo also reported gastrointestinal adverse events, so the arithmetic difference is the signal, not the raw incidence. Read the gradient too — the higher-dose arm reported a higher incidence than the lower-dose arm, which is the pattern that matters most for anyone self-administering an unapproved vial with no titration schedule and no prescriber. Bounds: 725 participants over 76 weeks cannot characterise uncommon or long-latency harms, and 'no deaths were reported' is a statement about this trial, not about the molecule.", "source": { "url": "https://pubmed.ncbi.nlm.nih.gov/42253238/", "title": "Survodutide Once Weekly for the Treatment of Adults with Obesity", "publisher": "The New England Journal of Medicine", "date": "2026-06-07", "quote": "The most common adverse events were gastrointestinal symptoms (typically mild to moderate), which occurred in 80.9% of the participants in the [lower-dose] group, in 89.7% of those in the [higher-dose] group, and in 47.9% of those in the placebo group. No deaths were reported." }, "verifiedAt": "2026-08-02" }, { "signal": "In the Phase 3 SYNCHRONIZE-MASLD trial (n=216), investigators reported that the most frequently reported adverse events with survodutide were gastrointestinal, commonly occurring during dose escalation, and generally of mild-to-moderate severity.", "note": "Recorded as its own entry rather than folded into the SYNCHRONIZE-1 note, because it is a second trial, a different population and a different journal reaching the same characterisation — which is worth more than one trial saying it twice. The clause 'commonly occurring during dose escalation' is the load-bearing one and it describes a condition that only exists inside a trial: escalation there is protocol-defined, monitored, and reversible by an investigator. The authors also state the trial's own limitations verbatim — 'short trial duration (48 weeks) and limited global reach (participants recruited in the United States and Spain)'.", "source": { "url": "https://pubmed.ncbi.nlm.nih.gov/42252333/", "title": "Survodutide in adults with obesity and metabolic dysfunction-associated steatotic liver disease: SYNCHRONIZE-MASLD, a randomized, double-blind, placebo-controlled phase 3 trial", "publisher": "Nature Medicine", "date": "2026-06-07", "quote": "The most frequently reported adverse events with survodutide were gastrointestinal, commonly occurring during dose escalation, and were generally of mild-to-moderate severity." }, "verifiedAt": "2026-08-02" }, { "signal": "The largest survodutide trial conducted — a Phase 3, randomised, double-blind, event-driven cardiovascular safety study in participants with overweight or obesity, enrolment 5,531 ACTUAL, lead sponsor Boehringer Ingelheim — completed on 2026-06-30 and had no results posted on ClinicalTrials.gov as of 2026-08-02.", "note": "Recorded as a safety signal because an unreported cardiovascular safety trial IS the safety position, and the alternative — saying nothing — reads as though the question were settled. Verified against the ClinicalTrials.gov API on 2026-08-02: overall status COMPLETED, primary completion 2026-06-01 ACTUAL, completion 2026-06-30 ACTUAL, hasResults false, no results-first-submitted date. State only what the registry states. This is NOT a claim that the trial found a problem, and it is NOT a claim that it found none. It is a claim that the largest body of cardiovascular safety data on this molecule is not yet public, one month after the trial closed. Any source telling you survodutide's cardiovascular safety is established is not reading this registration.", "source": { "url": "https://clinicaltrials.gov/study/NCT06077864", "title": "A Phase 3, Randomised, Double-blind, Parallel-group, Event-driven, Cardiovascular Safety Study With BI 456906 Administered Subcutaneously Compared With Placebo in Participants With Overweight or Obesity", "publisher": "ClinicalTrials.gov", "date": "2026-07-23" }, "verifiedAt": "2026-08-02" }, { "signal": "FDA stated that products sold under the name 'SURVODUTIDE', among others, are not generally recognized as safe and effective for the uses claimed on the seller's website.", "note": "Placed under safety signals as well as FDA findings because of how it is misread. 'Not generally recognized as safe and effective' is a term of art describing the ABSENCE of an approval finding — it is the statutory test that makes something a 'new drug' requiring an approved application. It is not a finding that the Phase 3 trials failed; they did not. Both readings are live in this vertical and both are wrong: sellers cite the trials as though they were an approval, and critics cite this sentence as though it were a negative efficacy finding. The honest position is that no FDA safety and effectiveness determination for survodutide exists, and an unapproved vial has had no FDA review of its identity, purity or content at all.", "source": { "url": "https://www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/warning-letters/xcel-research-llc-694608-12102024", "title": "Warning Letter — Xcel Research LLC (MARCS-CMS 694608)", "publisher": "FDA", "date": "2024-12-10", "quote": "Your “RETA” (Retatrutide), “CagriLean” (Cagrilintide and Semaglutide), “CAGRILINTIDE,” “MAZDUTIDE,” “SEMA” (Semaglutide), “SURVODUTIDE,” and “SERMORELIN” products are not generally recognized as safe and effective for the above referenced uses and, therefore, are “new drugs” under section 201(p) of the FD&C Act, 21 U.S.C. 321(p)." }, "verifiedAt": "2026-08-02" } ], "faqs": [ { "question": "Is survodutide FDA-approved in 2026?", "answer": "No. Survodutide is not approved by FDA for any indication, in any population, by any route. Drugs@FDA, queried through the openFDA drug/drugsfda endpoint on 2 August 2026, returns no match for survodutide on generic name, brand name, active-ingredient name or unfielded full text, and the drug/label endpoint returns no match either — while the same endpoint returns results for tirzepatide on the same field in the same session, so the absence is about survodutide and not about the query. FDA said the same thing in different words in a warning letter of 10 December 2024, writing of a seller's survodutide and other products that 'No FDA-approved applications pursuant to section 505 of the FD&C Act, 21 U.S.C. 355, are in effect for these products.' Survodutide is an investigational Boehringer Ingelheim molecule still in Phase 3 development; this record makes no claim about whether a marketing application has been submitted, because FDA does not publish that and no primary document establishing it was located.", "source": { "url": "https://api.fda.gov/drug/drugsfda.json?search=products.active_ingredients.name:%22SURVODUTIDE%22&limit=5", "title": "Drugs@FDA (openFDA drug/drugsfda) — query for active ingredient SURVODUTIDE", "publisher": "FDA", "date": "2026-07-31" }, "verifiedAt": "2026-08-02" }, { "question": "Is it legal to buy survodutide sold 'for research use only'?", "answer": "No — FDA has addressed that exact labeling, on survodutide by name. In a warning letter of 10 December 2024 to Xcel Research LLC, FDA wrote that 'Despite statements on your product labeling marketing your products, \"FOR RESEARCH USE ONLY\" and \"NOT INTENDED FOR HUMAN USE,\" evidence obtained from your website establishes that your products are intended to be drugs for human use.' FDA found the firm's 'SURVODUTIDE' product, among others, to be an unapproved new drug whose introduction or delivery for introduction into interstate commerce violates sections 301(d) and 505(a) of the Federal Food, Drug, and Cosmetic Act. The mechanism is what matters: intended use is established from the seller's own marketing copy, so a disclaimer contradicted by that copy is not a defence. Scope, stated honestly — this letter concerns one firm's products, reviewed by FDA in October 2024. It is cited as evidence of FDA's legal position on survodutide sold this way, not as a finding about any other vendor.", "source": { "url": "https://www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/warning-letters/xcel-research-llc-694608-12102024", "title": "Warning Letter — Xcel Research LLC (MARCS-CMS 694608)", "publisher": "FDA", "date": "2024-12-10", "quote": "Despite statements on your product labeling marketing your products, “FOR RESEARCH USE ONLY” and “NOT INTENDED FOR HUMAN USE,” evidence obtained from your website establishes that your products are intended to be drugs for human use." }, "verifiedAt": "2026-08-02" }, { "question": "Is there human evidence that survodutide works?", "answer": "Yes — survodutide is one of the few compounds sold on the peptide market with published, peer-reviewed Phase 3 randomised trials. In SYNCHRONIZE-1 (NCT06066515), a 76-week phase 3 double-blind trial reported in the New England Journal of Medicine on 7 June 2026, investigators randomised 725 adults with obesity — or with overweight and at least one obesity-related complication, excluding diabetes — in a 1:1:1 ratio to once-weekly subcutaneous survodutide or placebo, and reported that both primary end points were met, with substantially greater reduction in body weight at week 76 in both survodutide groups than with placebo (P<0.001 for all comparisons with placebo). A second phase 3 trial, SYNCHRONIZE-MASLD, published in Nature Medicine the same day, randomised 216 adults with obesity and at-risk metabolic dysfunction-associated steatotic liver disease 2:1 to once-weekly subcutaneous survodutide or placebo and met both co-primary endpoints — liver fat content by MRI-PDFF and percentage change in body weight. Both trials were funded by Boehringer Ingelheim and used the sponsor's investigational material. That evidence describes the molecule under trial conditions. It says nothing about the contents, purity or identity of a vial sold as 'survodutide' by a research-chemical vendor, and survodutide is not an ingredient in any FDA-approved drug product, so no such vial comes from an approved supply.", "source": { "url": "https://pubmed.ncbi.nlm.nih.gov/42253238/", "title": "Survodutide Once Weekly for the Treatment of Adults with Obesity", "publisher": "The New England Journal of Medicine", "date": "2026-06-07", "quote": "In this phase 3, double-blind trial, we randomly assigned adults with a body-mass index (BMI; the weight in kilograms divided by the square of the height in meters) of 30 or higher, or 27 or higher with at least one obesity-related complication (excluding diabetes), in a 1:1:1 ratio to receive once-weekly survodutide administered subcutaneously […] or placebo, in addition to counseling for lifestyle modification." }, "verifiedAt": "2026-08-02" }, { "question": "Why do different sources report different weight-loss numbers for survodutide?", "answer": "Because the same trial can be analysed under more than one estimand, and the two answer different questions. The Nature Medicine report of SYNCHRONIZE-MASLD publishes both in the same abstract, which makes the gap checkable rather than arguable: 84.2% of survodutide-treated patients versus 24.3% on placebo had at least a 30% reduction in liver fat content 'using the efficacy estimand', while the treatment regimen estimand for the same endpoint was 68.5% versus 28.6%; mean percentage change in body weight was -12.2% with survodutide and -1.0% with placebo using the efficacy estimand, and -8.7% versus -1.4% using the treatment regimen estimand. An efficacy estimand describes what happened in participants who stayed on treatment as intended; a treatment-regimen estimand incorporates early discontinuation and protocol deviations, so it is closer to what happens in practice and it is consistently the smaller number. In SYNCHRONIZE-1, the New England Journal of Medicine reports that 'The primary efficacy analysis was conducted according to the treatment-regimen estimand'. Neither figure is wrong; a figure quoted without saying which estimand produced it is unusable. Check which one any number you are given comes from.", "source": { "url": "https://pubmed.ncbi.nlm.nih.gov/42252333/", "title": "Survodutide in adults with obesity and metabolic dysfunction-associated steatotic liver disease: SYNCHRONIZE-MASLD, a randomized, double-blind, placebo-controlled phase 3 trial", "publisher": "Nature Medicine", "date": "2026-06-07", "quote": "In total, 84.2% of survodutide-treated patients versus 24.3% of placebo-treated patients had ≥30% reduction in LFC using the efficacy estimand (P < 0.0001; treatment regimen estimand: 68.5% versus 28.6%, respectively; P < 0.0001). Mean percentage change in body weight was -12.2% with survodutide and -1.0% with placebo using the efficacy estimand (P < 0.0001; treatment regimen estimand: -8.7% versus -1.4%, respectively; P < 0.0001)." }, "verifiedAt": "2026-08-02" }, { "question": "Can a compounding pharmacy make survodutide?", "answer": "Not on the strength of anything this record can document, and the honest answer names what was checked and what was not. Section 503A permits compounding from a bulk drug substance only if it meets one of three conditions: it is the subject of an applicable USP or NF monograph, or it is a component of an FDA-approved drug product, or it appears on FDA's 503A bulks list. Two of the three were verified against primary documents on 2 August 2026 and both fail. Survodutide appears nowhere in FDA's list of bulk drug substances nominated for use in compounding under section 503A, updated 14 May 2026 — verified by fetching the PDF and extracting its text locally, with zero hits across all seven pages. And survodutide is not a component of any FDA-approved drug product, since Drugs@FDA returns no match for it at all. The third condition, whether an applicable USP or NF monograph exists, was not verified against a primary document and is not asserted here in either direction. Note also what does NOT apply: FDA's statement that retatrutide and cagrilintide 'cannot be used in compounding under federal law' appears on a page that does not mention survodutide anywhere, and it is not repeated here as though it did.", "source": { "url": "https://www.fda.gov/media/94155/download", "title": "Bulk Drug Substances Nominated for Use in Compounding Under Section 503A of the Federal Food, Drug, and Cosmetic Act", "publisher": "FDA", "date": "2026-05-14" }, "verifiedAt": "2026-08-02" } ] }, { "slug": "tb-500", "name": "TB-500", "aliases": [ "TB500", "Thymosin Beta-4 Fragment 17-23", "Ac-LKKTETQ", "N-acetylated heptapeptide LKKTETQ", "TB-500 acetate", "TB-500 (free base)" ], "url": "https://peptides101.com/compounds/tb-500", "moleculeNote": "TB-500 is NOT thymosin β4. TB-500 is a synthetic N-acetylated seven-amino-acid fragment (residues 17-23, LKKTETQ) of the full-length 43-amino-acid protein thymosin β4. FDA's 'no human exposure data' finding is scoped to the FRAGMENT — TB-500 (free base) and TB-500 acetate — and is accurate for that molecule. It is NOT a statement about full-length thymosin β4, which has a genuine multi-sponsor clinical programme in which the drug was administered to humans: RegeneRx/ReGenTree's RGN-259 ophthalmic solution (Tβ4 eye drops) reached Phase 3 for dry eye (NCT02974907, n=601, completed, results posted; NCT03937882 ARISE-3, n=700, completed), topical Tβ4 gel was tested in wound healing (NCT00832091, venous stasis ulcers, n=72, completed; NCT00311766, epidermolysis bullosa, n=30, TERMINATED for lack of patient availability and study-drug expiry), and Beijing Northland ran Phase 1a/1b of INTRAVENOUS recombinant human Tβ4 (NL005) in healthy volunteers (NCT04555824, n=54, completed; NCT04555850, n=30, completed). The caution the market elides: the full-length human programme is topical, ophthalmic and intravenous — none of it is IM/SC dosing of the acetylated fragment, which is what TB-500 was nominated and is sold for. A completed Phase 3 of Tβ4 eye drops, and a completed Phase 1 of IV recombinant Tβ4, are not human data for an injected seven-amino-acid fragment of a different molecule. Separately, on labelling: FDA documents that suppliers confuse the free base with the acetate — 'On several suppliers' websites, the CAS number for TB-500 (free base) (885340-08-9) is used for TB-500 Acetate.' That is a salt-form defect, and it is the one FDA actually found; we make no claim about what else is in the vial, because we have no analysis that would support one.", "quickAnswer": "TB-500 is not on FDA's 503A bulks list, so it may not lawfully be used in pharmacy compounding, and FDA staff proposed not adding TB-500 (free base) or TB-500 acetate to that list ahead of the Pharmacy Compounding Advisory Committee meeting on 23-24 July 2026, stating that they identified no clinical studies or human exposure data using TB-500 by any route of administration. TB-500 is a synthetic seven-amino-acid fragment (Ac-LKKTETQ) of the 43-amino-acid protein thymosin β4 and is not thymosin β4 itself — FDA states the two are not the same substance, so evidence about full-length thymosin β4 is not evidence about TB-500.", "fdaStatus": { "value": "not-approved", "note": "Not an FDA-approved drug for any indication, and not in active development toward approval. That says nothing about whether it is sold — it is.", "source": { "url": "https://www.fda.gov/media/193349/download", "title": "TB-500-Related Bulk Drug Substances — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, July 23-24, 2026", "publisher": "FDA", "date": "2026-07-23", "quote": "The nomination was withdrawn and FDA is evaluating the substances at its discretion." }, "verifiedAt": "2026-07-16" }, "compoundingStatus": { "value": "withdrawn-from-nomination", "note": "The single nomination — Wells Pharmacy Network, Document ID FDA-2015-N-3534-0304 — was withdrawn (withdrawal Document ID FDA-2015-N-3534-0484). Withdrawal did NOT stop the evaluation, and this is the fact that reconciles a 'withdrawn' status with an active staff proposal before the advisory committee on 23-24 July 2026: FDA writes that it 'has decided to evaluate both TB-500 (free base) and TB-500 acetate on its own initiative because it is unclear which substance the nominator intended to nominate.' So the substance is still being adjudicated despite the nominator walking away. Withdrawal is a nominator's act, not a legalisation event: TB-500 did not enter Category 1, it is not on the 503A bulks list, and it remains non-compoundable. Reporting that leaving Category 2 means access is coming has the direction backwards.", "source": { "url": "https://www.fda.gov/media/193349/download", "title": "TB-500-Related Bulk Drug Substances — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, July 23-24, 2026", "publisher": "FDA", "date": "2026-07-23", "quote": "The nomination was withdrawn and FDA is evaluating the substances at its discretion." }, "verifiedAt": "2026-07-16" }, "evidence": { "tier": "no-credible-evidence", "humanAdministrationChecked": true, "note": "Zero human administration of the fragment, and no positive nonclinical evidence for it either. FDA also writes: 'The nomination did not include, and FDA has not identified, any clinical studies or human exposure data using TB-500 via any ROA.' Two precisions matter more than the tier. (1) The animal wound-healing data is on a DIFFERENT PEPTIDE. In a 2003 study in aged mice, researchers reported that topical application of the NON-acetylated heptapeptide LKKTETQ increased epidermal closure and collagen content at the wound site (Philp et al. 2003). FDA's own caution: because acetylation irreversibly alters charge, hydrophobicity and size, 'the pharmacological profile of the non-acetylated heptapeptide LKKTETQ cannot be directly extrapolated to the N-acetylated heptapeptide TB-500.' TB-500 is the acetylated one. Limitations FDA notes: no dose-response assessment, and it is unknown whether the effect generalises to other wound types. (2) The only in-vitro study of TB-500 (free base) ITSELF was NEGATIVE — in a 2024 scratch assay in cultured fibroblasts, researchers reported wound closure was not significantly different between TB-500 (50 μg/mL) and vehicle; FDA writes that TB-500 'appeared to be devoid of wound-healing properties' (Rahaman et al. 2024), a study which itself lacks a concentration-response analysis. Reported in full, because it cuts against the marketing rather than for it: under the same conditions in that same study, a TB-500 METABOLITE, N-acetylated LKKTE, 'caused a small, but significant wound closure' — which is why FDA says it 'remains unknown whether TB-500 (free base) and TB-500 acetate could have wound-healing properties in vivo and, if so, whether their pharmacological activity depends on the conversion of the TB-500 moiety to a pharmacologically active metabolite.' A metabolite signal is a hypothesis about a mechanism, not evidence for the sold product. The evidence base for the substance sold under this name is borrowed from a molecule it is not.", "source": { "url": "https://www.fda.gov/media/193349/download", "title": "TB-500-Related Bulk Drug Substances — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, July 23-24, 2026", "publisher": "FDA", "date": "2026-07-23", "quote": "In conclusion, nonclinical pharmacological evidence is currently lacking to support the potential for TB-500 to promote wound healing, and nonclinical toxicological studies are not available to inform safety considerations for potential clinical uses of TB-500 (free base) or TB-500 acetate." }, "verifiedAt": "2026-07-16" }, "fdaApproval": null, "fdaFindings": [ { "finding": "FDA staff propose not adding TB-500 (free base) or TB-500 acetate to the 503A Bulks List, ahead of the Pharmacy Compounding Advisory Committee meeting on 23-24 July 2026.", "note": "A staff proposal is not a final determination. The briefing document states: 'The FDA will not issue a final determination on the issues at hand until input from the advisory committee process has been considered and all reviews have been finalized.'", "source": { "url": "https://www.fda.gov/media/193349/download", "title": "TB-500-Related Bulk Drug Substances — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, July 23-24, 2026", "publisher": "FDA", "date": "2026-07-23", "quote": "Accordingly, we propose not adding TB-500 (free base) or TB-500 acetate to the 503A Bulks List." }, "verifiedAt": "2026-07-16" }, { "finding": "FDA identified no human exposure data of any kind on TB-500 by any route of administration — no clinical studies, no pharmacokinetic or pharmacodynamic data, and no published case reports.", "note": "Read with the moleculeNote or this finding will be misquoted in both directions. It is TRUE and scoped to the 17-23 fragment. It is NOT a finding that thymosin β4 lacks human data — full-length Tβ4 has completed Phase 3 ophthalmic trials and completed Phase 1 intravenous trials. Anyone citing this line against Tβ4, or citing Tβ4's trials to rebut this line, has swapped the molecules.", "source": { "url": "https://www.fda.gov/media/193349/download", "title": "TB-500-Related Bulk Drug Substances — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, July 23-24, 2026", "publisher": "FDA", "date": "2026-07-23", "quote": "FDA is particularly concerned about the absence of human data on drug products containing these substances administered via any route of administration." }, "verifiedAt": "2026-07-16" }, { "finding": "TB-500 appears in no category of the 503A bulks list — not Category 1, 2 or 3 — and is not on the list of substances permitted for use in 503A compounding.", "note": "Verified by grepping the text-extracted document (updated 2026-05-14) directly for 'TB-500', 'TB500', 'thymosin' and 'beta-4': zero hits anywhere. Category 2 contains exactly six substances (Cesium Chloride, Domperidone, Germanium Sesquioxide, Ibutamoren Mesylate, Kisspeptin-10, Quinacrine HCl for intrauterine administration) and TB-500 is not among them. Note what this establishes and what it does not. It establishes the operative legal fact: TB-500 is not on the 503A bulks list, so it may not lawfully be used in 503A compounding for ANY use — that follows from absence from the list itself, not from the scope of FDA's evaluation. It does NOT establish WHY it is absent; this document cannot distinguish withdrawn from never-nominated. For the withdrawal, see legalStatus, which is sourced to the briefing document that states it.", "source": { "url": "https://www.fda.gov/media/94155/download", "title": "Bulk Drug Substances Nominated for Use in Compounding Under Section 503A of the Federal Food, Drug, and Cosmetic Act", "publisher": "FDA", "date": "2026-05-14" }, "verifiedAt": "2026-07-16" }, { "finding": "FDA found a lack of evidence to evaluate the effectiveness of TB-500 for its nominated use of wound healing, and identified no information anywhere in the medical literature in which TB-500 was administered to patients for any disease or condition. The nominator also never specified which wound type TB-500 is intended to treat.", "note": "This is an EVIDENTIARY VACUUM, NOT A REGULATORY LOOPHOLE. FDA never assessed whether TB-500 works for tendon, muscle or joint recovery — the uses it is actually marketed for — because the nomination was for wound healing and submitted no human data even for that. FDA states plainly: 'We note that the nominator has not provided information about what specific type of wound that TB-500 is intended to be used for.' 'FDA did not evaluate it for recovery' means nobody submitted evidence, not that the recovery claims survived scrutiny. On the nominator's own citations, note a tension inside the document rather than resolving it: footnote 43 states only 'The nominator cited three references in their nomination; three references are studies on Thymosin β4', while the body of the safety section describes two of the submitted articles (Philp et al. 2003; Shah et al. 2018) as 'nonclinical pharmacological studies of the non-acetylated heptapeptide LKKTETQ'. Either way the point stands and needs no inference: none of them is a study of TB-500 administered to humans.", "source": { "url": "https://www.fda.gov/media/193349/download", "title": "TB-500-Related Bulk Drug Substances — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, July 23-24, 2026", "publisher": "FDA", "date": "2026-07-23", "quote": "There is a lack of evidence to evaluate the effectiveness of TB-500 (free base) and TB-500 acetate products for the nominated use of wound healing. The nomination did not include, and FDA did not find any information in the medical literature where, TB-500 was administered to patients to treat any disease or condition including its use in wound healing." }, "verifiedAt": "2026-07-16" }, { "finding": "FDA defines TB-500 as a synthetic N-acetylated heptapeptide containing residues 17 through 23 (LKKTETQ) of the full-length 43-amino-acid peptide thymosin β4, and states directly that thymosin beta-4 and TB-500 are not the same substance, noting that seller websites use the two names interchangeably.", "note": "The two quoted sentences are from different sections, joined with an ellipsis: the definition opens section II.D.1.a (General Pharmacology of the Drug Substance) and the identity statement is footnote 35. Both are quoted verbatim, and the definition is here rather than only in the moleculeNote docblock because the quickAnswer asserts it — a docblock is a comment, not a Source, and cannot carry a claim. FDA files the second sentence as footnote 35, attached to the list of conditions TB-500 is marketed online for. The footnote is the whole argument of this record in FDA's own voice: the clinical programme buyers are implicitly relying on belongs to a 43-amino-acid protein, and the product is a seven-amino-acid acetylated fragment of it. FDA's evaluation is of the fragment and the conclusions are about the fragment.", "source": { "url": "https://www.fda.gov/media/193349/download", "title": "TB-500-Related Bulk Drug Substances — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, July 23-24, 2026", "publisher": "FDA", "date": "2026-07-23", "quote": "TB-500 is a synthetic N-acetylated heptapeptide containing the amino acid sequence 17 through 23 (LKKTETQ) of the full-length (43-amino acid) peptide thymosin β4. … Several websites state that TB-500 is a synthetic version of thymosin beta-4 and often use the terms interchangeably. However, as noted previously, thymosin beta-4 and TB-500 are not the same substance." }, "verifiedAt": "2026-07-16" }, { "finding": "TB-500 is not a United States Adopted Name, and FDA reports having encountered multiple salts and derivatives — including different active moieties — sold commercially under the TB-500 name. FDA treats that naming inconsistency as a safety risk in itself.", "note": "Read precisely, and note the restraint this record imposes on itself. FDA says it has encountered different active moieties sold under the TB-500 name; it does NOT say what those moieties are, how often, or that any of them is full-length thymosin β4, and we make no such claim — see the retraction note at the head of this file. What FDA does document concretely is the free base/acetate confusion: 'On several suppliers' websites, the CAS number for TB-500 (free base) (885340-08-9) is used for TB-500 Acetate.' The nomination package itself carried four separate identity inconsistencies — the CoA was for the acetate while the nominated substance was the free base, and the molecular formula given matched neither. FDA's conclusion is that both TB-500 (free base) and TB-500 acetate are 'not physically and chemically well characterized'.", "source": { "url": "https://www.fda.gov/media/193349/download", "title": "TB-500-Related Bulk Drug Substances — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, July 23-24, 2026", "publisher": "FDA", "date": "2026-07-23", "quote": "FDA has encountered multiple salts, and derivatives, including different active moieties, sold commercially under the same common name. Inconsistent naming conventions that do not follow established chemical nomenclature standards (e.g., INN, IUPAC, USAN) represent a safety risk for patients as they may be dosed with a different BDS than the physician ordered." }, "verifiedAt": "2026-07-16" }, { "finding": "No outsourcing facility has ever reported compounding a TB-500 drug product to FDA, and FDA found no pharmacy marketing one. FDA concluded the available data are too limited to understand TB-500's historical use in compounding at all.", "note": "The historical-use criterion is one of the four FDA balances, and TB-500 fails it for want of a record rather than on the merits: 'currently available data and published literature are too limited for FDA to understand the historical use of TB-500-related BDSs in compounded drug products.' Two facts sit underneath. TB-500 appears to have first been synthesised in 2003, and its first documented preparation was VETERINARY — FDA writes that 'a veterinary preparation of TB-500 appeared in 2011 and was marketed to boost performance in equine and greyhound sports (Ho et al. 2012).' The human market came after the animal-performance market, not after a clinical programme.", "source": { "url": "https://www.fda.gov/media/193349/download", "title": "TB-500-Related Bulk Drug Substances — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, July 23-24, 2026", "publisher": "FDA", "date": "2026-07-23", "quote": "No outsourcing facilities have reported compounding drug products containing TB-500 to FDA. Two websites were found that state that they obtain TB-500 from a compounding pharmacy, but no details were provided about the pharmacy from which the product is obtained; additionally, no pharmacies were found that market compounded drug products containing TB-500." }, "verifiedAt": "2026-07-16" }, { "finding": "TB-500 is not an approved drug anywhere FDA checked. There is no USP or NF monograph for TB-500 (free base) or TB-500 acetate, neither is a component of any FDA-approved drug, and there are no approved TB-500 products in ten other named countries or in the EU.", "note": "FDA states separately: 'There is no applicable United States Pharmacopeia (USP) or National Formulary (NF) drug substance monograph for TB-500 (free base) or its acetate form, and neither is a component of an FDA-approved drug.' This forecloses the common deflection that TB-500 is 'approved elsewhere' or 'pharmacopeial somewhere'. It is neither. Note the scope: FDA is speaking about TB-500, the fragment. Full-length thymosin β4 is likewise not an approved drug in the US, but that is a different substance with a different and genuinely clinical record — see moleculeNote.", "source": { "url": "https://www.fda.gov/media/193349/download", "title": "TB-500-Related Bulk Drug Substances — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, July 23-24, 2026", "publisher": "FDA", "date": "2026-07-23", "quote": "TB-500 is not recognized in either the European or Japanese Pharmacopeias. There are no approved products containing TB-500 in Canada, Australia, the United Kingdom, Belgium, Ireland, France, Norway, Germany, Spain, and Italy. Additionally, there are no products containing TB-500 that have been authorized for use in the European Union by the European Medicines Agency." }, "verifiedAt": "2026-07-16" }, { "finding": "TB-500 is on the World Anti-Doping Agency prohibited list under section S2.3, and was identified in a 2016 study of doping forums as one of the two most frequently discussed peptides and growth factors.", "note": "Prohibited-list status is an anti-doping fact, not an FDA safety or efficacy finding, and it should not be recruited as either — WADA prohibits substances for performance reasons regardless of whether they work as marketed. It is recorded because it is the operative fact for any tested athlete and it is checkable. FDA also notes WADA approved a project in 2013 to determine detection limits for TB-500's metabolites and implement them into peptide-screening methods. On the demand side, in a 2016 analysis of thirteen online doping forums, researchers reported that TB-500 was one of the two most frequently mentioned peptides and growth factors, emerging as a topic after 2010 with discussion trending upward since (Pineau et al. 2016). FDA's own framing of that study is a caution, not a corroboration: 'It is unclear whether the products discussed are compounded products or how the products are obtained.'", "source": { "url": "https://www.fda.gov/media/193349/download", "title": "TB-500-Related Bulk Drug Substances — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, July 23-24, 2026", "publisher": "FDA", "date": "2026-07-23", "quote": "TB-500 is on the list of prohibited substances under section S2.3 of the WADA." }, "verifiedAt": "2026-07-16" } ], "safetySignals": [ { "signal": "No FAERS reports and no published adverse-event cases were retrieved. Two reports in the Human Foods Complaint System concern 'blended TB-500 and BPC-157', but include no safety assessments.", "note": "An empty adverse-event database is NOT a safety finding, and reading it as one inverts the document. FDA's position is that risks are UNKNOWN, not absent: 'potential safety risks associated with the use of TB-500 in humans are unknown.' Absence of reports on a substance with zero human exposure data and voluntary reporting is uninformative — FDA attaches its standard FAERS limitations footnote for exactly this reason. The FAERS search ran through 26 March 2025; the HFCS search covered 1/1/2004 to 3/10/2025.", "source": { "url": "https://www.fda.gov/media/193349/download", "title": "TB-500-Related Bulk Drug Substances — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, July 23-24, 2026", "publisher": "FDA", "date": "2026-07-23" }, "verifiedAt": "2026-07-16" }, { "signal": "FDA flags a significant immunogenicity risk for TB-500 by the proposed intramuscular and subcutaneous routes, potentially amplified by aggregation and peptide-related impurities. No immunogenicity or aggregation studies were submitted or identified.", "note": "Note the burden as FDA frames it: 'The nomination did not include, and FDA has not identified, information about TB-500-related substances to suggest that these substances do not present such risks.' The route matters — this concern attaches to the injectable use TB-500 is sold for, and is not answered by full-length Tβ4's topical, ophthalmic and intravenous safety record, which is a different molecule.", "source": { "url": "https://www.fda.gov/media/193349/download", "title": "TB-500-Related Bulk Drug Substances — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, July 23-24, 2026", "publisher": "FDA", "date": "2026-07-23", "quote": "Peptides administered via injectable ROAs, such as the proposed IM and SC routes, may pose a significant risk for immunogenicity, potentially amplified by aggregation as well as potential peptide-related impurities." }, "verifiedAt": "2026-07-16" }, { "signal": "No nonclinical toxicity data: FDA identified no acute or repeat-dose toxicity studies, no nonclinical pharmacokinetic studies via the nominated intramuscular route, and no genotoxicity assessment for TB-500.", "note": "The gap runs deeper than the missing human data. FDA's conclusion is that 'nonclinical toxicological studies are not available to inform safety considerations for potential clinical uses of TB-500 (free base) or TB-500 acetate' — so the animal record cannot backstop the empty human record either. FDA did identify nonclinical PK studies showing TB-500 (free base) reaches the systemic circulation via the SC and IP routes and is hydrolysed into smaller peptides, but writes that it 'did not identify nonclinical PK studies in which animals received TB-500 (free base) or TB-500 acetate via the nominated IM ROA.'", "source": { "url": "https://www.fda.gov/media/193349/download", "title": "TB-500-Related Bulk Drug Substances — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, July 23-24, 2026", "publisher": "FDA", "date": "2026-07-23" }, "verifiedAt": "2026-07-16" } ], "faqs": [ { "question": "Is TB-500 legal in 2026?", "answer": "TB-500 is not an FDA-approved drug, is not a component of any FDA-approved drug, and has no United States Pharmacopeia or National Formulary drug substance monograph — and it is not on FDA's 503A bulks list of substances that may be used in pharmacy compounding, which is why a 503A pharmacy may not lawfully compound it for any use. FDA staff proposed not adding TB-500 (free base) or TB-500 acetate to that list ahead of the Pharmacy Compounding Advisory Committee meeting on 23-24 July 2026. Separately from US drug law, TB-500 is on the World Anti-Doping Agency prohibited list under section S2.3, so it is banned for tested athletes.", "source": { "url": "https://www.fda.gov/media/193349/download", "title": "TB-500-Related Bulk Drug Substances — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, July 23-24, 2026", "publisher": "FDA", "date": "2026-07-23", "quote": "There is no applicable United States Pharmacopeia (USP) or National Formulary (NF) drug substance monograph for TB-500 (free base) or its acetate form, and neither is a component of an FDA-approved drug. … Accordingly, we propose not adding TB-500 (free base) or TB-500 acetate to the 503A Bulks List." }, "verifiedAt": "2026-07-16" }, { "question": "Did TB-500 become legal again when the FDA nomination was withdrawn?", "answer": "No. The single nomination for TB-500 — submitted by Wells Pharmacy Network — was withdrawn by the nominator, and a nominator withdrawing is not an FDA decision, an approval, or a legalisation event. TB-500 did not move onto the 503A bulks list; it is absent from that list entirely, which is what makes it non-compoundable. The withdrawal did not even stop the review: FDA states it decided to evaluate both TB-500 (free base) and TB-500 acetate on its own initiative, and its staff proposed not adding either to the list ahead of the Pharmacy Compounding Advisory Committee meeting on 23-24 July 2026.", "source": { "url": "https://www.fda.gov/media/193349/download", "title": "TB-500-Related Bulk Drug Substances — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, July 23-24, 2026", "publisher": "FDA", "date": "2026-07-23", "quote": "The nomination was withdrawn and FDA is evaluating the substances at its discretion." }, "verifiedAt": "2026-07-16" }, { "question": "Is TB-500 the same thing as thymosin beta-4?", "answer": "No. FDA states that thymosin beta-4 and TB-500 are not the same substance, and notes that seller websites use the two names interchangeably. TB-500 is a synthetic N-acetylated seven-amino-acid fragment — residues 17 through 23, LKKTETQ — of the full-length 43-amino-acid protein thymosin β4. The distinction decides what the evidence means: FDA identified no clinical studies and no human exposure data for TB-500 itself by any route of administration, and because thymosin β4 is a different substance, evidence about thymosin β4 is not evidence about TB-500. FDA also cautions that because acetylation irreversibly alters a peptide's charge, hydrophobicity and size, the profile of the non-acetylated heptapeptide LKKTETQ cannot be directly extrapolated to the N-acetylated heptapeptide TB-500.", "source": { "url": "https://www.fda.gov/media/193349/download", "title": "TB-500-Related Bulk Drug Substances — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, July 23-24, 2026", "publisher": "FDA", "date": "2026-07-23", "quote": "Several websites state that TB-500 is a synthetic version of thymosin beta-4 and often use the terms interchangeably. However, as noted previously, thymosin beta-4 and TB-500 are not the same substance." }, "verifiedAt": "2026-07-16" }, { "question": "Is there any human evidence that TB-500 works?", "answer": "No. FDA conducted a literature search and reported that no articles were found in which TB-500 was administered to humans — no clinical studies, no pharmacokinetic or pharmacodynamic data by any route, and no case reports. The nonclinical record does not fill the gap either: FDA concluded that nonclinical pharmacological evidence is currently lacking to support the potential for TB-500 to promote wound healing, and the only in-vitro study of TB-500 itself was negative — in a 2024 scratch assay in cultured fibroblasts, researchers reported wound closure was not significantly different between TB-500 and vehicle (Rahaman et al. 2024). The animal wound-healing data cited for TB-500 is on a different peptide, the non-acetylated heptapeptide LKKTETQ, which FDA says cannot be directly extrapolated to TB-500.", "source": { "url": "https://www.fda.gov/media/193349/download", "title": "TB-500-Related Bulk Drug Substances — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, July 23-24, 2026", "publisher": "FDA", "date": "2026-07-23", "quote": "After conducting a literature search, no articles were found in which TB-500 was administered to humans." }, "verifiedAt": "2026-07-16" }, { "question": "Can I get TB-500 from a compounding pharmacy?", "answer": "Not lawfully. TB-500 is not on FDA's 503A bulks list, so a 503A compounding pharmacy may not use it to compound a drug product for any use, and FDA reported that no outsourcing facility has ever told FDA it compounds a TB-500 product and that it found no pharmacy marketing one. FDA did find two websites claiming to obtain TB-500 from a compounding pharmacy, but they named no pharmacy. FDA also found several websites selling TB-500 powder for reconstitution which state that the products are intended for research use only.", "source": { "url": "https://www.fda.gov/media/193349/download", "title": "TB-500-Related Bulk Drug Substances — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, July 23-24, 2026", "publisher": "FDA", "date": "2026-07-23", "quote": "No outsourcing facilities have reported compounding drug products containing TB-500 to FDA. Two websites were found that state that they obtain TB-500 from a compounding pharmacy, but no details were provided about the pharmacy from which the product is obtained; additionally, no pharmacies were found that market compounded drug products containing TB-500." }, "verifiedAt": "2026-07-16" }, { "question": "What did FDA propose at the July 2026 PCAC meeting about TB-500?", "answer": "FDA staff proposed not adding TB-500 (free base) or TB-500 acetate to the 503A bulks list, in a briefing document dated 15 May 2026 prepared for the Pharmacy Compounding Advisory Committee meeting on 23-24 July 2026. FDA's stated basis was the lack of data on physicochemical characterisation, the lack of historical use in compounding, the non-existent information on these substances administered in humans, and the risk that peptides given by the proposed intramuscular and subcutaneous routes may pose for immunogenicity, together with the existence of FDA-approved therapies for wounds. A staff proposal is not a final determination: the document states FDA will not issue one until the advisory committee input has been considered and all reviews finalised.", "source": { "url": "https://www.fda.gov/media/193349/download", "title": "TB-500-Related Bulk Drug Substances — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, July 23-24, 2026", "publisher": "FDA", "date": "2026-07-23", "quote": "On balance, the physiochemical characterization, information on historical use, lack of any evidence of effectiveness, and safety information for both TB-500 (free base) and TB-500 acetate weigh against their being added to the 503A Bulks List." }, "verifiedAt": "2026-07-16" }, { "question": "Is TB-500 safe?", "answer": "Unknown, and FDA says so explicitly rather than reassuringly: its position is that potential safety risks associated with the use of TB-500 in humans are unknown, because there is no human data on it by any route. That is not a clean safety record. FDA identified no acute toxicity, repeat-dose toxicity, genotoxicity, carcinogenicity, or developmental and reproductive toxicity studies of TB-500 (free base) or TB-500 acetate, so the animal record cannot backstop the empty human record. FDA flags that peptides given by the proposed intramuscular and subcutaneous routes may pose a significant risk for immunogenicity, potentially amplified by aggregation and peptide-related impurities, and notes that the nomination included no information suggesting these substances do not present such risks. A search of FAERS through 26 March 2025 retrieved no reports, which is uninformative for a substance with no documented human exposure and voluntary reporting.", "source": { "url": "https://www.fda.gov/media/193349/download", "title": "TB-500-Related Bulk Drug Substances — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, July 23-24, 2026", "publisher": "FDA", "date": "2026-07-23", "quote": "The nomination did not include, and FDA has not identified, any clinical studies or human exposure data using TB-500 via any ROA. Therefore, potential safety risks associated with the use of TB-500 in humans are unknown." }, "verifiedAt": "2026-07-16" } ] }, { "slug": "teriparatide", "name": "Teriparatide", "aliases": [ "Forteo", "Bonsity", "PTH(1-34)", "rhPTH(1-34)", "recombinant human parathyroid hormone (1-34)", "teriparatide acetate", "Parathar" ], "url": "https://peptides101.com/compounds/teriparatide", "moleculeNote": "A recombinant human parathyroid hormone analog. The FORTEO label describes it as 'a recombinant human parathyroid hormone analog (PTH 1-34)' with 'an identical sequence to the 34 N-terminal amino acids (the biologically active region) of the 84-amino acid human parathyroid hormone', manufactured in a modified strain of Escherichia coli. Three disambiguations matter and all three are live in this market. (1) Teriparatide is the 1-34 FRAGMENT, not full-length PTH(1-84) — a different molecule with its own separate regulatory history that this record does not cover. (2) SALT FORM. The approved FORTEO product contains teriparatide as a free base, per the label's DESCRIPTION section. Drugs@FDA separately lists PARATHAR (NDA 019498, Sanofi Aventis US), whose active ingredient it records as TERIPARATIDE ACETATE and whose marketing status it records as Discontinued. The alias list above includes both because both are called teriparatide, not because they are the same product. (3) Material sold as 'PTH 1-34' outside the approved products is not identified by sequence alone: nothing in the documents read for this record establishes what is in such a vial, and this record makes no claim about it in either direction.", "quickAnswer": "Teriparatide is FDA-approved, as the active ingredient in FORTEO (NDA 021318, Eli Lilly and Company, approved 2002-11-26) and in four later applications Drugs@FDA lists — BONSITY (NDA 211939) and three generic teriparatide injections. The FORTEO label carries three indications, all of them second-line on their face: treatment of postmenopausal women with osteoporosis, increasing bone mass in men with primary or hypogonadal osteoporosis, and treatment of men and women with osteoporosis associated with sustained systemic glucocorticoid therapy — each restricted to patients 'at high risk for fracture or who have failed or are intolerant to other available osteoporosis therapy'. FORTEO no longer carries a boxed warning: it had one for rat osteosarcoma from its original 2002 labeling until FDA approved supplement S-054 on 2020-11-16, a supplement the approval letter says provides for 'Removal of the Boxed Warning regarding osteosarcoma'. Osteosarcoma remains in the current label as a Warning and Precaution, which states that osteosarcoma has been reported in FORTEO-treated patients post-marketing while an increased risk has not been observed in observational studies in humans; two claims-based surveillance studies reported in the label identified three and zero osteosarcoma cases among 379,283 and 153,316 FORTEO users, results the label says suggest a similar risk between FORTEO users and their comparators but whose interpretation 'calls for caution' given data-source limitations. Teriparatide appears in none of Categories 1, 2 or 3 of FDA's 503A bulk drug substances list updated 2026-05-14.", "fdaStatus": { "value": "approved", "note": "FDA-approved, and approved more than once: Drugs@FDA returns five applications with teriparatide as an active ingredient, recorded with their own source under fdaFindings. Approval is always for a specific indication and population, and here the population gating is unusually tight — see the approval record below, where every one of the three indications is restricted to patients at high risk for fracture or who have failed or are intolerant to other available osteoporosis therapy. Teriparatide is a second-line drug on its own label.", "source": { "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/021318s057lbl.pdf", "title": "FORTEO (teriparatide injection) — Full Prescribing Information", "publisher": "FDA", "date": "2024-07-26", "quote": "FORTEO (teriparatide injection), for subcutaneous use … FORTEO is a parathyroid hormone analog, (PTH 1-34), indicated for: • Treatment of postmenopausal women with osteoporosis at high risk for fracture or patients who have failed or are intolerant to other available osteoporosis therapy (1)" }, "verifiedAt": "2026-08-02" }, "compoundingStatus": null, "evidence": { "tier": "proven-in-humans", "humanAdministrationChecked": true, "note": "Administration check RUN, not assumed. The Neer 2001 record was opened on 2026-08-02: 1637 postmenopausal women with prior vertebral fractures were randomly assigned to receive parathyroid hormone (1-34) or placebo, ADMINISTERED SUBCUTANEOUSLY by the participants themselves. The drug was given to people. It was not measured as an endogenous biomarker — the trap that reduces MOTS-c and TB-500 from an apparent five human RCTs to an actual zero, and a trap this compound is unusually exposed to, since parathyroid hormone is an endogenous hormone that appears in thousands of papers as an assay result rather than an intervention. THE TRIALS, NAMED. Three are described in section 14 of the FORTEO label and all three were read there: (14.1) the trial published as Neer 2001, double-blind, multicenter, placebo-controlled, 1637 postmenopausal women with osteoporosis; (14.2) a double-blind, multicenter, placebo-controlled trial of 437 men with primary (idiopathic) or hypogonadal osteoporosis; (14.3) a randomized, double-blind, ACTIVE-controlled trial of 428 patients with glucocorticoid-induced osteoporosis, 19% men and 81% women, aged 22 to 89 years, of 18 months' duration. A DISCREPANCY WORTH RECORDING because it is the kind of thing that gets flattened: the label reports a median EXPOSURE of 19 months for 14.1, while the publication reports a median duration of OBSERVATION of 21 months. Those are different quantities and neither document is wrong. SCOPE, and it is narrow. The tier attaches to the approved products and to the three approved indications. Only 14.1 carried fracture endpoints; the label states the primary efficacy endpoint of 14.2 was change in lumbar spine bone mineral density, and 14.3 is reported on bone mineral density, with the label stating that active-comparator data are not presented because of 'differences in mechanism of action (anabolic vs. anti-resorptive) and lack of clarity regarding differences in BMD as an adequate predictor of fracture efficacy'. Fracture-reduction evidence and bone-density evidence are not the same evidence, and the label does not treat them as such. Nothing here transfers to unapproved material sold as 'PTH 1-34'.", "source": { "url": "https://pubmed.ncbi.nlm.nih.gov/11346808/", "title": "Effect of parathyroid hormone (1-34) on fractures and bone mineral density in postmenopausal women with osteoporosis (Neer RM, Arnaud CD, Zanchetta JR, et al.)", "publisher": "PubMed", "date": "2001-05-10" }, "verifiedAt": "2026-08-02" }, "fdaApproval": { "applicationNumber": "NDA 021318 (FORTEO, Eli Lilly and Company; approved 2002-11-26)", "brandName": "Forteo", "approvedIndication": "FORTEO is indicated: • For the treatment of postmenopausal women with osteoporosis at high risk for fracture (defined herein as having a history of osteoporotic fracture or multiple risk factors for fracture) or who have failed or are intolerant to other available osteoporosis therapy. In postmenopausal women with osteoporosis, FORTEO reduces the risk of vertebral and nonvertebral fractures. • To increase bone mass in men with primary or hypogonadal osteoporosis at high risk for fracture or who have failed or are intolerant to other available osteoporosis therapy. • For the treatment of men and women with osteoporosis associated with sustained systemic glucocorticoid therapy … at high risk for fracture or who have failed or are intolerant to other available osteoporosis therapy.", "discontinued": false, "discontinuedNote": "FORTEO is marketed, so this is false — but Drugs@FDA records TWO products under NDA 021318 and only one of them is current: the smaller-volume prefilled pen carries marketing status Prescription, and the larger-volume presentation carries marketing status Discontinued. 'Forteo is discontinued' and 'a Forteo presentation is discontinued' are different statements and the second one is the true one.", "source": { "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/021318s057lbl.pdf", "title": "FORTEO (teriparatide injection) — Full Prescribing Information", "publisher": "FDA", "date": "2024-07-26", "quote": "FORTEO is indicated: • For the treatment of postmenopausal women with osteoporosis at high risk for fracture (defined herein as having a history of osteoporotic fracture or multiple risk factors for fracture) or who have failed or are intolerant to other available osteoporosis therapy. In postmenopausal women with osteoporosis, FORTEO reduces the risk of vertebral and nonvertebral fractures. • To increase bone mass in men with primary or hypogonadal osteoporosis at high risk for fracture or who have failed or are intolerant to other available osteoporosis therapy. • For the treatment of men and women with osteoporosis associated with sustained systemic glucocorticoid therapy … at high risk for fracture or who have failed or are intolerant to other available osteoporosis therapy." }, "verifiedAt": "2026-08-02" }, "fdaFindings": [ { "finding": "FDA approved NDA 021318 supplement S-054 on 2020-11-16. The supplement approval letter states that the supplemental application provides for removal of the Boxed Warning regarding osteosarcoma; modification of the Recommended Treatment Duration section to allow for longer duration of treatment in patients who remain at or return to having a high risk for fracture; addition of the risk of cutaneous calcification including calciphylaxis to the existing warning regarding hypercalcemia and hypercalcemic disorders; and revision of the Postmarketing Experience section to reflect the findings from the long-term osteosarcoma surveillance studies.", "note": "The single most useful document on this record, and it runs against the direction this site's findings usually run: a regulator making a label LESS restrictive on the strength of accumulated human data. Read the letter's own structure, because it is not a one-way relaxation — item (c) ADDS a risk (calciphylaxis and cutaneous calcification) at the same time item (a) removes the boxed warning. FDA traded a rodent-derived warning for a human-derived one. This entry is the source for a claim made nowhere else in this library, so it is quoted at length rather than summarised: the boxed warning is GONE. Any page still describing Forteo as a black-box drug is describing the label as it stood before 16 November 2020. Cross-checked directly against the current labeling — the 2024 prescribing information (S-057) contains zero case-insensitive matches for 'boxed warning', and the SPL served by openFDA carries no boxed-warning section at all.", "source": { "url": "https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2020/021318Orig1s054ltr.pdf", "title": "NDA 021318/S-054 Supplement Approval Letter — Forteo (teriparatide injection)", "publisher": "FDA", "date": "2020-11-16", "quote": "This Prior Approval supplemental new drug application provides for: a. Removal of the Boxed Warning regarding osteosarcoma. b. Modification of Section 2.3 (Dosage and Administration, Recommended Treatment Duration) to allow for longer duration of treatment in patients who remain at or return to having a high risk for fracture. c. Addition of the risk of cutaneous calcification including calciphylaxis to the existing warning regarding hypercalcemia and hypercalcemic disorders d. Revision of Section 6.3 (Adverse Reactions, Postmarketing Experience) to reflect the findings from the long-term osteosarcoma surveillance studies." }, "verifiedAt": "2026-08-02" }, { "finding": "The original FORTEO labeling approved in 2002 carried a boxed warning stating that in male and female rats, teriparatide caused an increase in the incidence of osteosarcoma (a malignant bone tumor) that was dependent on dose and treatment duration, and that because of the uncertain relevance of the rat osteosarcoma finding to humans, teriparatide should be prescribed only to patients for whom the potential benefits are considered to outweigh the potential risk. That boxed warning was removed by supplement S-054, approved 2020-11-16.", "note": "Recorded to make the removal checkable in both directions. A claim that something was removed is only as good as the evidence it was ever there, and 'everyone knows Forteo had a black box' is not evidence — so the superseded 2002 labeling is cited directly. The document carries Lilly's own notice that 'This label may not be the latest approved by FDA', and it is used here for exactly that reason: it is the historical record, not the current one, and this record never presents it as current. QUOTE HANDLING: one sentence is elided, marked with an ellipsis. It expressed the rat exposures as multiples of a specific human microgram dose, which is an amount, so it is removed under this site's no-dosing policy. The finding — rat osteosarcoma, dependent on dose and treatment duration, of uncertain human relevance — is intact.", "source": { "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2002/21318_forteo_lbl.pdf", "title": "FORTEO (teriparatide) injection — original approved labeling, NDA 21-318 (superseded)", "publisher": "FDA", "date": "2002-11-26", "quote": "WARNING In male and female rats, teriparatide caused an increase in the incidence of osteosarcoma (a malignant bone tumor) that was dependent on dose and treatment duration. … Because of the uncertain relevance of the rat osteosarcoma finding to humans, teriparatide should be prescribed only to patients for whom the potential benefits are considered to outweigh the potential risk." }, "verifiedAt": "2026-08-02" }, { "finding": "Drugs@FDA lists five applications with teriparatide as an active ingredient: NDA 021318 (FORTEO, Eli Lilly and Company, approved 2002-11-26); NDA 211939 (BONSITY, Alvogen, approved 2019-10-04); and three abbreviated new drug applications for teriparatide injection — ANDA 208569 (Teva Pharmaceuticals USA, approved 2023-11-16), ANDA 211097 (Apotex, approved 2023-11-16) and ANDA 213641 (Amphastar Pharmaceuticals, approved 2025-12-12). Drugs@FDA records the marketing status of a product under each of the five as Prescription.", "note": "Recorded because 'teriparatide' does not identify a product, and because the ANDAs are the part people miss. An abbreviated new drug application is the generic pathway: three of these five applications exist because FDA accepted teriparatide injection as a drug capable of having generics, which is a materially different regulatory posture from the protein therapeutics this category is usually compared to. Approval dates are the ORIG submission status dates in the same Drugs@FDA response. What this entry does NOT establish: it says nothing about relative price, about substitutability at the pharmacy counter, or about whether any given product is on the shelf today. Marketing status in Drugs@FDA is an application-level record, not a supply report.", "source": { "url": "https://api.fda.gov/drug/drugsfda.json?search=openfda.generic_name:%22teriparatide%22&limit=20", "title": "Drugs@FDA — applications with teriparatide as an active ingredient (openFDA drug/drugsfda)", "publisher": "FDA", "date": "2026-07-31" }, "verifiedAt": "2026-08-02" }, { "finding": "The current FORTEO label states in its Highlights header 'Initial U.S. Approval: 1987', which is fifteen years earlier than the 2002-11-26 approval of NDA 021318. Drugs@FDA separately lists NDA 019498 (PARATHAR, Sanofi Aventis US), whose active ingredient it records as TERIPARATIDE ACETATE and whose marketing status it records as Discontinued.", "note": "Two verified observations, deliberately left unjoined. The 1987 date is on the label and the discontinued acetate application is in Drugs@FDA, and it is tempting to say the first refers to the second — but no document read for this record says so, and openFDA returns no submission history for NDA 019498, so its approval date could not be confirmed here. Writing the causal sentence would be a guess, and a guess is fatal. What follows regardless, and is the reason this is recorded at all: 'Initial U.S. Approval' on a label is a statement about the ACTIVE MOIETY, not about the product in front of you. Anyone citing 1987 as Forteo's approval date is citing the wrong application by fifteen years, and anyone treating a discontinued acetate product as evidence about the marketed free-base product is making the salt-form error this site documents at length elsewhere. GAP, stated plainly: the indication, sponsor history and reason for discontinuation of NDA 019498 were not established and are not asserted.", "source": { "url": "https://api.fda.gov/drug/drugsfda.json?search=openfda.generic_name:%22teriparatide%22&limit=20", "title": "Drugs@FDA — applications with teriparatide as an active ingredient (openFDA drug/drugsfda)", "publisher": "FDA", "date": "2026-07-31" }, "verifiedAt": "2026-08-02" }, { "finding": "Teriparatide appears in none of Categories 1, 2 or 3 of FDA's list of bulk drug substances nominated for use in compounding under section 503A, updated 2026-05-14.", "note": "Recorded to close a misreading, not to assert a status — which is why this record carries NO compoundingStatus field at all. Verified by fetching the document with a browser user-agent and text-extracting all seven pages on 2026-08-02: zero hits for 'teriparatide', zero for 'parathyroid', zero for 'PTH'. Absence from this list is not a category and not a finding. It cannot distinguish 'nominated then withdrawn' from 'never nominated' from 'approved drug that was never on the nomination track at all', and teriparatide is squarely in that third situation: a 503A bulks nomination is a route for substances that lack an approved product, and teriparatide is the active ingredient in five approved applications. Recording it as 'never-nominated' would imply a proceeding it was never part of, so the field is omitted instead. SCOPE: this entry is about one document. It is not an answer to whether a pharmacy may lawfully compound a teriparatide preparation — that turns on other parts of section 503A, including the essentially-a-copy restriction, and no document read for this record addresses it.", "source": { "url": "https://www.fda.gov/media/94155/download", "title": "Bulk Drug Substances Nominated for Use in Compounding Under Section 503A of the Federal Food, Drug, and Cosmetic Act", "publisher": "FDA", "date": "2026-05-14" }, "verifiedAt": "2026-08-02" } ], "safetySignals": [ { "signal": "Warnings and Precautions, section 5.1 — Osteosarcoma. The label states that an increase in the incidence of osteosarcoma (a malignant bone tumor) was observed in male and female rats treated with teriparatide; that osteosarcoma has been reported in patients treated with FORTEO in the post marketing setting; that an increased risk of osteosarcoma has not been observed in observational studies in humans; and that there are limited data assessing the risk of osteosarcoma beyond 2 years of FORTEO use. The label directs that FORTEO be avoided in patients at increased baseline risk of osteosarcoma: those with open epiphyses (pediatric and young adult patients), metabolic bone diseases other than osteoporosis including Paget's disease of the bone, bone metastases or a history of skeletal malignancies, prior external beam or implant radiation therapy involving the skeleton, and hereditary disorders predisposing to osteosarcoma.", "note": "The osteosarcoma signal did not disappear when the box did — it was RELOCATED to Warnings and Precautions, and both halves of that sentence are load-bearing. This single paragraph holds three claims that are routinely quoted one at a time by people arguing opposite conclusions: rats got tumors; humans on the drug have been reported to get tumors post-marketing; observational studies in humans have not shown an increased risk. All three are in the same paragraph of the same label. The label also states the data beyond 2 years of use are limited, which is a stated gap rather than a reassurance. The avoid-in list is a screening conversation a prescriber has and a purchaser of unapproved material is never asked.", "source": { "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/021318s057lbl.pdf", "title": "FORTEO (teriparatide injection) — Full Prescribing Information", "publisher": "FDA", "date": "2024-07-26", "quote": "An increase in the incidence of osteosarcoma (a malignant bone tumor) was observed in male and female rats treated with teriparatide. Osteosarcoma has been reported in patients treated with FORTEO in the post marketing setting; however, an increased risk of osteosarcoma has not been observed in observational studies in humans. There are limited data assessing the risk of osteosarcoma beyond 2 years of FORTEO use" }, "verifiedAt": "2026-08-02" }, { "signal": "Adverse Reactions, section 6.3 — the postmarketing osteosarcoma surveillance data. The label reports that two osteosarcoma surveillance safety studies, both U.S. claims-based database studies, were designed to obtain data on the incidence rate of osteosarcoma among FORTEO-treated patients, and that three and zero osteosarcoma cases respectively were identified among 379,283 and 153,316 FORTEO users. The label states the study results suggest a similar risk for osteosarcoma between FORTEO users and their comparators, and that interpretation calls for caution owing to the limitations of the data sources, which do not allow for complete measurement and control for confounders.", "note": "This is the evidence the boxed-warning removal rests on, and the letter approving that removal names it: item (d) of NDA 021318/S-054 provides for revising this very section 'to reflect the findings from the long-term osteosarcoma surveillance studies'. Half a million treated patients across two claims-based studies is a real denominator, which is more than almost anything else on this site has. Read FDA's own caveat rather than the headline: the label states the interpretation 'calls for caution owing to the limitations of the data sources which do not allow for complete measurement and control for confounders'. Claims-database studies are not trials. A finding of similar risk is not a finding of no risk, and it does not erase the post-marketing case reports recorded in the same section.", "source": { "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/021318s057lbl.pdf", "title": "FORTEO (teriparatide injection) — Full Prescribing Information", "publisher": "FDA", "date": "2024-07-26", "quote": "In these two studies, three and zero osteosarcoma cases were identified among 379,283 and 153,316 FORTEO users, respectively. The study results suggest a similar risk for osteosarcoma between FORTEO users and their comparators. However, the interpretation of the study results calls for caution owing to the limitations of the data sources which do not allow for complete measurement and control for confounders." }, "verifiedAt": "2026-08-02" }, { "signal": "Warnings and Precautions, section 5.2 — Hypercalcemia and Cutaneous Calcification. The label states that FORTEO has not been studied in patients with pre-existing hypercalcemia, may cause hypercalcemia and may exacerbate hypercalcemia in patients with pre-existing hypercalcemia, and should be avoided in patients known to have an underlying hypercalcemic disorder such as primary hyperparathyroidism. It further states that serious reports of calciphylaxis and worsening of previously stable cutaneous calcification have been reported in the post-marketing setting in patients taking FORTEO, that risk factors for development of calciphylaxis include underlying auto-immune disease, kidney failure, and concomitant warfarin or systemic corticosteroid use, and that FORTEO should be discontinued in patients who develop calciphylaxis or worsening of previously stable cutaneous calcification.", "note": "The risk FDA ADDED in the same action that removed the boxed warning — item (c) of the S-054 supplement approval letter. Recorded next to the removal deliberately, because a page that reports only the removal reports half of what FDA did. Note the risk factors: warfarin and systemic corticosteroids are common co-medications, and systemic glucocorticoid therapy is the defining feature of the population in the third approved indication.", "source": { "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/021318s057lbl.pdf", "title": "FORTEO (teriparatide injection) — Full Prescribing Information", "publisher": "FDA", "date": "2024-07-26", "quote": "Serious reports of calciphylaxis and worsening of previously stable cutaneous calcification have been reported in the post-marketing setting in patients taking FORTEO. Risk factors for development of calciphylaxis include underlying auto-immune disease, kidney failure, and concomitant warfarin or systemic corticosteroid use. Discontinue FORTEO in patients who develop calciphylaxis or worsening of previously stable cutaneous calcification." }, "verifiedAt": "2026-08-02" }, { "signal": "Warnings and Precautions, section 5.4 — Orthostatic Hypotension. The label states that in short-term clinical pharmacology studies of FORTEO in healthy volunteers, transient episodes of symptomatic orthostatic hypotension were observed in 5% of volunteers; that these events typically began within 4 hours of dosing and resolved without treatment within a few minutes to a few hours; that when transient orthostatic hypotension occurred it happened within the first several doses, was relieved by placing the person in a reclining position, and did not preclude continued treatment; and that FORTEO should be administered initially under circumstances in which the patient can sit or lie down if symptoms occur. Section 5.3 separately directs that the risks and benefits be considered in patients with active or recent urolithiasis because of the potential to exacerbate this condition, the label noting that FORTEO has not been studied in patients with active urolithiasis.", "note": "Included because it is the labeled risk with an ADMINISTRATION-SETTING instruction attached, and that instruction is the one that silently disappears outside a prescribing relationship. The label's own framing is notably undramatic — transient, self-resolving, early, not a reason to stop — which is exactly why it is recorded verbatim rather than characterised.", "source": { "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/021318s057lbl.pdf", "title": "FORTEO (teriparatide injection) — Full Prescribing Information", "publisher": "FDA", "date": "2024-07-26", "quote": "In short-term clinical pharmacology studies of FORTEO in healthy volunteers, transient episodes of symptomatic orthostatic hypotension were observed in 5% of volunteers." }, "verifiedAt": "2026-08-02" }, { "signal": "Contraindication — the label states that FORTEO is contraindicated in patients with hypersensitivity to teriparatide or to any of its excipients, and that hypersensitivity reactions have included angioedema and anaphylaxis. The Postmarketing Experience section lists anaphylactic reactions, drug hypersensitivity, angioedema and urticaria among adverse reactions identified during postapproval use, and states that hypercalcemia greater than 13 mg/dL has been reported with FORTEO use.", "note": "The label attaches its own caveat to everything in the postmarketing list: 'Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.' Spontaneous reports are a floor of unknown height, not a rate. The 13 mg/dL figure is a reported laboratory VALUE, not a dose.", "source": { "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/021318s057lbl.pdf", "title": "FORTEO (teriparatide injection) — Full Prescribing Information", "publisher": "FDA", "date": "2024-07-26", "quote": "FORTEO is contraindicated in patients with hypersensitivity to teriparatide or to any of its excipients. Hypersensitivity reactions have included angioedema and anaphylaxis" }, "verifiedAt": "2026-08-02" } ], "faqs": [ { "question": "Does Forteo (teriparatide) still have a black box warning?", "answer": "No. FDA removed it. The approval letter for NDA 021318 supplement S-054 states that the supplemental application provides for, first on its list, 'Removal of the Boxed Warning regarding osteosarcoma.' Drugs@FDA records that supplement as approved on 16 November 2020. The current FORTEO prescribing information — the 2024 labeling approved under supplement S-057 — contains no boxed warning at all, and neither does the current structured product label. The risk was not deleted from the label, it was moved: osteosarcoma now appears as Warning and Precaution 5.1. And the same supplement that removed the box ADDED a warning, for cutaneous calcification including calciphylaxis, alongside the existing hypercalcemia warning. Any source describing teriparatide as a black-box drug is describing the label as it stood before 16 November 2020.", "source": { "url": "https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2020/021318Orig1s054ltr.pdf", "title": "NDA 021318/S-054 Supplement Approval Letter — Forteo (teriparatide injection)", "publisher": "FDA", "date": "2020-11-16", "quote": "This Prior Approval supplemental new drug application provides for: a. Removal of the Boxed Warning regarding osteosarcoma." }, "verifiedAt": "2026-08-02" }, { "question": "What is teriparatide FDA-approved to treat?", "answer": "Osteoporosis, in three specific populations, and in every one of them only as a second-line option. The FORTEO label indicates it for the treatment of postmenopausal women with osteoporosis at high risk for fracture — defined in the label as having a history of osteoporotic fracture or multiple risk factors for fracture — or who have failed or are intolerant to other available osteoporosis therapy; to increase bone mass in men with primary or hypogonadal osteoporosis at high risk for fracture or who have failed or are intolerant to other available osteoporosis therapy; and for the treatment of men and women with osteoporosis associated with sustained systemic glucocorticoid therapy at high risk for fracture or who have failed or are intolerant to other available osteoporosis therapy. Read the qualifier, because it is in all three: FDA did not approve teriparatide for osteoporosis generally, for low bone density, for bone healing, or for anything a person without osteoporosis would recognise as a goal. The label's own efficacy claim is likewise confined — it states that in postmenopausal women with osteoporosis, FORTEO reduces the risk of vertebral and nonvertebral fractures, and it makes that fracture claim for no other population.", "source": { "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/021318s057lbl.pdf", "title": "FORTEO (teriparatide injection) — Full Prescribing Information", "publisher": "FDA", "date": "2024-07-26", "quote": "FORTEO is indicated: • For the treatment of postmenopausal women with osteoporosis at high risk for fracture (defined herein as having a history of osteoporotic fracture or multiple risk factors for fracture) or who have failed or are intolerant to other available osteoporosis therapy. In postmenopausal women with osteoporosis, FORTEO reduces the risk of vertebral and nonvertebral fractures." }, "verifiedAt": "2026-08-02" }, { "question": "Is there a generic version of teriparatide?", "answer": "Yes. Drugs@FDA lists three approved abbreviated new drug applications for teriparatide injection — ANDA 208569 (Teva Pharmaceuticals USA) and ANDA 211097 (Apotex), both approved 16 November 2023, and ANDA 213641 (Amphastar Pharmaceuticals), approved 12 December 2025 — in addition to the two new drug applications, NDA 021318 (FORTEO, Eli Lilly and Company) and NDA 211939 (BONSITY, Alvogen). Drugs@FDA records a product under each of the five with marketing status Prescription. The abbreviated pathway is the generic pathway, so teriparatide is one of the few peptides discussed in this category that has approved generics at all. What that does not tell you: Drugs@FDA is an application-level record, so it is not a statement about price, about what a given pharmacy stocks, or about substitution rules, none of which this record addresses.", "source": { "url": "https://api.fda.gov/drug/drugsfda.json?search=openfda.generic_name:%22teriparatide%22&limit=20", "title": "Drugs@FDA — applications with teriparatide as an active ingredient (openFDA drug/drugsfda)", "publisher": "FDA", "date": "2026-07-31" }, "verifiedAt": "2026-08-02" }, { "question": "Does teriparatide cause osteosarcoma in humans?", "answer": "The FDA-approved label does not say it does, and does not say it does not. Section 5.1 holds all three findings in one paragraph: an increase in the incidence of osteosarcoma, a malignant bone tumor, was observed in male and female rats treated with teriparatide; osteosarcoma has been reported in patients treated with FORTEO in the post-marketing setting; and an increased risk of osteosarcoma has not been observed in observational studies in humans. Section 6.3 reports the human data behind that third clause — two U.S. claims-based osteosarcoma surveillance studies identified three and zero cases among 379,283 and 153,316 FORTEO users respectively, results the label says 'suggest a similar risk for osteosarcoma between FORTEO users and their comparators'. The label attaches its own caution to them: interpretation 'calls for caution owing to the limitations of the data sources which do not allow for complete measurement and control for confounders'. The label also states there are limited data assessing the risk of osteosarcoma beyond 2 years of use, and it still directs that teriparatide be avoided in patients at increased baseline risk of osteosarcoma, including those with open epiphyses, Paget's disease of the bone, bone metastases or a history of skeletal malignancies, prior skeletal radiation, and hereditary predisposition. Those human surveillance findings are why the boxed warning came off in 2020 — not a finding that the risk was never real.", "source": { "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/021318s057lbl.pdf", "title": "FORTEO (teriparatide injection) — Full Prescribing Information", "publisher": "FDA", "date": "2024-07-26", "quote": "Osteosarcoma has been reported in patients treated with FORTEO in the post marketing setting; however, an increased risk of osteosarcoma has not been observed in observational studies in humans. There are limited data assessing the risk of osteosarcoma beyond 2 years of FORTEO use" }, "verifiedAt": "2026-08-02" }, { "question": "Is teriparatide on FDA's 503A compounding list?", "answer": "No — teriparatide appears in none of the three categories of FDA's list of bulk drug substances nominated for use in compounding under section 503A, in the version updated 14 May 2026. That was confirmed by fetching the document and searching the extracted text: zero hits for 'teriparatide', zero for 'parathyroid', zero for 'PTH'. Read the absence correctly, because it means something different here than it does for the research-chemical peptides. That list is a nomination track for substances that lack an approved product; teriparatide is the active ingredient in five approved applications, so it was never a candidate for it. Absence is not a category, not a safety finding, and not permission. This record therefore records no 503A compounding status for teriparatide at all, rather than labelling it 'never nominated', which would imply a proceeding it was never part of. Whether a pharmacy may lawfully compound a teriparatide preparation is a separate question turning on other parts of section 503A, and no document read for this record answers it.", "source": { "url": "https://www.fda.gov/media/94155/download", "title": "Bulk Drug Substances Nominated for Use in Compounding Under Section 503A of the Federal Food, Drug, and Cosmetic Act", "publisher": "FDA", "date": "2026-05-14" }, "verifiedAt": "2026-08-02" }, { "question": "Is teriparatide the same thing as PTH(1-34) sold as a research peptide?", "answer": "Not established, and the label is the reason to be careful rather than the reason to be confident. Teriparatide is a recombinant human parathyroid hormone analog, PTH 1-34; the FORTEO label states it has 'an identical sequence to the 34 N-terminal amino acids (the biologically active region) of the 84-amino acid human parathyroid hormone' and is manufactured using a strain of Escherichia coli modified by recombinant DNA technology. So the sequence named on a research vial and the sequence in the approved product are the same sequence. That is where the equivalence stops: a sequence name is not an identity test, and nothing in the documents behind this record establishes the contents, purity, or salt form of any unapproved material. Salt form is not a technicality here — the approved FORTEO product contains teriparatide as a free base, while Drugs@FDA lists a separate discontinued application, PARATHAR (NDA 019498), whose active ingredient it records as teriparatide acetate. The approval, the label and the fracture trial behind the approved product describe that product. They do not describe a vial.", "source": { "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/021318s057lbl.pdf", "title": "FORTEO (teriparatide injection) — Full Prescribing Information", "publisher": "FDA", "date": "2024-07-26", "quote": "FORTEO (teriparatide injection) is a recombinant human parathyroid hormone analog (PTH 1-34). It has an identical sequence to the 34 N-terminal amino acids (the biologically active region) of the 84-amino acid human parathyroid hormone." }, "verifiedAt": "2026-08-02" } ] }, { "slug": "tesamorelin", "name": "Tesamorelin", "aliases": [ "Tesamorelin acetate", "TH9507", "EGRIFTA", "EGRIFTA SV", "EGRIFTA WR", "trans-3-hexenoyl-GHRH(1-44) amide" ], "url": "https://peptides101.com/compounds/tesamorelin", "moleculeNote": "A synthetic analog of human growth hormone-releasing factor, GHRH(1-44), stabilised by a trans-3-hexenoyl group on the N-terminus. The label's own term is 'growth hormone-releasing factor (GHRF) analog'. It is a secretagogue: it does not supply growth hormone, it induces release of endogenous GH. That mechanism is why the label's malignancy contraindication and IGF-1 monitoring requirement exist, and it is the same mechanism sold casually as 'GH support'.", "quickAnswer": "Tesamorelin is an FDA-approved prescription drug — EGRIFTA, application 022505, approved 2010-11-10 — but its approval covers exactly one use: the reduction of excess abdominal fat in HIV-infected adult patients with lipodystrophy. The EGRIFTA SV label's own Limitations of Use state that it 'is not indicated for weight loss management as it has a weight neutral effect', so 'tesamorelin is FDA-approved' is true of the drug and says nothing about the fat-loss and body-recomposition uses it is sold for.", "fdaStatus": { "value": "approved", "note": "FDA-approved. Approval is always for a specific indication and population — see the approval record below, because it is routinely not the use this is marketed for.", "source": { "url": "https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=022505", "title": "Drugs@FDA: EGRIFTA (tesamorelin acetate), BLA 022505, Theratechnologies", "publisher": "FDA", "date": "2010-11-10" }, "verifiedAt": "2026-07-16" }, "compoundingStatus": null, "evidence": { "tier": "proven-in-humans", "humanAdministrationChecked": true, "note": "Administration confirmed, not inferred. The pivotal trial was opened and read: the drug was administered subcutaneously to randomised human subjects against placebo. This is the opposite of the MOTS-c and TB-500 pattern, where every apparent 'human trial' measures the endogenous peptide as a biomarker and none administers anything. The quote above is truncated: the source sentence specifies a complete regimen, and this site publishes no dosing. The truncation removes amount, frequency and duration and keeps the randomisation fact the tier rests on. THE TIER IS SCOPED TO THE APPROVED INDICATION AND NOTHING ELSE. What is proven, per the attached source: in a 2007 multicentre double-blind placebo-controlled phase 3 trial of 412 HIV-infected adults with excess abdominal fat, researchers reported visceral adipose tissue decreased 15.2% versus a 5.0% increase on placebo, and IGF-I rose 81.0% versus a 5.0% decrease on placebo. Limitations. The investigators of the second phase 3 trial (Falutz et al., J Acquir Immune Defic Syndr 2010;53(3):311-22, PMID 20101189, n=404) rerandomised patients from tesamorelin to placebo and reported, in their words, that 'the initial improvements over 6 months in VAT were rapidly lost in those switching from tesamorelin to placebo' — so any benefit those trials measured was contingent on continued use. The label separately states long-term cardiovascular safety has not been established. The studied population is HIV-infected adults on antiretroviral therapy, not healthy adults. In HIV-negative people the evidence is real but far thinner and does NOT reach this tier: a 2012 randomised, double-blind, placebo-controlled trial of 60 abdominally obese adults with reduced GH secretion (Makimura et al., J Clin Endocrinol Metab 2012;97(12):4769-79, PMID 23015655) reported a visceral fat treatment effect over 12 months with no significant effect on subcutaneous adipose tissue. One 60-subject trial in a GH-deficient-selected population is not an approval-grade evidence base for the general body-composition market, and its own finding — visceral fat moved, subcutaneous fat did not — is a poor match for what buyers are told to expect. The two studies named in this note are cited inline with journal, volume, pages and PMID because the schema attaches exactly one source per field and that slot holds the pivotal trial. Each was opened and verified individually on 2026-07-16; neither claim rides on the attached NEJM source. The pooled phase 3 analysis an earlier draft cited (n=806, JCEM 2010) has been dropped rather than left uncited — it was corroborative, not load-bearing.", "source": { "url": "https://pubmed.ncbi.nlm.nih.gov/18057338/", "title": "Metabolic effects of a growth hormone-releasing factor in patients with HIV", "publisher": "PubMed (N Engl J Med 2007;357:2359-2370)", "date": "2007-12-06", "quote": "We randomly assigned 412 patients with HIV (86% of whom were men) who had an accumulation of abdominal fat to receive … tesamorelin or placebo …" }, "verifiedAt": "2026-07-16" }, "fdaApproval": { "applicationNumber": "BLA022505", "brandName": "EGRIFTA SV", "approvedIndication": "Reduction of excess abdominal fat in HIV-infected adult patients with lipodystrophy.", "discontinued": false, "source": { "url": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=3d783378-b02d-4f19-99dd-0fc91a042224", "title": "EGRIFTA SV (tesamorelin for injection) — Highlights of Prescribing Information", "publisher": "DailyMed (FDA Structured Product Labeling)", "date": "2025-12-23", "quote": "EGRIFTA SV is indicated for the reduction of excess abdominal fat in HIV-infected adult patients with lipodystrophy." }, "verifiedAt": "2026-07-16" }, "fdaFindings": [ { "finding": "FDA-approved indication, verbatim: 'EGRIFTA SV is indicated for the reduction of excess abdominal fat in HIV-infected adult patients with lipodystrophy.'", "note": "Recorded verbatim because the gap between this sentence and the sales pitch IS the story. The indication is bounded four ways at once — a specific compartment (excess abdominal fat), a specific population (HIV-infected), a specific age group (adult), and a specific condition (lipodystrophy). Every one of those bounds is dropped when the molecule is sold for body recomposition. 'FDA-approved' is true of the drug and says nothing about that use.", "source": { "url": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=3d783378-b02d-4f19-99dd-0fc91a042224", "title": "EGRIFTA SV (tesamorelin for injection) — Highlights of Prescribing Information", "publisher": "DailyMed (FDA Structured Product Labeling)", "date": "2025-12-23", "quote": "EGRIFTA SV is indicated for the reduction of excess abdominal fat in HIV-infected adult patients with lipodystrophy." }, "verifiedAt": "2026-07-16" }, { "finding": "The label's own Limitations of Use state that EGRIFTA SV is not indicated for weight loss management as it has a weight neutral effect, and that long-term cardiovascular safety has not been established.", "note": "This is the most load-bearing sentence on the page and it is printed in section 1 of the sponsor's own label. The fat-loss market's central claim about tesamorelin is contradicted by the labeling of the product that makes the claim possible. 'Weight neutral' is not editorial hedging — it is the approved finding. The trials reported a reduction in visceral adipose tissue in a diseased population; the label states the drug is not indicated for weight loss management, and the sponsor is not permitted to say otherwise.", "source": { "url": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=3d783378-b02d-4f19-99dd-0fc91a042224", "title": "EGRIFTA SV (tesamorelin for injection) — Highlights of Prescribing Information", "publisher": "DailyMed (FDA Structured Product Labeling)", "date": "2025-12-23", "quote": "EGRIFTA SV is not indicated for weight loss management as it has a weight neutral effect." }, "verifiedAt": "2026-07-16" }, { "finding": "EGRIFTA SV is contraindicated in patients with active malignancy, in patients with disruption of the hypothalamic-pituitary axis, in known hypersensitivity to tesamorelin or excipients, and in pregnancy.", "note": "Four absolute contraindications on an approved product. The malignancy contraindication is mechanistic, not incidental: the label's stated reason is that the drug induces release of endogenous GH, a known growth factor. Section 5.1 additionally directs prescribers to weigh the increased background risk of malignancies in HIV-positive patients before starting. None of this survives a purchase that involves no prescriber and no screening.", "source": { "url": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=3d783378-b02d-4f19-99dd-0fc91a042224", "title": "EGRIFTA SV (tesamorelin for injection) — Highlights of Prescribing Information", "publisher": "DailyMed (FDA Structured Product Labeling)", "date": "2025-12-23", "quote": "EGRIFTA SV induces the release of endogenous growth hormone (GH), a known growth factor. Do not treat patients with active malignancy with EGRIFTA SV" }, "verifiedAt": "2026-07-16" }, { "finding": "Life-time carcinogenicity studies in rodents have not been conducted with tesamorelin acetate, per section 13.1 of the EGRIFTA SV label.", "note": "Read this next to the malignancy contraindication above, because the two are the same fact seen from both ends. FDA contraindicates the drug in active malignancy on the stated mechanistic ground that it induces release of endogenous GH, a known growth factor — and the standard nonclinical study that would characterise lifetime tumour risk was never run. The label does report that a battery of mutagenicity tests, including the Ames test, revealed no potential mutagenicity; mutagenicity and carcinogenicity are not the same endpoint and the label does not offer the former as an answer to the latter. This is an approved drug — the most-studied molecule in this library — and its lifetime cancer risk is an open question on its own label. Nothing about an unapproved vial of the same molecule closes that question; it only removes the prescriber who would weigh it.", "source": { "url": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=3d783378-b02d-4f19-99dd-0fc91a042224", "title": "EGRIFTA SV (tesamorelin for injection) — Highlights of Prescribing Information", "publisher": "DailyMed (FDA Structured Product Labeling)", "date": "2025-12-23", "quote": "Life-time carcinogenicity studies in rodents have not been conducted with tesamorelin acetate." }, "verifiedAt": "2026-07-16" }, { "finding": "EGRIFTA SV is not indicated for use in pediatric patients with open or closed epiphyses, and the label states that in pediatric patients with open epiphyses treatment may result in linear growth acceleration and excessive growth.", "note": "Recorded because the approved indication is bounded to ADULTS and this is the label saying why, rather than us inferring it. Section 8.4 also states plainly that safety and effectiveness in pediatric patients have not been established. Note the exclusion covers closed epiphyses too — it is not merely a growth-plate caveat that expires at skeletal maturity. The under-25 market for GH secretagogues is real, and this is the sponsor's own approved labelling refusing that population in both directions.", "source": { "url": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=3d783378-b02d-4f19-99dd-0fc91a042224", "title": "EGRIFTA SV (tesamorelin for injection) — Highlights of Prescribing Information", "publisher": "DailyMed (FDA Structured Product Labeling)", "date": "2025-12-23", "quote": "In pediatric patients with open epiphyses, treatment with EGRIFTA SV may result in linear growth acceleration and excessive growth. EGRIFTA SV is not indicated for use in pediatric patients with open or closed epiphyses." }, "verifiedAt": "2026-07-16" }, { "finding": "The label's Limitations of Use state there are no data to support improved compliance with anti-retroviral therapies in HIV-positive patients taking EGRIFTA SV.", "note": "A small sentence that does disproportionate work, and the reason it is here is scope. This is FDA declining to let the sponsor claim a downstream benefit even INSIDE the approved population, for the approved use, on the approved label. The approval buys the sponsor one claim — visceral fat reduction in HIV-infected adults with lipodystrophy — and an explicit 'no data' on the adjacent claim a reasonable person would assume followed from it. Measure the distance between that and what is claimed for an unapproved vial.", "source": { "url": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=3d783378-b02d-4f19-99dd-0fc91a042224", "title": "EGRIFTA SV (tesamorelin for injection) — Highlights of Prescribing Information", "publisher": "DailyMed (FDA Structured Product Labeling)", "date": "2025-12-23", "quote": "There are no data to support improved compliance with anti-retroviral therapies in HIV-positive patients taking EGRIFTA SV." }, "verifiedAt": "2026-07-16" } ], "safetySignals": [ { "signal": "Elevated IGF-1: the label requires monitoring IGF-1 during therapy and states that the effects of prolonged elevations in IGF-1 levels are unknown.", "note": "Elevated IGF-1 is the intended pharmacology — a GHRH analog works by inducing endogenous GH release, and IGF-1 rises downstream. The pivotal trial's own IGF-I figures are recorded under evidence above, where the trial is the attached source; they are not repeated here, because this label does not state them. It is also the reason for a labeled monitoring requirement with a discontinuation trigger. A monitoring requirement is a safety control that only exists inside a prescribing relationship; it does not travel with the molecule.", "source": { "url": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=3d783378-b02d-4f19-99dd-0fc91a042224", "title": "EGRIFTA SV (tesamorelin for injection) — Highlights of Prescribing Information", "publisher": "DailyMed (FDA Structured Product Labeling)", "date": "2025-12-23", "quote": "The effects of prolonged elevations in IGF-1 levels are unknown. Monitor IGF-1 levels during EGRIFTA SV therapy. Consider discontinuing in patients with persistent elevations." }, "verifiedAt": "2026-07-16" }, { "signal": "Glucose intolerance or diabetes mellitus may develop with use; the label directs evaluating glucose prior to and during therapy.", "note": "Worth stating precisely in both directions, because the trials cut against the intuition here. The 2012 HIV-negative trial cited under evidence above (Makimura et al., J Clin Endocrinol Metab 2012;97(12):4769-79, PMID 23015655) reported 'no changes in fasting, 2-h glucose, or glycated hemoglobin' — that finding is the trial's, not this label's. FDA nonetheless carries this as a labeled warning with a monitoring instruction. Trial-level reassurance over 26 to 52 weeks in selected populations is not the same as an absence of risk, which is precisely why the warning survived approval.", "source": { "url": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=3d783378-b02d-4f19-99dd-0fc91a042224", "title": "EGRIFTA SV (tesamorelin for injection) — Highlights of Prescribing Information", "publisher": "DailyMed (FDA Structured Product Labeling)", "date": "2025-12-23" }, "verifiedAt": "2026-07-16" }, { "signal": "Increased risk of neoplasms; fluid retention including edema, arthralgia and carpal tunnel syndrome; hypersensitivity reactions; injection site reactions; and increased mortality in patients with acute critical illness.", "note": "The label's Warnings and Precautions in full. Most commonly reported adverse reactions (>5%): arthralgia, injection site erythema, injection site pruritus, pain in extremity, peripheral edema, and myalgia. Safety was characterised in 740 HIV-infected patients with lipodystrophy, 543 of whom received drug during the 26-week placebo-controlled phase. Note the scope: this safety database is HIV-infected adults with lipodystrophy under trial monitoring. It is the best-characterised safety profile of any compound in this library and it still does not describe healthy adults using the drug for body composition, because nobody has studied that.", "source": { "url": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=3d783378-b02d-4f19-99dd-0fc91a042224", "title": "EGRIFTA SV (tesamorelin for injection) — Highlights of Prescribing Information", "publisher": "DailyMed (FDA Structured Product Labeling)", "date": "2025-12-23" }, "verifiedAt": "2026-07-16" }, { "signal": "The 2 mg/vial EGRIFTA SV formulation was not itself tested for safety; its safety is bridged from clinical trials conducted with the original 1 mg/vial EGRIFTA formulation.", "note": "A precision point that cuts against over-reading the approval, and it comes from the label rather than from us. The currently marketed product's safety is inferred from the original formulation via bridging, not established de novo. If the marketed product's own safety is a bridge from a different formulation of the same approved drug, the inferential distance from that trial evidence to an unapproved research-chemical vial of 'tesamorelin' is not a bridge at all.", "source": { "url": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=3d783378-b02d-4f19-99dd-0fc91a042224", "title": "EGRIFTA SV (tesamorelin for injection) — Highlights of Prescribing Information", "publisher": "DailyMed (FDA Structured Product Labeling)", "date": "2025-12-23", "quote": "The safety of EGRIFTA SV (2 mg/vial formulation) has been established based on clinical trials conducted with EGRIFTA (1 mg/vial formulation)." }, "verifiedAt": "2026-07-16" }, { "signal": "The 11.6 mg/vial EGRIFTA WR formulation was likewise not itself tested for safety; its safety is bridged from clinical trials conducted with the original 1 mg/vial EGRIFTA formulation.", "note": "Recorded as a separate entry with its own source because this sentence lives in the EGRIFTA WR label, not the SV one — the SV SPL contains no occurrence of 'EGRIFTA WR' or '11.6 mg'. Both SPLs carry id extension 'BLA022505', so all three formulations do sit under the same application; that is the claim the two labels jointly support. Every currently marketed strength of this drug therefore rests on trials of a formulation none of them is.", "source": { "url": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=839334d3-8c1d-4c26-9036-2ab524a6ea75", "title": "EGRIFTA WR (tesamorelin for injection) — Highlights of Prescribing Information", "publisher": "DailyMed (FDA Structured Product Labeling)", "date": "2025-03-31", "quote": "The safety of EGRIFTA WR (11.6 mg/vial formulation) has been established based on clinical trials conducted with EGRIFTA (1 mg/vial formulation)." }, "verifiedAt": "2026-07-16" }, { "signal": "Anti-tesamorelin IgG antibodies were detected in 50% of patients who received EGRIFTA for 26 weeks and 47% at 52 weeks; cross-reactivity to endogenous growth hormone-releasing hormone was observed in approximately 60% of patients who developed those antibodies.", "note": "The most under-reported fact about this molecule, and it is on the label. Roughly half of treated patients raised antibodies to the drug, and in about 60% of those the antibodies also recognised the patient's OWN GHRH. Section 12.6 further reports that neutralizing antibodies to tesamorelin and to human GHRH were detected in vitro at Week 52 in 10% and 5% of EGRIFTA-treated patients respectively, and that among a group antibody-positive at 26 weeks who were reassessed six months after stopping, 18% remained antibody positive. State the limits honestly in both directions, because the label does: patients with and without antibodies had similar mean reductions in visceral adipose tissue and similar IGF-1 response, so no loss of the measured effect was demonstrated, and the label's own preamble warns that anti-drug antibody incidence is assay-dependent and not comparable across studies. What is recorded here is exposure, not proven harm. It is recorded because an immune response against an endogenous hypothalamic hormone is the kind of thing a buyer of a 'GH support' vial has never been told is on the table.", "source": { "url": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=3d783378-b02d-4f19-99dd-0fc91a042224", "title": "EGRIFTA SV (tesamorelin for injection) — Highlights of Prescribing Information", "publisher": "DailyMed (FDA Structured Product Labeling)", "date": "2025-12-23", "quote": "Cross-reactivity to endogenous growth hormone-releasing hormone (GHRH) was observed in approximately 60% of patients who developed anti-tesamorelin antibodies." }, "verifiedAt": "2026-07-16" }, { "signal": "Tesamorelin appears in none of the three 503A categories in the FDA bulks list updated 2026-05-14.", "note": "Verified by fetching and text-extracting the document directly: zero hits. Recorded here as an anti-signal, because for this compound absence from the list means the reverse of what it means for BPC-157 or TB-500. Those are absent because their nominations were withdrawn and they remain non-compoundable. Tesamorelin is absent because an approved drug's component never enters that pathway. Do not read either absence as legality, and do not read this one as evidence that FDA reviewed and cleared tesamorelin for compounding — FDA never took up that question, because 503A never posed it.", "source": { "url": "https://www.fda.gov/media/94155/download", "title": "Bulk Drug Substances Nominated for Use in Compounding Under Section 503A of the Federal Food, Drug, and Cosmetic Act", "publisher": "FDA", "date": "2026-05-14" }, "verifiedAt": "2026-07-16" } ], "faqs": [ { "question": "Is tesamorelin FDA-approved?", "answer": "Yes, but for one indication only. FDA approved tesamorelin on 2010-11-10 under application 022505 (sponsor Theratechnologies, brand name EGRIFTA), and the approved indication is the reduction of excess abdominal fat in HIV-infected adult patients with lipodystrophy. That is the whole of the approval: it does not cover weight loss, body composition, anti-aging, athletic performance, or use in people without HIV-associated lipodystrophy, and it does not cover pediatric patients.", "source": { "url": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=3d783378-b02d-4f19-99dd-0fc91a042224", "title": "EGRIFTA SV (tesamorelin for injection) — Highlights of Prescribing Information", "publisher": "DailyMed (FDA Structured Product Labeling)", "date": "2025-12-23", "quote": "EGRIFTA SV is indicated for the reduction of excess abdominal fat in HIV-infected adult patients with lipodystrophy." }, "verifiedAt": "2026-07-16" }, { "question": "Does tesamorelin cause weight loss?", "answer": "No — the FDA-approved labeling for tesamorelin says the opposite. The EGRIFTA SV label's Limitations of Use state verbatim: 'EGRIFTA SV is not indicated for weight loss management as it has a weight neutral effect.' What the pivotal trials measured was a reduction in visceral adipose tissue in HIV-infected adults with lipodystrophy, which is not the same endpoint as body weight; the label states the drug is weight neutral. The sponsor is not permitted to market tesamorelin for weight loss, and the reason is printed in section 1 of its own label.", "source": { "url": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=3d783378-b02d-4f19-99dd-0fc91a042224", "title": "EGRIFTA SV (tesamorelin for injection) — Highlights of Prescribing Information", "publisher": "DailyMed (FDA Structured Product Labeling)", "date": "2025-12-23", "quote": "EGRIFTA SV is not indicated for weight loss management as it has a weight neutral effect." }, "verifiedAt": "2026-07-16" }, { "question": "Is there any human evidence that tesamorelin works?", "answer": "Yes — tesamorelin has more human evidence behind it than any other compound in this library, and that evidence is scoped to HIV-associated lipodystrophy. In a 2007 multicentre double-blind placebo-controlled phase 3 trial of 412 HIV-infected adults with excess abdominal fat (Falutz et al., N Engl J Med 2007;357:2359-2370), researchers reported visceral adipose tissue decreased 15.2% on tesamorelin versus a 5.0% increase on placebo. Two limits matter. The investigators of the second phase 3 trial (J Acquir Immune Defic Syndr 2010;53(3):311-22, n=404) rerandomised patients from tesamorelin to placebo and reported the initial improvements in visceral fat were rapidly lost, so the benefit was contingent on continued use. And in HIV-negative people the evidence is far thinner: the largest such trial (Makimura et al., J Clin Endocrinol Metab 2012;97(12):4769-79) randomised 60 abdominally obese adults with reduced growth hormone secretion and reported a visceral fat effect with no significant effect on subcutaneous fat.", "source": { "url": "https://pubmed.ncbi.nlm.nih.gov/18057338/", "title": "Metabolic effects of a growth hormone-releasing factor in patients with HIV", "publisher": "PubMed (N Engl J Med 2007;357:2359-2370)", "date": "2007-12-06", "quote": "We randomly assigned 412 patients with HIV (86% of whom were men) who had an accumulation of abdominal fat to receive … tesamorelin or placebo …" }, "verifiedAt": "2026-07-16" }, { "question": "Can I get tesamorelin from a compounding pharmacy?", "answer": "Tesamorelin is not blocked by FDA's 503A bulks list — but that is not the permission it is often taken for, and a different provision of the same statute is the one that bites. Under 21 U.S.C. 353a(b)(1)(A)(i), the bulks list is only reached for a substance that has no USP/NF monograph AND is not a component of an FDA-approved drug; tesamorelin is a component of an approved drug (EGRIFTA), so it never enters that pathway and its absence from the list reflects nothing FDA decided about it. Separately, 353a(b)(1)(D) bars compounding, regularly or in inordinate amounts, any drug product that is essentially a copy of a commercially available drug product — and both EGRIFTA products are listed in Drugs@FDA with marketing status 'Prescription' as of 2026-07-16. That bar has a statutory exception, and any honest answer has to state it: 353a(b)(2) provides that 'essentially a copy of a commercially available drug product' does not include a drug product in which there is a change, made for an identified individual patient, which produces for that patient a significant difference, as determined by the prescribing practitioner. That is the provision compounded versions of approved drugs run through, and whether any given preparation qualifies is a determination for the prescriber, not something this page can answer. What does not turn on it: section 353a(a) conditions the entire exemption on a drug compounded for an identified individual patient based on a valid prescription order, so nothing in 503A reaches a vial bought online without one.", "source": { "url": "https://uscode.house.gov/view.xhtml?req=granuleid:USC-prelim-title21-section353a&num=0&edition=prelim", "title": "21 U.S.C. 353a — Pharmacy compounding (FD&C Act section 503A)", "publisher": "Office of the Law Revision Counsel, U.S. House of Representatives", "date": "2025-01-06", "quote": "does not compound regularly or in inordinate amounts (as defined by the Secretary) any drug products that are essentially copies of a commercially available drug product. … For purposes of paragraph (1)(D), the term \"essentially a copy of a commercially available drug product\" does not include a drug product in which there is a change, made for an identified individual patient, which produces for that patient a significant difference, as determined by the prescribing practitioner, between the compounded drug and the comparable commercially available drug product." }, "verifiedAt": "2026-07-16" }, { "question": "Is tesamorelin safe?", "answer": "Tesamorelin has the best-characterised safety profile of any compound in this library, and that profile is not a clean bill of health. Its FDA-approved labeling carries four absolute contraindications — active malignancy, disruption of the hypothalamic-pituitary axis, known hypersensitivity, and pregnancy — with the malignancy contraindication resting on the label's stated ground that the drug induces release of endogenous growth hormone, a known growth factor. The label additionally states that life-time carcinogenicity studies in rodents have not been conducted with tesamorelin acetate, that the effects of prolonged elevations in IGF-1 are unknown and IGF-1 must be monitored during therapy, and that long-term cardiovascular safety has not been established. Every one of those is a control that exists inside a prescribing relationship; none of them travels with the molecule. The safety database is also scoped to 740 HIV-infected adults with lipodystrophy under trial monitoring — nobody has studied healthy adults using tesamorelin for body composition.", "source": { "url": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=3d783378-b02d-4f19-99dd-0fc91a042224", "title": "EGRIFTA SV (tesamorelin for injection) — Highlights of Prescribing Information", "publisher": "DailyMed (FDA Structured Product Labeling)", "date": "2025-12-23", "quote": "Life-time carcinogenicity studies in rodents have not been conducted with tesamorelin acetate." }, "verifiedAt": "2026-07-16" } ] }, { "slug": "thymalin", "name": "Thymalin", "aliases": [ "Timalin", "Тималин", "thymus polypeptide complex" ], "url": "https://peptides101.com/compounds/thymalin", "moleculeNote": "Thymalin is not a defined synthetic peptide. The 2021 trial describes it as 'a complex of peptides isolated from the thymus of calves with a molecular weight of up to 10 kDa' — an animal-tissue extract, manufactured by Samson-Med LLC (St. Petersburg) and identified in that paper by a drug series number. Three separate substances are routinely collapsed into this name and should not be: (i) thymalin, the calf-thymus extract; (ii) the Lys-Glu (KE) and Glu-Trp (EW) dipeptides described in a 2023 paper as active substances of thymalin and sold separately; and (iii) thymosin alpha-1 (thymalfasin), a defined 28-amino-acid peptide with its own record on this site. FDA has ruled on exactly this extract-versus-analogue question for the pineal pair from the same Russian research programme, holding that epithalamin (the gland extract) and epitalon (the synthetic tetrapeptide) 'are different substances' — so a study of the extract is not evidence about the analogue, and the reverse also holds.", "quickAnswer": "Thymalin, a polypeptide extract of calf thymus, is not an FDA-approved drug: FDA named a 'Thymalin' product as an unapproved new drug and a misbranded drug in a February 2024 warning letter, stating that no application under section 505 of the Federal Food, Drug, and Cosmetic Act is in effect for it, and thymalin appears in no category of FDA's 503A bulk drug substances list. Thymalin has genuinely been administered to humans — in a 2021 single-centre, open-label, randomised controlled trial, 42 hospitalised COVID-19 patients received it intramuscularly alongside standard care — but that trial reported laboratory markers only, with no clinical outcomes and no adverse-event data.", "fdaStatus": { "value": "not-approved", "note": "Sourced to an FDA document that names thymalin, rather than to an absence. Drugs@FDA was queried four ways on 2026-08-02 via the openFDA API — openfda.generic_name, openfda.brand_name, openfda.substance_name and products.active_ingredients.name — and all four returned NOT_FOUND, with a semaglutide control query on the same field returning six applications, so the empty result is a fact about the database and not an artifact of the query. That is still only an absence, which is why the sourced quote is FDA's own affirmative statement that no section 505 application is in effect. NOT 'investigational', and the distinction is the one this vocabulary exists to hold: a ClinicalTrials.gov API query for 'thymalin' on 2026-08-02 returned an empty study list — not one registration, anywhere, by anyone. There is no identifiable sponsor pursuing US approval, so there is no development programme to be in. Separately, and this is where readers get misled in the other direction: the 2021 trial authors state that thymalin 'has been approved by the Ministry of Health of the Russian Federation for medical use since 1982' and give a manufacturer and a registration certificate number. We did NOT independently verify that against the Russian State Register of Medicines, and we record it as the authors' statement rather than as a verified fact. Even if it is exactly right, a Russian registration is not an FDA status and confers nothing in the United States.", "source": { "url": "https://www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/warning-letters/us-chem-labs-669074-02072024", "title": "US Chem Labs — Warning Letter, MARCS-CMS 669074", "publisher": "FDA", "date": "2024-02-07", "quote": "No approved applications pursuant to section 505 of the FD&C Act, 21 U.S.C. 355 are in effect for these products." }, "verifiedAt": "2026-08-02" }, "compoundingStatus": null, "evidence": { "tier": "promising-but-unproven", "humanAdministrationChecked": true, "note": "Administration check RUN AND PASSED on the full text, not on an abstract. In Khavinson et al. 2021 thymalin was given intramuscularly to 42 hospitalised COVID-19 patients against 50 standard-care controls; the paper is open access in PubMed Central and states its own design in the sentence quoted above. The endogenous-biomarker trap that reduces MOTS-c's apparent four human RCTs to zero cannot apply to thymalin at all: it is a manufactured calf-thymus extract with a named manufacturer and a lot number, and there is no endogenous 'thymalin' in a person to measure by mistake. WHY THIS IS NOT 'PROVEN', and the list is long. The 2021 trial was open-label with no placebo, single-centre, and reported ONLY laboratory endpoints — IL-6, C-reactive protein, D-dimer, fibrinogen, ferritin, CD3/CD4/CD8 counts and blood cell ratios. Read against a text search of the full paper, the words 'adverse', 'safety', 'tolerability', 'placebo', 'blind', 'died' and 'discharge' do not appear ANYWHERE in it. No mortality, no ventilation, no length of stay, no adverse-event table: the trial measured markers, not patients' outcomes. Co-interventions were heavy and unbalanced — hydroxychloroquine and lopinavir/ritonavir, both since abandoned for COVID-19, were given to differing proportions of the two arms — and the paper reports no trial registration and no power calculation. The senior author is at the Saint Petersburg Institute of Bioregulation and Gerontology, the institute behind thymalin's development; the paper's declaration reads 'There is no conflict of interest.' THE OTHER HUMAN STUDY, and it is the one the consumer market actually runs on: Khavinson and Morozov 2003 reports thymalin and epithalamin given to 266 elderly persons over 6-8 years with mortality reported as several-fold lower than control. PubMed indexes it as a Randomized Controlled Trial, but the ABSTRACT describes no randomisation, no blinding and no allocation method, and the full text we located is a scanned image with no extractable text — so nothing about its design was confirmed beyond the MEDLINE publication-type tag. An extraordinary mortality claim from a single research group in a low-circulation journal, whose methods we could not read, is not something this record will carry as established. BREADTH DOES NOT RESCUE IT EITHER. PubMed indexes roughly a dozen further thymalin studies tagged Clinical Trial or Randomized Controlled Trial — in tuberculosis, peritonitis, erysipelas, dysentery, ulcerative colitis, parkinsonism and schizophrenia, dating from 1982 to 2007 — and every one of them is Russian- or Ukrainian-language, none was opened for this record, and none is counted toward this tier. Counting them would be the exact error the editorial policy names. The tier rests on one trial that was read.", "source": { "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7877506/", "title": "Results and Prospects of Using Activator of Hematopoietic Stem Cell Differentiation in Complex Therapy for Patients with COVID-19 (Khavinson, Kuznik, Trofimova et al.)", "publisher": "Stem Cell Reviews and Reports (PubMed Central, PMC7877506)", "date": "2021-02-11", "quote": "The single-center, open-label, prospective, randomized, controlled trial included patients hospitalized in St. Petersburg City General Hospital No. 2 with a clinical diagnosis of U07.1, COVID-19, virus identified, during April - July 2020. […] All patients were divided into 2 groups: the main group consisted of 42 patients (25 women and 17 men) who received treatment according to the standard regimen in combination with thymalin; the control group included 50 patients (27 women and 23 men) who received treatment according to the standard regimen." }, "verifiedAt": "2026-08-02" }, "fdaApproval": null, "fdaFindings": [ { "finding": "FDA identified a 'Thymalin' product by name as an unapproved new drug, in a February 7, 2024 warning letter to US Chem Labs of Miami, Florida, alongside that seller's semaglutide and tirzepatide products.", "note": "This is the finding that distinguishes thymalin from most of the research-chemical market, where FDA's position has to be inferred from a substance's absence from a list. Here FDA wrote the sentence. Note what makes a product a 'new drug' in FDA's reasoning: not the molecule's novelty but the seller's claims — FDA states the products 'are not generally recognized as safe and effective for the above referenced uses and, therefore, are new drugs under section 201(p) of the FD&C Act.' The uses came off the website.", "source": { "url": "https://www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/warning-letters/us-chem-labs-669074-02072024", "title": "US Chem Labs — Warning Letter, MARCS-CMS 669074", "publisher": "FDA", "date": "2024-02-07", "quote": "your 'Semaglutide,' 'Tirzepatide' and 'Thymalin' products are unapproved new drugs introduced or delivered for introduction into interstate commerce in violation of sections 505(a) and 301(d) of the Federal Food, Drug, and Cosmetic Act (FD&C Act), 21 U.S.C. 355(a) and 301(d)." }, "verifiedAt": "2026-08-02" }, { "finding": "FDA rejected the 'research chemicals only' and 'not for human consumption' labelling on the thymalin product, holding that website evidence established the products were intended to be drugs for human use.", "note": "Record this as a legal theory that FAILED, because it is the theory nearly every thymalin vendor still relies on. The disclaimer did not defeat intended use; FDA read the site copy and treated the claims on it as the evidence. FDA's word in the letter is 'Despite'. A product sold with a research-use disclaimer and a page explaining what it does for the immune system is, on FDA's reading, a drug being sold without an approved application.", "source": { "url": "https://www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/warning-letters/us-chem-labs-669074-02072024", "title": "US Chem Labs — Warning Letter, MARCS-CMS 669074", "publisher": "FDA", "date": "2024-02-07", "quote": "Despite statements on your product labeling marketing your products as 'research chemicals only' and 'not for human consumption,' evidence obtained from your website establishes that your products are intended to be drugs for human use." }, "verifiedAt": "2026-08-02" }, { "finding": "FDA stated it was 'particularly concerned' that the seller marketed its thymalin product for use in children, and that the product had not been evaluated by FDA for safety, effectiveness, and quality.", "note": "FDA singled out the paediatric marketing for its own paragraph — the letter's only product-specific escalation, and it attaches to thymalin rather than to the two GLP-1 products. FDA's stated reason is that 'The use of untested drugs can have unpredictable and unintended consequences, especially in vulnerable populations such as children and infants'. FDA repeated the point in its own press summary the following week, describing the product as offered 'for both adults and children, for treatment of various conditions, such as immunosuppression after chemotherapy in cancer patients.' The paediatric indication is not an American invention: it tracks the Soviet-era label the seller reproduced.", "source": { "url": "https://www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/warning-letters/us-chem-labs-669074-02072024", "title": "US Chem Labs — Warning Letter, MARCS-CMS 669074", "publisher": "FDA", "date": "2024-02-07", "quote": "In addition, FDA is particularly concerned that you market your 'Thymalin' product for use in children. Your product has not been evaluated by FDA for safety, effectiveness, and quality." }, "verifiedAt": "2026-08-02" }, { "finding": "FDA also found the thymalin product misbranded, on the ground that its labeling fails to bear adequate directions for use and that it is a prescription drug for which such directions cannot be written for a layperson.", "note": "Two independent violations, not one, and the second is the one with teeth. Misbranding under 502(f)(1) turns on how the product was LABELLED, which means it does not depend on resolving anything about thymalin's biology, its Russian registration, or any evidence question. It is also the provision that carries criminal exposure in this market generally. Approval status and labelling exposure are separate questions with separate answers.", "source": { "url": "https://www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/warning-letters/us-chem-labs-669074-02072024", "title": "US Chem Labs — Warning Letter, MARCS-CMS 669074", "publisher": "FDA", "date": "2024-02-07", "quote": "Your 'Semaglutide,' 'Tirzepatide' and 'Thymalin' products are also misbranded under section 502(f)(1) of the FD&C Act, 21 U.S.C. 352(f)(1), in that their labeling fails to bear adequate directions for their intended use(s)." }, "verifiedAt": "2026-08-02" }, { "finding": "Thymalin appears in none of the three categories of FDA's 503A bulks list updated May 14, 2026, and does not appear in FDA's table of bulk drug substances 'nominated but withdrawn' — the table that carries AOD-9604, BPC-157, cathelicidin LL-37, CJC-1295, dihexa acetate, emideltide, epitalon, GHK-Cu and ipamorelin acetate.", "note": "Both documents were fetched with a browser user-agent and text-extracted locally on 2026-08-02; 'thymalin' returns zero hits in each. Be precise about what that does and does not establish. It establishes ABSENCE — thymalin is in no category and on no list. It does NOT establish that thymalin was never nominated, which is why this record carries no 503A compounding status at all rather than asserting one. The operative consequence for a reader stands on the absence alone and needs nothing further: a bulk drug substance that is neither the subject of a USP monograph nor a component of an approved drug must appear on the 503A bulks list to be used in 503A compounding, and thymalin does not appear on it.", "source": { "url": "https://www.fda.gov/media/94155/download", "title": "Bulk Drug Substances Nominated for Use in Compounding Under Section 503A of the Federal Food, Drug, and Cosmetic Act", "publisher": "FDA", "date": "2026-05-14", "quote": "Visit Safety Risks Associated with Certain Bulk Drug Substances for Use in Compounding for a summary of the identified safety risks for bulk drug substances in category 2, as well as other bulk drug substances that were previously in category 2 but were withdrawn." }, "verifiedAt": "2026-08-02" }, { "finding": "Across all seven FDA briefing documents prepared for the July 23-24, 2026 Pharmacy Compounding Advisory Committee meeting, the word 'thymalin' appears exactly once — on page 61 of the epitalon document, inside the nomination material FDA reproduced, not in FDA's own analysis. FDA has published no evaluation of thymalin.", "note": "All seven briefing documents were downloaded and text-extracted on 2026-08-02: BPC-157, emideltide, KPV, MOTS-c, semax and TB-500 return zero hits for 'thymalin'; the epitalon document returns one, on page 61, which falls after the divider page headed 'Epitalon-Related Bulk Drug Substances … Nominations'. It is the nominator's narrative, not FDA's — the sentence claims a mortality rate 4.1 times lower in people given thymalin and epithalamin, and it is reproduced there as submitted material. Do not cite it as an FDA finding. What IS in FDA's own voice is the quoted sentence, and it matters twice over. First, FDA read Khavinson and Morozov 2003 — the same paper the thymalin longevity claim rests on — and set it aside as evidence about a different substance than the one under evaluation. Second, the same document records that FDA 'could not evaluate the full article by Korkorshko et al. 2007 because it was in the Russian language' and 'searched multiple databases and were unable to locate the full article in English.' That is the procedural reality for a literature that is almost entirely Russian: FDA does not read it. Thymalin has never been through a PCAC evaluation, so no FDA staff proposal on it exists either way.", "source": { "url": "https://www.fda.gov/media/193345/download", "title": "Epitalon-Related Bulk Drug Substances — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, July 23-24, 2026", "publisher": "FDA", "date": "2026-07-23", "quote": "Seven of the articles submitted (Anisimov et al. 2001a; Khavinson and Morozov 2003; Korkushko et al. 2004; Korkushko et al. 2006; Korkushko et al. 2011; Labunets et al. 2007; Slepushkin et al. 1983) discussed the use of epithalamin; however, we note that epitalon and epithalamin are different substances." }, "verifiedAt": "2026-08-02" } ], "safetySignals": [ { "signal": "FDA states the thymalin product it examined 'has not been evaluated by FDA for safety, effectiveness, and quality', and that untested drugs can have unpredictable and unintended consequences, especially in children and infants.", "note": "An information gap, stated by FDA, not a documented harm — and the two are different things that this market habitually merges in the wrong direction. Our own FAERS query through the openFDA drug/event endpoint on 2026-08-02 returned no reports for 'THYMALIN' or 'TIMALIN'. That is what we checked, not a demonstration of safety: a substance sold under a research-use label, by sellers FDA says are marketing it as a drug, is exactly the kind of exposure that does not reach FAERS at all.", "source": { "url": "https://www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/warning-letters/us-chem-labs-669074-02072024", "title": "US Chem Labs — Warning Letter, MARCS-CMS 669074", "publisher": "FDA", "date": "2024-02-07", "quote": "Your product has not been evaluated by FDA for safety, effectiveness, and quality. The use of untested drugs can have unpredictable and unintended consequences, especially in vulnerable populations such as children and infants who may be at greater risk for adverse reactions associated with certain drug products due to differences in the ability of children to absorb, metabolize, distribute, or excrete such drug products or their metabolites." }, "verifiedAt": "2026-08-02" }, { "signal": "The one randomised controlled trial of thymalin available in English full text reports no adverse-event data of any kind: the words 'adverse', 'safety' and 'tolerability' do not appear in it.", "note": "Verified by full-text search of the PMC copy on 2026-08-02, and recorded because the absence is easy to mistake for a clean result. Ninety-two hospitalised patients were followed, 42 of them given thymalin, and the paper reports laboratory markers only — no adverse events, no tolerability assessment, no deaths, and no discharge or ventilation outcomes. A trial that did not look for harm cannot report finding none. Anyone citing this trial as evidence that thymalin is well tolerated is citing a section of it that does not exist.", "source": { "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7877506/", "title": "Results and Prospects of Using Activator of Hematopoietic Stem Cell Differentiation in Complex Therapy for Patients with COVID-19 (Khavinson, Kuznik, Trofimova et al.)", "publisher": "Stem Cell Reviews and Reports (PubMed Central, PMC7877506)", "date": "2021-02-11" }, "verifiedAt": "2026-08-02" } ], "faqs": [ { "question": "Is Thymalin FDA-approved?", "answer": "No. FDA named a 'Thymalin' product as an unapproved new drug in a warning letter dated February 7, 2024 to US Chem Labs, and stated plainly that 'No approved applications pursuant to section 505 of the FD&C Act, 21 U.S.C. 355 are in effect for these products.' A search of Drugs@FDA through the openFDA API returns no match for thymalin under generic name, brand name, substance name or active ingredient. Thymalin is also not in clinical development toward US approval: ClinicalTrials.gov registers no thymalin study at all. The 2021 trial authors state the drug has been approved by the Ministry of Health of the Russian Federation since 1982, which is a Russian registration and not an FDA status.", "source": { "url": "https://www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/warning-letters/us-chem-labs-669074-02072024", "title": "US Chem Labs — Warning Letter, MARCS-CMS 669074", "publisher": "FDA", "date": "2024-02-07", "quote": "No approved applications pursuant to section 505 of the FD&C Act, 21 U.S.C. 355 are in effect for these products." }, "verifiedAt": "2026-08-02" }, { "question": "Is there any human evidence that Thymalin works?", "answer": "Yes, thymalin has been administered to humans — but the strongest study readable in English measured laboratory markers rather than whether anyone got better. In a 2021 trial its authors describe as 'single-center, open-label, prospective, randomized, controlled', 42 hospitalised COVID-19 patients in St. Petersburg received thymalin intramuscularly alongside standard therapy and 50 received standard therapy alone; the investigators reported faster decline in interleukin-6, C-reactive protein and D-dimer in the thymalin group. The trial had no placebo, no blinding, no registration, and reported no mortality, ventilation, discharge or adverse-event outcomes. Roughly a dozen further thymalin trials are indexed in PubMed from 1982 to 2007, in tuberculosis, peritonitis, ulcerative colitis and other conditions, but all are Russian- or Ukrainian-language and none was opened for this record. FDA has published no evaluation of any of them.", "source": { "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7877506/", "title": "Results and Prospects of Using Activator of Hematopoietic Stem Cell Differentiation in Complex Therapy for Patients with COVID-19 (Khavinson, Kuznik, Trofimova et al.)", "publisher": "Stem Cell Reviews and Reports (PubMed Central, PMC7877506)", "date": "2021-02-11", "quote": "The single-center, open-label, prospective, randomized, controlled trial included patients hospitalized in St. Petersburg City General Hospital No. 2 with a clinical diagnosis of U07.1, COVID-19, virus identified, during April - July 2020." }, "verifiedAt": "2026-08-02" }, { "question": "Can I legally buy Thymalin as a research chemical?", "answer": "A research-use disclaimer did not work for the one thymalin seller FDA has written to. In its February 2024 warning letter FDA held: 'Despite statements on your product labeling marketing your products as research chemicals only and not for human consumption, evidence obtained from your website establishes that your products are intended to be drugs for human use.' FDA then found the thymalin product both an unapproved new drug under sections 505(a) and 301(d) and a misbranded drug under section 502(f)(1), because its labeling fails to bear adequate directions for its intended use. The claims on the seller's own page were the evidence FDA used. Note that the misbranding finding turns on labelling rather than on any question about thymalin itself.", "source": { "url": "https://www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/warning-letters/us-chem-labs-669074-02072024", "title": "US Chem Labs — Warning Letter, MARCS-CMS 669074", "publisher": "FDA", "date": "2024-02-07", "quote": "Despite statements on your product labeling marketing your products as 'research chemicals only' and 'not for human consumption,' evidence obtained from your website establishes that your products are intended to be drugs for human use." }, "verifiedAt": "2026-08-02" }, { "question": "Was Thymalin part of the July 2026 FDA advisory committee meeting on peptides?", "answer": "No. The seven substances before the Pharmacy Compounding Advisory Committee on July 23-24, 2026 were BPC-157, emideltide (DSIP), epitalon, KPV, MOTS-c, semax and TB-500. Thymalin was not among them and has never been evaluated by that committee, so no FDA staff proposal on thymalin exists in either direction. Across all seven briefing documents the word 'thymalin' appears exactly once, on page 61 of the epitalon document, inside the nomination material FDA reproduced rather than in FDA's own analysis. Thymalin also appears in no category of FDA's 503A bulks list, so a 503A pharmacy has no lawful basis to compound from it.", "source": { "url": "https://www.fda.gov/media/193771/download", "title": "Pharmacy Compounding Advisory Committee Meeting, July 23-24, 2026 — Agenda", "publisher": "FDA", "date": "2026-07-23", "quote": "During the morning session, the committee will discuss the following bulk drug substances being considered for inclusion on the list of bulk drug substances that can be used to compound drug products in accordance with section 503A of the FD&C Act: BPC-related bulk drug substances (BPC-157 (free base) / BPC-157 acetate) and KPV-related bulk drug substances (KPV (free base) / KPV acetate)." }, "verifiedAt": "2026-08-02" }, { "question": "Is Thymalin the same thing as thymosin alpha-1?", "answer": "No. Thymalin is a polypeptide complex extracted from calf thymus, described in a 2021 trial as 'a complex of peptides isolated from the thymus of calves with a molecular weight of up to 10 kDa'. Thymosin alpha-1 (thymalfasin) is a single defined 28-amino-acid peptide with its own regulatory and evidence record. Thymalin is also distinct from the Lys-Glu and Glu-Trp dipeptides that a 2023 paper describes as its active substances and that are sold separately. FDA has drawn precisely this distinction for the equivalent pineal pair from the same Russian research programme, holding that the gland extract epithalamin and the synthetic tetrapeptide epitalon 'are different substances' — which means evidence about one is not evidence about the other.", "source": { "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7877506/", "title": "Results and Prospects of Using Activator of Hematopoietic Stem Cell Differentiation in Complex Therapy for Patients with COVID-19 (Khavinson, Kuznik, Trofimova et al.)", "publisher": "Stem Cell Reviews and Reports (PubMed Central, PMC7877506)", "date": "2021-02-11", "quote": "One of these drugs is thymalin, which is a complex of peptides isolated from the thymus of calves with a molecular weight of up to 10 kDa." }, "verifiedAt": "2026-08-02" }, { "question": "Did FDA say anything about Thymalin being sold for children?", "answer": "Yes. FDA stated in its February 2024 warning letter: 'In addition, FDA is particularly concerned that you market your Thymalin product for use in children. Your product has not been evaluated by FDA for safety, effectiveness, and quality.' FDA gave as its reason that untested drugs 'can have unpredictable and unintended consequences, especially in vulnerable populations such as children and infants', and repeated the point in its own press summary of February 13, 2024, which described the seller as offering thymalin 'for both adults and children, for treatment of various conditions, such as immunosuppression after chemotherapy in cancer patients.' This was the only product-specific escalation in a letter that also covered semaglutide and tirzepatide.", "source": { "url": "https://www.fda.gov/news-events/press-announcements/fda-roundup-february-13-2024", "title": "FDA Roundup: February 13, 2024", "publisher": "FDA", "date": "2024-02-13", "quote": "In addition, the firm offers a product called 'thymalin' (not related to semaglutide or tirzepatide) for both adults and children, for treatment of various conditions, such as immunosuppression after chemotherapy in cancer patients." }, "verifiedAt": "2026-08-02" } ] }, { "slug": "thymosin-alpha-1", "name": "Thymosin alpha-1", "aliases": [ "Thymalfasin", "Tα1", "Ta1", "Zadaxin", "Thymosin α1", "Thymosin alfa 1" ], "url": "https://peptides101.com/compounds/thymosin-alpha-1", "moleculeNote": "A synthetic 28-amino-acid peptide identical to the naturally occurring thymic peptide. FDA's withdrawn-nomination table names it 'Thymosin-alpha 1 (Ta1)'. Do not confuse it with two neighbouring substances that are easy to conflate: THYMULIN ACETATE, a different thymic peptide, which IS in Category 3 of the 503A list (nominated without adequate support); and THYMOSIN BETA-4 FRAGMENT (TB-500), an unrelated molecule with an entirely different FDA record — FDA identified no human exposure data at all for that one, a finding that emphatically does not apply here.", "quickAnswer": "Thymosin alpha-1 is not FDA-approved and cannot lawfully be compounded in the United States: FDA has approved no drug product containing it, and on December 4, 2024 FDA's Pharmacy Compounding Advisory Committee voted 17 to 4 against adding it to the 503A bulks list, after FDA concluded there was a lack of evidence of effectiveness across all twelve uses it evaluated. Unlike most peptides sold online, thymosin alpha-1 does have a real human evidence base — it has been given to humans in placebo-controlled Phase 3 trials enrolling over a thousand people — but those trials did not find a benefit on their primary endpoints, so the accurate statement is that it was properly tested and the trials came back negative, not that it is untested.", "fdaStatus": { "value": "not-approved", "note": "Not an FDA-approved drug for any indication, and not in active development toward approval. That says nothing about whether it is sold — it is.", "source": { "url": "https://www.fda.gov/drugs/human-drug-compounding/certain-bulk-drug-substances-use-compounding-may-present-significant-safety-risks", "title": "Certain Bulk Drug Substances for Use in Compounding that May Present Significant Safety Risks", "publisher": "FDA", "date": "2026-05-14", "quote": "Bulk drug substances nominated but withdrawn" }, "verifiedAt": "2026-07-16" }, "compoundingStatus": { "value": "withdrawn-from-nomination", "note": "Absent from Categories 1, 2 and 3 of the list updated 2026-05-14 — verified by fetching and text-extracting the document directly. 'Withdrawn' rather than 'never-nominated' is not an inference: FDA's Category 2 page lists 'Thymosin-alpha 1 (Ta1)' by name in its table of 'bulk drug substances previously in category 2 of the interim policies [that] were withdrawn by the nominators'. It left Category 2 because the nominators withdrew, not because FDA cleared it. It did not enter Category 1, it is not on the 503A bulks list, and it remains non-compoundable. Note the direction of travel is the opposite of the July 2026 'peptides are becoming legal again' content wave: status moved sideways, and FDA's stated safety concern was never resolved — it was mooted.", "source": { "url": "https://www.fda.gov/drugs/human-drug-compounding/certain-bulk-drug-substances-use-compounding-may-present-significant-safety-risks", "title": "Certain Bulk Drug Substances for Use in Compounding that May Present Significant Safety Risks", "publisher": "FDA", "date": "2026-05-14", "quote": "Bulk drug substances nominated but withdrawn" }, "verifiedAt": "2026-07-16" }, "evidence": { "tier": "promising-but-unproven", "humanAdministrationChecked": true, "note": "ADMINISTRATION CHECK PASSED, AND IT MATTERS THAT IT DID. Every study underpinning this tier was opened and confirmed to ADMINISTER exogenous thymosin alpha-1 to humans — subcutaneous injection versus placebo — not to measure an endogenous peptide as a biomarker. This is the distinction that reduces MOTS-c and TB-500 to zero human trials. Thymosin alpha-1 does not fail that test. Its human evidence base is genuine.\n\nTHE BOUNDARY CALL, ARGUED. 'Proven-in-humans' requires efficacy ESTABLISHED by adequate and well-controlled trials. Two Phase 3 trials meeting that description were run, and both missed. In the 2025 TESTS trial (NCT02867267, n=1106, 22 centres in China, double blinded, placebo controlled — the source cited on this field), researchers reported 28-day all-cause mortality of 23.4% with thymosin α1 versus 24.1% with placebo (HR 0.99, 95% CI 0.77-1.27, P=0.93), with no secondary or safety outcome differing statistically significantly. In a 2012 Phase 3 trial of 552 peginterferon/ribavirin non-responders with chronic hepatitis C (NCT01178996, sponsor sigma-tau — Ciancio et al., cited in full on the hepatitis C FAQ below), researchers reported sustained viral response of 12.7% versus 10.5% on intention-to-treat (P=0.407) and concluded the drug 'seems to play no role in the primary therapy of the disease'. Limitations cut both ways: that trial's significant result (41.0% vs 26.3%, P=0.048) came from a 48-week completer subgroup, not the ITT primary, and completer analyses discard the randomisation that made the trial informative.\n\nWHY THE TRIAL COUNT MISLEADS. A 2025 systematic review of thymosin α1 in sepsis (Frontiers in Cellular and Infection Microbiology, cited in full on the meta-analysis FAQ below) pooled 11 RCTs (967 patients in the thymosin α1 group, 960 in the control group) and reported a significant 28-day mortality reduction (OR 0.73, 95% CI 0.59-0.90, P=0.003) — but the same authors reported that the benefit did not survive restriction to high-quality trials (OR 0.82, 95% CI 0.65-1.03, P=0.09) or to multicentre trials (OR 0.86, 95% CI 0.68-1.08, P=0.20). A pooled effect that disappears as trial quality rises characterises the small trials, not the drug. Counting studies would have produced the wrong tier here just as surely as it does for MOTS-c — in the other direction.\n\nNON-US APPROVAL IS NOT FDA APPROVAL. Thymalfasin is marketed outside the United States, and vendors cite the foreign-approval count as though it settled the question. It does not: FDA has approved no drug product containing thymalfasin (verified 2026-07-16 against Drugs@FDA, which returns no match for thymalfasin, Zadaxin or thymosin), and the US development programme that would have produced one did not succeed. On the foreign-approval count itself, FDA did the work and reported the result: it traced the claim to SciClone Pharmaceuticals' 2014 Annual Report and recorded that it 'is unable to independently verify these claims of approval in all the specified countries' (see fdaFindings below). That is stronger than our earlier silence, and it does not change this tier either way — the tier turns on whether efficacy was established, not on how many authorities were persuaded.\n\nThe precise statement: real, repeated, well-controlled human administration; efficacy not established for any indication; two Phase 3 programmes tested and negative on their primary endpoints. This tier explicitly includes programmes that were tested and failed. That is what this is — and it is a materially stronger evidence base than any other withdrawn-from-nomination peptide in this corpus, which is exactly why the label needs the note.", "source": { "url": "https://pubmed.ncbi.nlm.nih.gov/39814420/", "title": "The efficacy and safety of thymosin α1 for sepsis (TESTS): multicentre, double blinded, randomised, placebo controlled, phase 3 trial", "publisher": "BMJ", "date": "2025-01-15", "quote": "This trial found no clear evidence to suggest that thymosin α1 decreases 28 day all cause mortality in adults with sepsis." }, "verifiedAt": "2026-07-16" }, "fdaApproval": null, "fdaFindings": [ { "finding": "FDA identified potential significant safety risks for thymosin alpha-1 when reviewing its nomination, placing it in Category 2 before the nominators withdrew it.", "note": "Read what this finding is scoped to. It is about the COMPOUNDED BULK SUBSTANCE — immunogenicity by route, peptide-related impurities, and API characterisation — not about whether the molecule has ever been studied. FDA is describing what it does not know about material made outside an approved manufacturing process. A drug can have Phase 3 trials behind it and still leave FDA unable to characterise what a compounder would actually put in a vial. Those are different questions, and the market collapses them.", "source": { "url": "https://www.fda.gov/drugs/human-drug-compounding/certain-bulk-drug-substances-use-compounding-may-present-significant-safety-risks", "title": "Certain Bulk Drug Substances for Use in Compounding that May Present Significant Safety Risks", "publisher": "FDA", "date": "2026-04-22", "quote": "Compounded drugs containing thymosin-alpha-1 (Ta1) may pose significant risk for immunogenicity for certain routes of administration and may have complexities with regard to peptide-related impurities and API characterization. The safety-related information is inadequate for the agency to sufficiently understand the extent of any safety issues raised by the proposed compounded drug." }, "verifiedAt": "2026-07-16" }, { "finding": "FDA did NOT make its 'no human exposure data' finding for thymosin alpha-1, in contrast to five other withdrawn peptides on the same page.", "note": "The single most useful thing on this page is what it withholds. On the same withdrawn table, FDA writes that it 'has not identified any human exposure data' for dihexa acetate, KPV, PEG-MGF, MOTs-C and thymosin beta-4 fragment (TB-500). For thymosin alpha-1 it writes something materially weaker and different — that the safety information 'is inadequate for the agency to sufficiently understand the EXTENT of any safety issues'. Inadequate-to-quantify is not absent. FDA chose distinct language for distinct evidentiary situations, and flattening all withdrawn peptides into one 'FDA says there's no human data' claim misreports FDA on both ends: it overstates the record for TB-500's neighbours and understates it here.", "source": { "url": "https://www.fda.gov/drugs/human-drug-compounding/certain-bulk-drug-substances-use-compounding-may-present-significant-safety-risks", "title": "Certain Bulk Drug Substances for Use in Compounding that May Present Significant Safety Risks", "publisher": "FDA", "date": "2026-04-22" }, "verifiedAt": "2026-07-16" }, { "finding": "FDA's Pharmacy Compounding Advisory Committee voted 17 to 4 against placing thymosin alpha-1 (free base) on the 503A bulks list on December 4, 2024, and 17 to 4 against thymosin alpha-1 acetate.", "note": "The vote question was 'Should Thymosin alpha-1 (free base) be placed on the list?' — Yes: 4, No: 17, Abstain: 0. Identical tally for the acetate. Report the direction carefully: 17 voted AGAINST listing.\n\nThe four dissenting votes are the honest complication and are recorded here rather than buried. Per the minutes, SOME of the members voting in favour 'commented that this substance should be accessible to patients as an option for use' — an access argument, not an efficacy argument. Read the quantifier exactly: the minutes say 'Some Committee members who voted in favor', and they record no reasoning at all for the rest, so this is not the stated rationale of all four and must not be reported as though it were. What can be said is narrower and still holds: no member is recorded as arguing that the evidence established that it works. The committee's split, so far as the minutes disclose it, was about whether patients should be able to choose an unproven option, not about whether it was proven.", "source": { "url": "https://www.fda.gov/media/185642/download", "title": "Final Summary Minutes of the Pharmacy Compounding Advisory Committee Meeting, December 4, 2024", "publisher": "FDA", "date": "2024-12-04", "quote": "The majority of the Committee members voted against placing Thymosin alpha-1 (free base) on the 503A Bulks List. Several Committee members who voted \"No\" agreed there was no compelling evidence demonstrating clinical effectiveness and safety in the uses of Thymosin alpha-1 (free base) under review." }, "verifiedAt": "2026-07-16" }, { "finding": "FDA states directly that it has approved no drug product containing thymosin alpha-1, and identified a website marketing a compounded thymosin alpha-1 injectable as 'FDA-approved'.", "note": "Slide 12, under 'Historical Use in Compounding'. This is the rarest kind of primary source: FDA naming a specific marketing claim about this compound and contradicting it in the same sentence, in its own voice, on the record. Independently confirmed 2026-07-16 against the Drugs@FDA API, which returns no match for thymalfasin, Zadaxin or thymosin.\n\nThe same slide records that FDA found 'no evidence of compounded drug products containing Ta1 (free base) or Ta1 acetate in the published literature or in outsourcing facility reports', while compounded Ta1 is nonetheless 'marketed online in the United States' for hepatitis B, hepatitis C, HIV, chronic fatigue, inflammation, sepsis, COVID-19, Lyme disease, allergies, cancer, asthma, COPD and psoriatic arthritis. The gap between the indication list being sold and the evidence base FDA could locate is the whole story of this compound.", "source": { "url": "https://www.fda.gov/media/183892/download", "title": "Thymosin Alpha-1 (Ta1) Related Bulk Drug Substances — FDA presentation to the Pharmacy Compounding Advisory Committee", "publisher": "FDA", "date": "2024-12-04", "quote": "A website advertises a compounded SC injectable product that is \"FDA-approved\"; however, FDA has approved no drug products containing Ta1" }, "verifiedAt": "2026-07-16" }, { "finding": "FDA concluded there is a lack of evidence of effectiveness for thymosin alpha-1 across all twelve uses it evaluated, and that no US clinical practice guideline recommends it.", "note": "Slide 68, 'Overall Conclusion on Effectiveness'. The twelve evaluated uses were hepatitis B, hepatitis C, HIV, COVID-19, depressed vaccine response / influenza vaccine adjuvant, malignant melanoma, hepatocellular carcinoma, non-small cell lung cancer, sepsis, infections after haematopoietic stem cell transplantation, COPD, and ME/CFS. FDA published a separate written conclusion for each. Not one came out positive.\n\nThis is the finding that makes the 'thymosin alpha-1 is an immune-support peptide' marketing frame unanswerable rather than merely unsupported. FDA did not fail to look. It looked twelve times, in the indications the nominators themselves chose, and reported the same answer twelve times.", "source": { "url": "https://www.fda.gov/media/183892/download", "title": "Thymosin Alpha-1 (Ta1) Related Bulk Drug Substances — FDA presentation to the Pharmacy Compounding Advisory Committee", "publisher": "FDA", "date": "2024-12-04", "quote": "Lack of evidence to support the effectiveness of SC Ta1 (free base) and Ta1 acetate for the evaluated uses ... None of the clinical practice guidelines for U.S. health professionals recommend Ta1 (free base) or Ta1 acetate ... Studies on the serious and life-threatening conditions considered in the evaluation of effectiveness of Ta1 were inconclusive and limited by small sample sizes and design deficiencies" }, "verifiedAt": "2026-07-16" }, { "finding": "FDA identified no clinical studies at all of thymosin alpha-1 in myalgic encephalomyelitis / chronic fatigue syndrome, one of the twelve uses for which it was nominated.", "note": "Slide 67, and the single most under-reported sentence about this compound. Chronic fatigue is one of the leading consumer marketing claims for thymosin alpha-1 — FDA lists it among the conditions compounded Ta1 is sold for online (slide 12) — and it is the one nominated use where FDA located ZERO studies. Note the scope precisely: this is an evidence-of-effectiveness finding confined to ME/CFS, not the 'no human exposure data' finding FDA made for KPV, MOTS-c and TB-500. Ta1 has abundant human exposure data; it has none in this indication.", "source": { "url": "https://www.fda.gov/media/183892/download", "title": "Thymosin Alpha-1 (Ta1) Related Bulk Drug Substances — FDA presentation to the Pharmacy Compounding Advisory Committee", "publisher": "FDA", "date": "2024-12-04", "quote": "FDA did not identify any clinical studies using Ta1 in subjects with ME/CFS. Conclusion: FDA did not identify any data to support the effectiveness of Ta1 in the treatment of ME/CFS." }, "verifiedAt": "2026-07-16" }, { "finding": "FDA recorded that there is no USP drug substance monograph for thymosin alpha-1, concluded that both thymosin alpha-1 free base and thymosin alpha-1 acetate are not well-characterized, and found that the nominated 3 mg/mL injectable strength exceeds the substance's measured water solubility of 2 mg/mL with no explanation offered.", "note": "Slides 8 and 9, quoted in document order — the solubility figure and the monograph absence are on slide 8 ('Physical and Chemical Characterization (1)'), the not-well-characterized conclusion and the strength-exceeds-solubility finding on slide 9. An earlier revision cited the whole thing to slide 9 and carried the monograph fact in prose only; the monograph absence is load-bearing for the compounding answer, so it is now inside the quote.\n\nProduct identification, not a regimen — this is what is in the vial, not what to do with it. The finding is quietly devastating and requires no regulatory expertise to evaluate: the nominators asked FDA to permit compounding a solution at a strength more concentrated than the molecule dissolves at, and did not say how. FDA also recorded that no certificate of analysis for Ta1 free base was included in the nomination, and that no impurity limits or testing results were reported from the public domain. The identical monograph finding is recorded for the acetate. This is the criterion on which the nomination was weakest, and it is entirely independent of whether the drug works.", "source": { "url": "https://www.fda.gov/media/183892/download", "title": "Thymosin Alpha-1 (Ta1) Related Bulk Drug Substances — FDA presentation to the Pharmacy Compounding Advisory Committee", "publisher": "FDA", "date": "2024-12-04", "quote": "Solubility in water up to 2 mg/mL ... No USP drug substance monograph ... Conclusion: Ta1 (free base) is not well-characterized ... The proposed concentration for injectable product (3 mg/mL) is greater than the solubility of Ta1 (free base) in water (2 mg/mL). No information was provided regarding how a greater solubility is achieved" }, "verifiedAt": "2026-07-16" }, { "finding": "FDA was unable to independently verify industry claims that thymosin alpha-1 is approved in numerous countries, and recorded that it is not approved in the United States, Japan, or Europe except Italy.", "note": "Slide 13. This retires the '30+ countries' talking point, which is the load-bearing claim in nearly every consumer article about this compound. Its provenance, per FDA, is a SPONSOR'S ANNUAL REPORT — SciClone Pharmaceuticals' 2014 filing, SciClone being the company that markets Zadaxin and funds studies of it. FDA notes it could not confirm those claims. An earlier revision of this record declined to assert the '30+ countries' figure because we had no source for it; the correct treatment turns out to be stronger than silence — FDA looked, and could not verify it either.\n\nThe three major regulators that publish transparent review dossiers are precisely the three where it is not approved.", "source": { "url": "https://www.fda.gov/media/183892/download", "title": "Thymosin Alpha-1 (Ta1) Related Bulk Drug Substances — FDA presentation to the Pharmacy Compounding Advisory Committee", "publisher": "FDA", "date": "2024-12-04", "quote": "FDA is unable to independently verify these claims of approval in all the specified countries ... Ta1 is not approved in the United States, Japan, or Europe (except Italy) ... Ta1 is not recognized in the European or Japanese Pharmacopoeias" }, "verifiedAt": "2026-07-16" }, { "finding": "FDA elected to complete its evaluation of thymosin alpha-1 and take it to the advisory committee even after the nominators withdrew the nomination.", "note": "Footnote 5 of the briefing document, and the direct refutation of the loudest claim in the July 2026 peptide-legalisation content wave. The market's inference runs: nomination withdrawn, therefore removed from Category 2, therefore FDA's objection evaporated, therefore compoundable. Every step is wrong, and this footnote breaks the chain at the second one. FDA did not drop the substance when the nominators walked. It finished the review at its own discretion, presented it, and recommended against listing — and the committee agreed 17-4. Withdrawal removed the nominator, not the finding. The evaluation slides make the same point in their own words: 'The nomination was withdrawn, and FDA is evaluating the substances at its discretion.'", "source": { "url": "https://www.fda.gov/media/183583/download", "title": "FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, December 4, 2024", "publisher": "FDA", "date": "2024-12-04", "quote": "This nomination was withdrawn by the nominator (FDA-2015-N-3534-0470). However, FDA is electing to proceed with the presentation of thymosin alpha-1-related bulk drug substances (thymosin alpha-1 (free base) and thymosin alpha-1 acetate) to the PCAC." }, "verifiedAt": "2026-07-16" } ], "safetySignals": [ { "signal": "FDA: safety-related information inadequate to understand the extent of safety issues; immunogenicity risk for certain routes, plus peptide-related impurity and API characterisation complexities.", "note": "'Inadequate information' is not a clean bill of health, and the presence of Phase 3 trials does not answer it. Trials used a characterised, manufactured product; the nomination concerned bulk substance for compounding. Evidence of efficacy in a trial does not transfer to the safety of an uncharacterised bulk API.", "source": { "url": "https://www.fda.gov/drugs/human-drug-compounding/certain-bulk-drug-substances-use-compounding-may-present-significant-safety-risks", "title": "Certain Bulk Drug Substances for Use in Compounding that May Present Significant Safety Risks", "publisher": "FDA", "date": "2026-04-22" }, "verifiedAt": "2026-07-16" }, { "signal": "In the 2025 TESTS Phase 3 trial, a prespecified subgroup analysis showed a potential differential effect by age, with a hazard ratio of 1.67 (95% CI 1.04-2.67) for 28-day all-cause mortality in participants under 60 (P for interaction = 0.01).", "note": "Handle with care in both directions. This is a SUBGROUP finding from a trial whose primary outcome was null, the confidence interval barely excludes 1.0, and subgroup effects from null trials are unreliable and frequently do not replicate — this is not evidence that the drug kills young people. But it is the direction that should give the consumer market pause: the point estimate in the YOUNGER half favoured placebo, and the younger, healthier, non-septic user is precisely who buys this peptide for 'immune support'. An earlier revision added 'researchers reported it as hypothesis-generating' — that characterisation is not in the paper's abstract and we could not verify it in the full text (HTTP 403), so it is removed rather than softened. It also cut the wrong way: the analysis was PRESPECIFIED, which is the opposite of a fishing expedition, and calling it hypothesis-generating quietly discounted a signal unfavourable to the compound. The caution about subgroup findings from null trials stands on its own without putting words in the authors' mouths. Note also that the same prespecified analysis reported a differential effect by diabetes status in the opposite direction (diabetes: 0.58, 0.35 to 0.99; no diabetes: 1.16, 0.87 to 1.53; P for interaction=0.04) — which is itself the best evidence that these subgroup splits should not be read as findings. The honest summary is that the one large rigorous trial that looked found no benefit overall and nothing reassuring for younger recipients.", "source": { "url": "https://pubmed.ncbi.nlm.nih.gov/39814420/", "title": "The efficacy and safety of thymosin α1 for sepsis (TESTS): multicentre, double blinded, randomised, placebo controlled, phase 3 trial", "publisher": "BMJ", "date": "2025-01-15" }, "verifiedAt": "2026-07-16" }, { "signal": "FDA's PCAC evaluation records fatal immune haemolytic anaemia and engraftment failure in stem-cell transplant recipients among adverse events reported in thymosin alpha-1 studies, and flags that thymosin alpha-1 could cause or worsen graft-versus-host disease in patients undergoing deliberate immunosuppression.", "note": "Slides 20, 21 and 24. Scope this correctly rather than sensationally. FDA's overall clinical-safety conclusion is comparatively mild — in most studies Ta1 'has not been associated with significant adverse events attributable to Ta1', with the most common reactions being local irritation, redness or discomfort at the injection site. The haemolytic-anaemia and engraftment-failure events come from a single small transplant study (Perruccio et al. 2010) in profoundly immunocompromised patients, which is not the consumer population.\n\nThe transferable point is mechanistic, and it is the one the 'immune support' framing obscures: FDA's concern is that an immunomodulator can act in the direction you did not want. In a transplant recipient, stimulating immunity is how you get graft-versus-host disease. FDA raises the same structural worry about using it alongside influenza vaccines, where it notes that 'adding an immunomodulatory product such as Ta1 to any vaccine could pose unknown safety concerns that warrant further evaluation'. A drug marketed as boosting the immune system is a drug that can perturb it, and FDA's stated position is that it lacks the information to know when.", "source": { "url": "https://www.fda.gov/media/183892/download", "title": "Thymosin Alpha-1 (Ta1) Related Bulk Drug Substances — FDA presentation to the Pharmacy Compounding Advisory Committee", "publisher": "FDA", "date": "2024-12-04", "quote": "Potential safety concerns with administering Ta1 in patients who are undergoing deliberate immunosuppression. For example, Ta1 could cause or worsen acute or chronic graft-vs-host disease (GVHD) and lead to engraftment failure in HSCT recipients." }, "verifiedAt": "2026-07-16" } ], "faqs": [ { "question": "Did FDA approve thymosin alpha-1?", "answer": "No. FDA has approved no drug product containing thymosin alpha-1. In its December 2024 evaluation of the substance, FDA noted that a website advertises a compounded thymosin alpha-1 injectable as \"FDA-approved\" and stated in response that \"FDA has approved no drug products containing Ta1\". A search of the Drugs@FDA database on 2026-07-16 returned no approved product under the names thymalfasin, Zadaxin or thymosin. The brand name Zadaxin is marketed only outside the United States.", "source": { "url": "https://www.fda.gov/media/183892/download", "title": "Thymosin Alpha-1 (Ta1) Related Bulk Drug Substances — FDA presentation to the Pharmacy Compounding Advisory Committee", "publisher": "FDA", "date": "2024-12-04", "quote": "A website advertises a compounded SC injectable product that is \"FDA-approved\"; however, FDA has approved no drug products containing Ta1" }, "verifiedAt": "2026-07-16" }, { "question": "Did thymosin alpha-1 become legal again when FDA removed it from Category 2?", "answer": "No. Thymosin alpha-1 left Category 2 because the nominators withdrew the nomination, not because FDA resolved its concerns, and it did not become compoundable as a result. FDA continued the review anyway: its briefing document records that although \"this nomination was withdrawn by the nominator\", FDA was \"electing to proceed with the presentation of thymosin alpha-1-related bulk drug substances ... to the PCAC\". On December 4, 2024 FDA proposed that thymosin alpha-1 not be added to the 503A bulks list and the advisory committee voted 17 to 4 against adding it. Thymosin alpha-1 does not appear on the 503A bulks list updated May 14, 2026, and remains non-compoundable in the United States.", "source": { "url": "https://www.fda.gov/media/183583/download", "title": "FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, December 4, 2024", "publisher": "FDA", "date": "2024-12-04", "quote": "This nomination was withdrawn by the nominator (FDA-2015-N-3534-0470). However, FDA is electing to proceed with the presentation of thymosin alpha-1-related bulk drug substances (thymosin alpha-1 (free base) and thymosin alpha-1 acetate) to the PCAC." }, "verifiedAt": "2026-07-16" }, { "question": "Is there any human evidence that thymosin alpha-1 works?", "answer": "Yes — thymosin alpha-1 has genuinely been given to humans in large, well-designed trials, which is unusual for a peptide sold online. The largest is a double blinded, placebo controlled Phase 3 trial in 1,106 adults with sepsis across 22 centres in China, published in The BMJ in 2025. It did not find a benefit. Researchers reported 28-day all-cause mortality of 23.4% in the thymosin alpha-1 group versus 24.1% with placebo (hazard ratio 0.99, 95% confidence interval 0.77 to 1.27; P=0.93), reported that no secondary or safety outcome differed statistically significantly between the groups, and concluded there was \"no clear evidence to suggest that thymosin α1 decreases 28 day all cause mortality in adults with sepsis\". The accurate summary is that thymosin alpha-1 was properly tested and the trial came back negative, which is a different thing from untested — and a different thing from proven.", "source": { "url": "https://pubmed.ncbi.nlm.nih.gov/39814420/", "title": "The efficacy and safety of thymosin α1 for sepsis (TESTS): multicentre, double blinded, randomised, placebo controlled, phase 3 trial", "publisher": "BMJ", "date": "2025-01-15", "quote": "This trial found no clear evidence to suggest that thymosin α1 decreases 28 day all cause mortality in adults with sepsis." }, "verifiedAt": "2026-07-16" }, { "question": "Did thymosin alpha-1 work in the hepatitis C trial?", "answer": "No, not for treating the infection. A Phase 3 trial published in 2012 randomised 552 patients with chronic hepatitis C who had not responded to peginterferon plus ribavirin to receive either thymosin alpha-1 or placebo alongside standard care. Researchers reported sustained viral response rates in the intention-to-treat population that were \"similar between thymosin alpha-1 and placebo (12.7%vs 10.5%; P = 0.407)\" and concluded that \"Thymosin alpha-1 seems to play no role in the primary therapy of the disease\". A higher response rate did appear among the subset of patients who completed all 48 weeks of therapy (41.0% versus 26.3%, P = 0.048), but a completer analysis discards the randomisation that made the trial informative, and the authors framed it as raising a hypothesis about a possible secondary adjuvant role rather than as a result. This trial is why the plural in \"Phase 3 trials\" is accurate: two independent programmes, two negative primary endpoints.", "source": { "url": "https://pubmed.ncbi.nlm.nih.gov/22233415/", "title": "Thymosin alpha-1 with peginterferon alfa-2a/ribavirin for chronic hepatitis C not responsive to IFN/ribavirin: an adjuvant role?", "publisher": "Journal of Viral Hepatology", "date": "2012-01-01", "quote": "SVR rates in the intention to treat population were similar between thymosin alpha-1 and placebo (12.7%vs 10.5%; P = 0.407) ... The addition of thymosin alpha-1 to the standard of care did not increase the on-treatment HCV viral response. Thymosin alpha-1 seems to play no role in the primary therapy of the disease." }, "verifiedAt": "2026-07-16" }, { "question": "Do the meta-analyses showing thymosin alpha-1 reduces sepsis mortality prove it works?", "answer": "No, and the clearest statement of why comes from a meta-analysis itself. A 2025 systematic review pooled 11 randomised controlled trials of thymosin alpha-1 in sepsis (967 patients in the thymosin alpha-1 group, 960 in the control group) and did report a statistically significant reduction in 28-day mortality (odds ratio 0.73, 95% CI 0.59-0.90, P = 0.003) — the number vendors cite. The same authors then reported that the effect disappeared when they restricted the analysis to high-quality trials (OR 0.82, 95% CI 0.65-1.03, P = 0.09) and to multi-center trials (OR 0.86, 95% CI 0.68-1.08, P = 0.20). A pooled benefit that evaporates as trial quality rises is a description of the low-quality trials, not of the drug. This is consistent with the largest and most rigorous individual trial, the 1,106-patient BMJ trial, which found no benefit.", "source": { "url": "https://pubmed.ncbi.nlm.nih.gov/40969554/", "title": "Efficacy of thymosin α1 for sepsis: a systematic review and meta-analysis of randomized controlled trials", "publisher": "Frontiers in Cellular and Infection Microbiology", "date": "2025-09-03", "quote": "Out of 3003 identified studies, 11 RCTs met the inclusion criteria (967 patients in Tα1 group and 960 patients in control group). The comprehensive meta-analysis demonstrated a significant reduction in 28-day mortality associated with Tα1 administration (OR 0.73, 95%CI: 0.59-0.90, P = 0.003). Nonetheless, analyses of high-quality (OR 0.82, 95%CI: 0.65-1.03, P = 0.09) and multi-center (OR 0.86, 95%CI: 0.68-1.08, P = 0.20) subgroups did not reveal a mortality benefit." }, "verifiedAt": "2026-07-16" }, { "question": "Is thymosin alpha-1 approved in 30 countries?", "answer": "FDA could not verify the foreign-approval claims it was given, and did not itself state any country count. What FDA reviewed in December 2024 was SciClone Pharmaceuticals' 2014 Annual Report — SciClone being the company that funds studies of its thymosin alpha-1 product Zadaxin — which said thymosin alpha-1 was \"approved\" in countries in the Asia-Pacific region, Latin America, Eastern Europe and the Middle East. FDA wrote that it \"is unable to independently verify these claims of approval in all the specified countries\", and recorded that thymosin alpha-1 \"is not approved in the United States, Japan, or Europe (except Italy)\" and \"is not recognized in the European or Japanese Pharmacopoeias\". So the honest answer is that the number is a sponsor's claim no regulator has confirmed, and that the three major regulators which publish transparent review dossiers are precisely the ones where it is not approved. A marketing authorisation from another country is also not an FDA approval and does not make a substance eligible for compounding in the United States.", "source": { "url": "https://www.fda.gov/media/183892/download", "title": "Thymosin Alpha-1 (Ta1) Related Bulk Drug Substances — FDA presentation to the Pharmacy Compounding Advisory Committee", "publisher": "FDA", "date": "2024-12-04", "quote": "According to the SciClone Pharmaceuticals' 2014 Annual Report, Ta1 is \"approved\" for use in countries in the Asia-Pacific region, Latin America, Eastern Europe, and the Middle East ... FDA is unable to independently verify these claims of approval in all the specified countries ... Ta1 is not approved in the United States, Japan, or Europe (except Italy) ... Ta1 is not recognized in the European or Japanese Pharmacopoeias" }, "verifiedAt": "2026-07-16" }, { "question": "Can I get thymosin alpha-1 from a compounding pharmacy?", "answer": "Not lawfully. FDA's guidance on compounding under section 503A of the Federal Food, Drug, and Cosmetic Act sets out three doors a bulk drug substance can come through: it must comply with an applicable USP or NF monograph if one exists; or, if no monograph exists, be a component of a drug approved by the Secretary; or, if neither, appear on the 503A bulks list developed by regulation. Thymosin alpha-1 comes through none of them — FDA's December 2024 evaluation records that there is no USP drug substance monograph for it and that FDA has approved no drug products containing it, and it does not appear in Category 1, 2 or 3 of the 503A list updated May 14, 2026. Each of those three facts is documented separately on this page. FDA has also noted that compounded thymosin alpha-1 is nonetheless marketed online in the United States, including by at least one website describing it as FDA-approved.", "source": { "url": "https://www.fda.gov/media/174456/download", "title": "Interim Policy on Compounding Using Bulk Drug Substances Under Section 503A of the Federal Food, Drug, and Cosmetic Act — Guidance for Industry", "publisher": "FDA", "date": "2025-01-07", "quote": "One of the conditions that must be met for a compounded drug product to qualify for these exemptions is that a licensed pharmacist or licensed physician compounds the drug product using bulk drug substances that: (1) Comply with the standards of an applicable United States Pharmacopeia (USP) or National Formulary (NF) monograph, if a monograph exists, and the USP chapter on pharmacy compounding; (2) If such a monograph does not exist, are drug substances that are components of drugs approved by the Secretary of the Department of Health and Human Services (Secretary); or (3) If such a monograph does not exist and the drug substance is not a component of a drug approved by the Secretary, appears on a list developed by the Secretary through regulations issued by the Secretary under subsection (c) of section 503A." }, "verifiedAt": "2026-07-16" }, { "question": "What did FDA's advisory committee decide about thymosin alpha-1?", "answer": "FDA's Pharmacy Compounding Advisory Committee voted 17 to 4 against placing thymosin alpha-1 on the 503A bulks list at its meeting on December 4, 2024, with the same 17-4 tally for both the free base and the acetate form. According to the meeting's final summary minutes, several members voting against \"agreed there was no compelling evidence demonstrating clinical effectiveness and safety in the uses of Thymosin alpha-1 (free base) under review\", while some of the members who voted in favour commented that the substance \"should be accessible to patients as an option for use\" — an access argument rather than a claim that it had been shown to work. FDA had proposed that thymosin alpha-1 not be included on the list, and the committee agreed.", "source": { "url": "https://www.fda.gov/media/185642/download", "title": "Final Summary Minutes of the Pharmacy Compounding Advisory Committee Meeting, December 4, 2024", "publisher": "FDA", "date": "2024-12-04", "quote": "The majority of the Committee members voted against placing Thymosin alpha-1 (free base) on the 503A Bulks List. Several Committee members who voted \"No\" agreed there was no compelling evidence demonstrating clinical effectiveness and safety in the uses of Thymosin alpha-1 (free base) under review." }, "verifiedAt": "2026-07-16" } ] }, { "slug": "tirzepatide", "name": "Tirzepatide", "aliases": [ "Mounjaro", "Zepbound", "LY3298176", "Mounjaro KwikPen", "Zepbound KwikPen" ], "url": "https://peptides101.com/compounds/tirzepatide", "moleculeNote": "A synthetic 39-amino-acid peptide; a dual glucose-dependent insulinotropic polypeptide (GIP) receptor and glucagon-like peptide-1 (GLP-1) receptor agonist. The disambiguation that matters here is not between two molecules but between two PRODUCTS. FDA-approved tirzepatide (Eli Lilly; NDA 215866 / NDA 217806; prescription-only) and the 'research use only' tirzepatide sold by peptide vendors are regulated as entirely different things: FDA told USApeptide.com that although 'there are FDA-approved tirzepatide products on the market in the U.S., there are no approved drug applications … in effect for' the products it was selling. The clinical evidence below attaches to the approved product only. Nothing in it transfers to an unapproved vial of unverified identity, purity or content.", "quickAnswer": "Tirzepatide is an FDA-approved prescription drug: Eli Lilly's Mounjaro (NDA 215866), for glycemic control in adults and pediatric patients 10 years and older with type 2 diabetes, and Zepbound (NDA 217806), for weight reduction in adults with obesity or overweight with at least one weight-related comorbid condition and for moderate to severe obstructive sleep apnea in adults with obesity — both carrying a boxed warning about thyroid C-cell tumors seen in rats, whose relevance to humans the labeling says has not been determined. That approval belongs to those two applications and not to the molecule: FDA told USApeptide.com in February 2025 that although there are FDA-approved tirzepatide products on the market, there are 'no approved drug applications … in effect for' the tirzepatide it was selling, and in May 2026 FDA proposed not to add tirzepatide to the 503B Bulks List — finding no reason outsourcing facilities need to compound it rather than use the approved product, which FDA recorded is not on the drug shortage list.", "fdaStatus": { "value": "approved", "note": "FDA-approved. Approval is always for a specific indication and population — see the approval record below, because it is routinely not the use this is marketed for.", "source": { "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2026/215866s009lbl.pdf", "title": "MOUNJARO (tirzepatide) injection — Highlights of Prescribing Information", "publisher": "FDA", "date": "2026-04-22" }, "verifiedAt": "2026-07-16" }, "compoundingStatus": null, "evidence": { "tier": "proven-in-humans", "humanAdministrationChecked": true, "note": "ADMINISTRATION CHECK RUN AND PASSED — genuinely, which is rare in this library. Two pivotal trials were opened individually and confirmed to ADMINISTER tirzepatide rather than measure an endogenous peptide as a biomarker: SURMOUNT-1 (NCT04184622, Phase 3, n=2,539, sponsor Eli Lilly, COMPLETED, results first posted 2023-04-24; ClinicalTrials.gov lists the intervention as DRUG Tirzepatide 'Administered SC') and SURPASS-2 (NCT03987919, Phase 3, n=1,879, COMPLETED, results first posted 2022-02-14). In the 2022 SURMOUNT-1 trial of 2,539 adults with obesity or overweight with a weight-related complication and without diabetes, researchers reported a mean weight change at week 72 ranging from -15.0% to -20.9% across the three tirzepatide dose arms versus -3.1% with placebo. In the 2021 SURPASS-2 trial of 1,879 patients with type 2 diabetes, researchers reported HbA1c reductions of -2.01 to -2.30 percentage points across the tirzepatide arms versus -1.86 with the semaglutide comparator. Limitations: SURPASS-2 was open-label; both trials were sponsored by the manufacturer; SURMOUNT-1 excluded people with diabetes, so its weight results do not transfer to that population; and neither trial tested any compounded, oral, sublingual or vendor-supplied preparation. The tier is scoped to the APPROVED INDICATIONS via the APPROVED PRODUCT — it is not a finding about tirzepatide from any other source, at any other dose, by any other route. COUNTING TRAP, INVERTED: the raw registry count for tirzepatide is large, and a count is still not a tier. At least one registration in that count is fraudulent. NCT07481747 was opened and inspected: it carries the SAME official title and the SAME enrollment figure (2,539) as the real SURMOUNT-1, but its sponsor is 'Hudson Biotech', its start date is 2026-02-02, its status is RECRUITING and it has no results — a verbatim clone of a trial Lilly completed and published in 2022. It is not cited here and is not evidence of anything except registry contamination.", "source": { "url": "https://pubmed.ncbi.nlm.nih.gov/35658024/", "title": "Tirzepatide Once Weekly for the Treatment of Obesity (SURMOUNT-1)", "publisher": "The New England Journal of Medicine", "date": "2022-07-21", "quote": "we assigned 2539 adults … in a 1:1:1:1 ratio to receive once-weekly, subcutaneous tirzepatide … or placebo …" }, "verifiedAt": "2026-07-16" }, "fdaApproval": { "applicationNumber": "NDA 215866 (Mounjaro); NDA 217806 (Zepbound)", "brandName": "Mounjaro; Zepbound", "approvedIndication": "MOUNJARO (NDA 215866), verbatim: 'a glucose-dependent insulinotropic polypeptide (GIP) receptor and glucagon-like peptide-1 (GLP-1) receptor agonist indicated as an adjunct to diet and exercise to improve glycemic control in adults and pediatric patients 10 years of age and older with type 2 diabetes mellitus.' ZEPBOUND (NDA 217806), verbatim: 'indicated in combination with a reduced-calorie diet and increased physical activity: to reduce excess body weight and maintain weight reduction long term in adults with obesity or adults with overweight in the presence of at least one weight-related comorbid condition[;] to treat moderate to severe obstructive sleep apnea (OSA) in adults with obesity.' Zepbound's labeling adds a Limitation of Use: 'Coadministration with other tirzepatide-containing products or with any GLP-1 receptor agonist is not recommended.'", "discontinued": false, "source": { "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2026/215866s009lbl.pdf", "title": "MOUNJARO (tirzepatide) injection — Highlights of Prescribing Information", "publisher": "FDA", "date": "2026-04-22" }, "verifiedAt": "2026-07-16" }, "fdaFindings": [ { "finding": "FDA proposes NOT to include tirzepatide on the 503B Bulks List, alongside semaglutide and liraglutide, having tentatively found no attribute of the FDA-approved tirzepatide products that makes them medically unsuitable for any patient.", "note": "This is section 503B (outsourcing facilities), a DIFFERENT statute from the 503A bulks list that governs the rest of this library — do not merge the two. The proposal is also not final: comments were due 2026-06-30. FDA's stated reason is narrow and worth quoting exactly, because it is the opposite of a safety finding: 'For these reasons, FDA tentatively finds no basis to conclude that there is an attribute of the FDA-approved drug products containing tirzepatide that makes them medically unsuitable to treat certain patients for a condition that FDA has identified for evaluation …' The approved drug being adequate is the reason compounding was refused.", "source": { "url": "https://www.govinfo.gov/content/pkg/FR-2026-05-01/html/2026-08552.htm", "title": "List of Bulk Drug Substances for Which There Is a Clinical Need Under Section 503B of the Federal Food, Drug, and Cosmetic Act (Docket No. FDA-2018-N-3240)", "publisher": "Federal Register / FDA", "date": "2026-05-01", "quote": "This notice identifies three bulk drug substances that FDA has considered and proposes not to include on the 503B Bulks List: semaglutide, tirzepatide, and liraglutide." }, "verifiedAt": "2026-07-16" }, { "finding": "FDA rejected the nominators' arguments for compounded oral, sublingual and buccal tirzepatide, stating that the statutory standard is clinical need — not preference.", "note": "Directly relevant to the oral and sublingual 'tirzepatide' products sold online: FDA notes that 'no tirzepatide drug product is approved in these routes of administration' and declined to find a clinical need for them. FDA likewise rejected proposals for concentrations exceeding the approved product (20 mg/0.5 mL and 30 mg/0.5 mL), observing that the nominations 'do not provide supporting data or information' for them and that 'obtaining a better response with a higher dose does not mean that the approved product does not achieve the intended clinical benefit'.", "source": { "url": "https://www.govinfo.gov/content/pkg/FR-2026-05-01/html/2026-08552.htm", "title": "List of Bulk Drug Substances for Which There Is a Clinical Need Under Section 503B of the Federal Food, Drug, and Cosmetic Act (Docket No. FDA-2018-N-3240)", "publisher": "Federal Register / FDA", "date": "2026-05-01", "quote": "the statutory standard for inclusion of a substance on the 503B Bulks List is clinical need--not ``preference.''" }, "verifiedAt": "2026-07-16" }, { "finding": "FDA rejected drug shortage as a basis for compounding tirzepatide from bulk substance, and recorded that FDA-approved tirzepatide products are not on the drug shortage list.", "note": "The shortage that supported the 2023-2024 compounded-GLP-1 market is over, and FDA says so in the notice: it 'does not interpret such issues, such as shortages and backorders, to be within the meaning of clinical need'. Eli Lilly filed a comment (FDA-2015-N-3469-0404, 2024-11-04) opposing the nomination. Any vendor still invoking shortage as its legal basis in 2026 is invoking a fact that is no longer true.", "source": { "url": "https://www.govinfo.gov/content/pkg/FR-2026-05-01/html/2026-08552.htm", "title": "List of Bulk Drug Substances for Which There Is a Clinical Need Under Section 503B of the Federal Food, Drug, and Cosmetic Act (Docket No. FDA-2018-N-3240)", "publisher": "Federal Register / FDA", "date": "2026-05-01", "quote": "We also note that as of the date of this notice, FDA-approved tirzepatide drug products are not on the FDA drug shortage list." }, "verifiedAt": "2026-07-16" }, { "finding": "FDA warned USApeptide.com that its tirzepatide products are unapproved new drugs and misbranded, and cited the site's own research-framed marketing sentences as the evidence of intended use.", "note": "The exhibit for this site's house style. FDA listed the sentences 'Tirzepatide is a compound that has been shown to help with weight loss…' and '… recently approved in the US to help type 2 diabetes patients better manage blood sugar' as the evidence of intended use that made the products unapproved new drugs. Both sentences are TRUE of the approved product, and citing the approved drug's real evidence is precisely what converted the vendor's vial into an unapproved new drug — accuracy about the molecule is not a defence when the product is not the approved one. FDA also noted the products 'are intended for injection, which heightens the public health concern'.", "source": { "url": "https://www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/warning-letters/usapeptidecom-696885-02262025", "title": "Warning Letter — USApeptide.com (696885)", "publisher": "FDA", "date": "2025-02-26", "quote": "While there are FDA-approved tirzepatide products on the market in the U.S., there are no approved drug applications pursuant to section 505 of the FD&C Act in effect for the 5mg Tirzepatide (Mounjaro) 5mg\" and \"10mg Tirzepatide (Mounjaro) 10mg\" offered by www.usapeptide.com." }, "verifiedAt": "2026-07-16" }, { "finding": "FDA inspected a Chinese supplier of tirzepatide API to the U.S. market in November 2025 and found its APIs adulterated, recording that the firm shipped lots of tirzepatide API to the United States in 2024 without completing analytical method validation for assay, related substances, high molecular weight aggregates and amino acid ratio, and in 2025 without completing method verification for the bacterial endotoxin test.", "note": "The single most useful document on this record, because it is the only one that opens the vial. Harbin Jixianglong Biotech Co., Ltd. (FEI 3024038751) was inspected 2025-11-03/07; FDA concluded that because its 'methods, facilities, or controls … do not conform to CGMP, your APIs are adulterated within the meaning of section 501(a)(2)(B)'. Read the specific gaps for what each one is a test FOR: assay is how much tirzepatide is present; related substances and high molecular weight aggregates are what ELSE is present; amino acid ratio is whether the peptide is the right peptide at all; bacterial endotoxin is whether it will cause a febrile reaction when injected. None of the four was validated for material already in the United States. FDA further found the related-substance method validation itself deficient, citing 'poor resolution, overlapping peaks, and absence of structural identification' for specified impurities, and noted the firm's non-sterile tirzepatide API 'are intended for sterile injectable drug products' while its process water 'has not been evaluated for the absence of objectionable microorganisms'. The firm's own response is the finding's sharpest line: it acknowledged 'that your semaglutide and tirzepatide API drugs are in the development stage and full validation of all analytical methods has yet to be completed.' FDA rejected the R&D framing on volume — 'the quantity of API drugs … shipped into the U.S. is inconsistent with quantities typically used for research and development purposes.' SCOPE, honestly: this is ONE named supplier on ONE inspection. It does not establish that all gray-market tirzepatide is contaminated, and this record does not claim that. What it establishes is narrower and harder to argue with — that for at least some tirzepatide API entering the U.S., the tests that would answer 'is this tirzepatide, and only tirzepatide' had not been run.", "source": { "url": "https://www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/warning-letters/harbin-jixianglong-biotech-co-ltd-723330-05012026", "title": "Warning Letter 320-26-73 — Harbin Jixianglong Biotech Co., Ltd. (723330)", "publisher": "FDA", "date": "2026-05-01", "quote": "in 2024 your firm shipped (b)(4) lots of tirzepatide API (about (b)(4) total weight) to the U.S. market without completing analytical method validation for assay and related substances by high-performance liquid chromatography, high molecular weight aggregates by size-exclusion chromatography, and amino acid ratio by high-performance liquid chromatography." }, "verifiedAt": "2026-07-16" }, { "finding": "FDA placed GLP-1 API drugs under Import Alert 66-80 with a 'Green List' on September 5, 2025, subjecting GLP-1 APIs from facilities not on that list to detention without physical examination at the U.S. border.", "note": "A border control, not a quality certificate, and the same letter shows why the distinction is not academic. Harbin was ON the Green List (added 2025-09-05 on previously provided quality information) and nonetheless bought GLP-1 API from a facility that was not, relabeled it as its own — changing the manufacturer name, the manufacturing date and the retest date — and shipped it to the United States. FDA's conclusion, verbatim: 'identifying your firm and not the actual manufacturers may have been an attempt to circumvent safeguards associated with IA 66-80 and may pose a risk to consumers of receiving substandard GLP-1 APIs.' Those relabeled batches were semaglutide; the point that survives for tirzepatide is structural — presence on the Green List is a statement about a facility, not about the material in any given drum, and the chain of custody behind a gray-market vial is exactly what the inspection found was not documented.", "source": { "url": "https://www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/warning-letters/harbin-jixianglong-biotech-co-ltd-723330-05012026", "title": "Warning Letter 320-26-73 — Harbin Jixianglong Biotech Co., Ltd. (723330)", "publisher": "FDA", "date": "2026-05-01", "quote": "on September 5, 2025, FDA implemented the Green List of Import Alert 66-80 to help address GLP-1 API drugs offered for import into the United States that appear to be adulterated or misbranded." }, "verifiedAt": "2026-07-16" }, { "finding": "FDA warned Gram Peptides that the product it sells as 'GLP-2 Peptide' is tirzepatide, and that it is an unapproved new drug.", "note": "Worth recording because the renaming is a live source of confusion rather than a curiosity: GLP-2 is a real and DIFFERENT endogenous peptide, and tirzepatide is not it — tirzepatide is a dual GIP/GLP-1 receptor agonist. FDA identified the product under the vendor's label as tirzepatide anyway, which is the operative point: a house name does not change what the product is or what law applies to it. FDA cited the listing's own text as the evidence of intended use, including the claim that 'GLP-2 Peptide' is '[a]ssociated with significant decreases in body weight in both animal and human studies'. The same letter records that the RUO framing failed: 'Despite statements on your product labeling marketing your products for \"Research Use Only,\" and \"not intended for human consumption, medical use, or veterinary use,\" evidence obtained from your website establishes that your products are intended to be drugs for human use.'", "source": { "url": "https://www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/warning-letters/gram-peptides-721806-03312026", "title": "Warning Letter — Gram Peptides (721806)", "publisher": "FDA", "date": "2026-03-31", "quote": "The FDA has observed that your website offers \"Retatrutide\" (also referred to by your firm as \"GLP-1-R peptide\") and \"Tirzepatide\" (also referred to by your firm as \"GLP-2 peptide\") … for sale in the United States." }, "verifiedAt": "2026-07-16" }, { "finding": "FDA warned a second vendor, Lovega LLC dba Pink Pony Peptides, that the product it sells as 'GLP-2 TZ' is an unapproved new drug, citing as evidence of intended use the listing's own text describing tirzepatide as a dual GIP and GLP-1 receptor agonist.", "note": "The same house-naming pattern as the Gram Peptides letter, from a different firm on the same day — which is why it is recorded separately rather than folded into that finding. The scope difference is worth keeping straight: in the Gram letter FDA itself identified the product as tirzepatide ('also referred to by your firm as \"GLP-2 peptide\"'). Here FDA does not make that identification in its own voice; it quotes the vendor's own listing, which names Tirzepatide and describes it as 'a dual GIP and GLP-1 receptor agonist'. FDA recorded that the RUO framing failed here too: 'Despite statements on your product labeling marketing your products for \"laboratory research purposes only\" and \"[n]ot for human consumption,\" evidence obtained from your website establishes that your products are intended to be drugs for human use.' FDA also noted that injectable products 'bypass some of the body's key defenses against toxins and microorganisms'.", "source": { "url": "https://www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/warning-letters/lovega-llc-dba-pink-pony-peptides-721088-03312026", "title": "Warning Letter — Lovega LLC dba Pink Pony Peptides (721088)", "publisher": "FDA", "date": "2026-03-31", "quote": "The FDA has observed that your website offers \"GLP-2 TZ,\" \"GLP-3 RT,\" and \"Bacteriostatic Water\" (hereinafter Pink Pony Peptides products) for sale in the United States. Based on our review, these products are unapproved new drugs under section 505(a) of the Federal Food, Drug, and Cosmetic Act (FD&C Act), 21 U.S.C. 355(a)." }, "verifiedAt": "2026-07-16" }, { "finding": "FDA declined to find a clinical need to compound tirzepatide for the nominators' proposed use of 'related health conditions as determined appropriate by medical provider', because the conditions were never identified.", "note": "The open-ended clause is the compounding industry's version of the off-label market for this drug, and FDA answered it in one line. The same section disposes of the cardiovascular indication the nominators sought — 'the nominator did not provide any supporting data or information for this use' — and of the proposal to compound tirzepatide combined with pyridoxine or an antiemetic, where FDA observed the nominations 'do not even identify which antiemetic would be included in the compounded product.' A pattern runs through all of it and is the honest summary of the notice: FDA did not weigh the nominators' evidence and find it wanting. In each instance there was no evidence submitted to weigh.", "source": { "url": "https://www.govinfo.gov/content/pkg/FR-2026-05-01/html/2026-08552.htm", "title": "List of Bulk Drug Substances for Which There Is a Clinical Need Under Section 503B of the Federal Food, Drug, and Cosmetic Act (Docket No. FDA-2018-N-3240)", "publisher": "Federal Register / FDA", "date": "2026-05-01", "quote": "we cannot find that there is a clinical need for an outsourcing facility to compound tirzepatide for unidentified health conditions." }, "verifiedAt": "2026-07-16" } ], "safetySignals": [ { "signal": "Boxed warning — risk of thyroid C-cell tumors. The approved labeling's boxed warning states that in rats, tirzepatide causes dose-dependent and treatment-duration-dependent thyroid C-cell tumors at clinically relevant exposures, and that human relevance has not been determined.", "note": "FDA's strongest warning class, and it sits on the approved product with a prescriber, a Medication Guide and a contraindication screen attached. Contraindicated in patients with a personal or family history of MTC or with Multiple Endocrine Neoplasia syndrome type 2 — a screen that only happens if someone is doing the screening. FDA made this exact point to USApeptide.com: approved tirzepatide 'bears a boxed warning addressing the risk of thyroid C-Cell tumors', while the vendor's version shipped without one. Note the direction of the evidence: this is a rodent finding of undetermined human relevance, not a demonstrated human cancer risk. Overstating it is as much an error as omitting it.", "source": { "url": "https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=217806", "title": "ZEPBOUND (tirzepatide) injection — FDA-approved labeling, NDA 217806", "publisher": "FDA", "date": "2026-04-22", "quote": "It is unknown whether ZEPBOUND causes thyroid C-cell tumors, including medullary thyroid carcinoma (MTC), in humans as human relevance of tirzepatide-induced rodent thyroid C-cell tumors has not been determined" }, "verifiedAt": "2026-07-16" }, { "signal": "Boxed warning — risk of thyroid C-cell tumors, on the second application as well. Mounjaro's approved labeling carries the same boxed warning as Zepbound's, in the same terms: rodent thyroid C-cell tumors of undetermined human relevance.", "note": "Recorded separately rather than merged with the Zepbound signal above, because the two approvals are two documents and this record's whole argument is that approval attaches to an application rather than to a molecule — so 'both products carry it' has to be two sources saying it, not one source and an inference. Retrieved 2026-07-16 via the openFDA drug/label endpoint, NDA 215866, effective_time 20260422. Mounjaro is likewise contraindicated in patients with a personal or family history of MTC or with Multiple Endocrine Neoplasia syndrome type 2.", "source": { "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2026/215866s009lbl.pdf", "title": "MOUNJARO (tirzepatide) injection — Highlights of Prescribing Information", "publisher": "FDA", "date": "2026-04-22", "quote": "In both male and female rats, tirzepatide causes dose-dependent and treatment-duration-dependent thyroid C-cell tumors at clinically relevant exposures. It is unknown whether MOUNJARO causes thyroid C-cell tumors, including medullary thyroid carcinoma (MTC), in humans as human relevance of tirzepatide-induced rodent thyroid C-cell tumors has not been determined" }, "verifiedAt": "2026-07-16" }, { "signal": "Labeled warnings and precautions: acute pancreatitis; hypoglycemia with concomitant insulin or insulin secretagogues; serious hypersensitivity reactions including anaphylaxis and angioedema; acute kidney injury due to volume depletion; severe gastrointestinal adverse reactions; diabetic retinopathy complications; acute gallbladder disease; and pulmonary aspiration during general anesthesia or deep sedation.", "note": "From the approved labeling, sections 5.2-5.9, retrieved 2026-07-16. Most common adverse reactions (>=5%): nausea, diarrhea, decreased appetite, vomiting, constipation, dyspepsia and abdominal pain. Severe Gastrointestinal Adverse Reactions (5.6) is flagged as a Recent Major Change dated 12/2025, and the drug is not recommended in patients with severe gastroparesis. These are the risks of the drug taken correctly under supervision — they are the floor, not the ceiling, for a product of unverified identity and content.", "source": { "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2026/215866s009lbl.pdf", "title": "MOUNJARO (tirzepatide) injection — Highlights of Prescribing Information", "publisher": "FDA", "date": "2026-04-22" }, "verifiedAt": "2026-07-16" } ], "faqs": [ { "question": "Is tirzepatide FDA approved?", "answer": "Yes — tirzepatide is FDA-approved as two Eli Lilly prescription products: Mounjaro (NDA 215866), indicated as an adjunct to diet and exercise to improve glycemic control in adults and pediatric patients 10 years and older with type 2 diabetes, and Zepbound (NDA 217806), indicated with a reduced-calorie diet and increased physical activity to reduce excess body weight and maintain weight reduction long term in adults with obesity or overweight with a weight-related comorbid condition, and to treat moderate to severe obstructive sleep apnea in adults with obesity. Both were verified as active, prescription-only and not discontinued on Drugs@FDA on 2026-07-16. The approval attaches to those two applications, not to the molecule — tirzepatide sold by anyone other than the holder of an approved application is not an approved drug, and no approval covers anti-aging, body recomposition or general non-obese weight loss.", "source": { "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2026/215866s009lbl.pdf", "title": "MOUNJARO (tirzepatide) injection — Highlights of Prescribing Information", "publisher": "FDA", "date": "2026-04-22" }, "verifiedAt": "2026-07-16" }, { "question": "Is it legal to buy tirzepatide from a peptide website?", "answer": "No. FDA told USApeptide.com on 2025-02-26 that although 'there are FDA-approved tirzepatide products on the market in the U.S., there are no approved drug applications pursuant to section 505 of the FD&C Act in effect for' the tirzepatide it was selling, making those products unapproved new drugs whose introduction into interstate commerce violates sections 301(d) and 505(a). FDA also found them misbranded under section 502(f)(1): approved tirzepatide is available only by prescription, and 'because the aforementioned drugs are prescription drugs intended for conditions that are not amenable to self-diagnosis and treatment by a layperson, adequate directions cannot be written such that a layperson can use the products safely for their intended use.' The 'research use only' and 'not for human consumption' labels do not change this result — FDA held that despite those statements, 'evidence obtained from your website establishes that certain products offered for sale … are drugs intended for human use', and the sentences it cited as that evidence were the site's own accurate descriptions of what the APPROVED drug does.", "source": { "url": "https://www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/warning-letters/usapeptidecom-696885-02262025", "title": "Warning Letter — USApeptide.com (696885)", "publisher": "FDA", "date": "2025-02-26", "quote": "Despite statements on your product labeling and website such as \"research use only,\" \"not for human consumption,\" \"lab purposes only,\" and \"not intended to diagnose, cure, mitigate, treat or prevent disease,\" evidence obtained from your website establishes that certain products offered for sale by www.usapeptide.com are drugs intended for human use." }, "verifiedAt": "2026-07-16" }, { "question": "Can I still get compounded tirzepatide in 2026?", "answer": "FDA proposed on 2026-05-01 not to add tirzepatide to the 503B Bulks List, which is the list of bulk substances outsourcing facilities may compound from, and its stated reason was that the approved drug is adequate: FDA 'tentatively finds no basis to conclude that there is an attribute of the FDA-approved drug products containing tirzepatide that makes them medically unsuitable to treat certain patients for a condition that FDA has identified for evaluation.' The shortage rationale that supported the 2023-2024 compounded-tirzepatide market is gone — FDA recorded that 'as of the date of this notice, FDA-approved tirzepatide drug products are not on the FDA drug shortage list', and said it 'does not interpret such issues, such as shortages and backorders, to be within the meaning of clinical need'. The proposal is not final: comments were due 2026-06-30. Eli Lilly filed a comment opposing the nomination (FDA-2015-N-3469-0404, 2024-11-04).", "source": { "url": "https://www.govinfo.gov/content/pkg/FR-2026-05-01/html/2026-08552.htm", "title": "List of Bulk Drug Substances for Which There Is a Clinical Need Under Section 503B of the Federal Food, Drug, and Cosmetic Act (Docket No. FDA-2018-N-3240)", "publisher": "Federal Register / FDA", "date": "2026-05-01", "quote": "This notice identifies three bulk drug substances that FDA has considered and proposes not to include on the 503B Bulks List: semaglutide, tirzepatide, and liraglutide." }, "verifiedAt": "2026-07-16" }, { "question": "Is oral or sublingual tirzepatide legit?", "answer": "No tirzepatide drug product is FDA-approved in the oral, sublingual or buccal routes — FDA stated exactly that on 2026-05-01 while refusing to find a clinical need for compounded versions of them, rejecting the nominators' arguments that injections cause 'patient discomfort', require refrigerated storage and 'may lead to adherence failure'. FDA's answer was that 'the statutory standard for inclusion of a substance on the 503B Bulks List is clinical need--not \"preference\"', and that 'the potential for a patient to experience \"discomfort\" after receiving an injection does not mean that injectable product is medically unsuitable for the patient.' Every approved tirzepatide product — Mounjaro and Zepbound, in pens and in vials — is a solution for subcutaneous injection.", "source": { "url": "https://www.govinfo.gov/content/pkg/FR-2026-05-01/html/2026-08552.htm", "title": "List of Bulk Drug Substances for Which There Is a Clinical Need Under Section 503B of the Federal Food, Drug, and Cosmetic Act (Docket No. FDA-2018-N-3240)", "publisher": "Federal Register / FDA", "date": "2026-05-01", "quote": "We address here the proposals for oral, ``oral sublingual,'' and buccal products because no tirzepatide drug product is approved in these routes of administration." }, "verifiedAt": "2026-07-16" }, { "question": "Is research-grade tirzepatide the same as Mounjaro?", "answer": "Not established, and FDA's inspection of one supplier is the reason to doubt it. FDA inspected Harbin Jixianglong Biotech Co., Ltd., a Chinese manufacturer of tirzepatide API shipped to the United States, in November 2025 and issued a warning letter on 2026-05-01 concluding that its APIs are adulterated under section 501(a)(2)(B) because its methods, facilities or controls do not conform to CGMP. FDA recorded that the firm shipped lots of tirzepatide API to the U.S. market in 2024 without completing analytical method validation for assay, related substances, high molecular weight aggregates and amino acid ratio, and in 2025 without completing method verification for the bacterial endotoxin test — the tests that establish, respectively, how much tirzepatide is there, what else is there, whether it is the right peptide, and whether it is safe to inject. The firm told FDA its tirzepatide API was 'in the development stage and full validation of all analytical methods has yet to be completed.' This is one supplier on one inspection and does not describe every vial on the market; it does mean that a 'research grade' label is a statement about intended use, not a measurement of identity or purity.", "source": { "url": "https://www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/warning-letters/harbin-jixianglong-biotech-co-ltd-723330-05012026", "title": "Warning Letter 320-26-73 — Harbin Jixianglong Biotech Co., Ltd. (723330)", "publisher": "FDA", "date": "2026-05-01", "quote": "Because your methods, facilities, or controls for manufacturing, processing, packing, or holding do not conform to CGMP, your APIs are adulterated within the meaning of section 501(a)(2)(B) of the Federal Food, Drug, and Cosmetic Act (FD&C Act), 21 U.S.C. 351(a)(2)(B)." }, "verifiedAt": "2026-07-16" } ] }, { "slug": "vip", "name": "VIP", "aliases": [ "Vasoactive Intestinal Peptide", "Vasoactive Intestinal Polypeptide", "Aviptadil", "Aviptadil acetate", "ZYESAMI", "RLF-100", "VIP nasal spray" ], "url": "https://peptides101.com/compounds/vip", "moleculeNote": "A 28-amino-acid peptide — FDA's own description in the 2019 proposed rule is 'VIP, a 28-amino acid peptide'. Three disambiguations matter on this record, and all three are routinely collapsed. (1) VIP AND AVIPTADIL ARE THE SAME MOLECULE UNDER TWO NAMES. Aviptadil is the INN for synthetic VIP; FDA's Substance Registration System lists 'VIP' and 'HUMAN VIP' among the synonyms of AVIPTADIL under UNII A67JUW790C. A reader searching 'VIP' finds compounded nasal sprays and a reader searching 'aviptadil' finds a failed NIH phase 3 trial, and they are looking at one substance. That UNII record carries its own caution, verbatim: 'UNII availability does not imply any regulatory review or approval.' (2) VIP IS ENDOGENOUS. It is made in the human body, so the literature is dominated by studies MEASURING circulating VIP as a marker of disease rather than administering it. That is the exact trap that reduces MOTS-c from an apparent four human RCTs to zero, and it applies here with full force — see the evidence note, where the administration check is recorded study by study rather than assumed. (3) PEMZIVIPTADIL (PB1046) IS NOT VIP. It is a long-acting VIP ANALOGUE fused to an elastin-like polypeptide, developed by PhaseBio; both of its registered phase 2 studies (NCT03556020, NCT04433546) are TERMINATED. Analogue data does not transfer to VIP, in either direction.", "quickAnswer": "VIP (vasoactive intestinal peptide, also called aviptadil) is not the active ingredient of any FDA-approved drug — a Drugs@FDA search returns no application under either name — but its compounding position differs from most peptides sold in this market: FDA lists Vasoactive Intestinal Peptide in Category 1 of its 503A bulk drug substances document updated 14 May 2026, and states it 'does not intend to take action against a compounder for compounding drugs using bulk drug substances listed in category 1, provided that the conditions described in the guidance document are met.' That is conditional enforcement discretion during an evaluation, not inclusion on the 503A bulks list and not an approval: in a proposed rule of 5 September 2019 FDA proposed that VIP NOT be placed on that list, finding that 'the physiochemical characteristics, safety, effectiveness, and historical use of VIP weigh against inclusion', and that rule has not been finalised. On the use VIP is sold for, FDA reported it located only one published study of VIP in a condition related to 'chronic inflammatory response syndrome', 'which failed to clearly establish benefits of the administration of VIP.' VIP has been administered to humans in one large randomised trial under its other name: in the NIAID-sponsored phase 3 TESICO trial, intravenous aviptadil 'did not significantly improve clinical outcomes up to day 90 when compared with placebo' in COVID-19-associated acute hypoxaemic respiratory failure.", "fdaStatus": { "value": "not-approved", "note": "No drug product containing VIP or aviptadil holds an FDA application. Six Drugs@FDA queries across two field paths and both names returned NOT_FOUND on 2026-08-02, with a control query on the same field returning results — the queries are recorded in this file's header comment so the negative can be re-run rather than trusted. The openFDA `drug/label` and `other/nsde` endpoints likewise return NOT_FOUND for aviptadil: there is no marketed-product listing and no prescribing information. WHY 'not-approved' AND NOT 'investigational', because this is the close call on this record. The vocabulary reserves 'investigational' for ACTIVE development by an identifiable sponsor with registered trials. ClinicalTrials.gov returns nine studies for the term 'aviptadil' and not one is recruiting or enrolling: they are COMPLETED, TERMINATED, WITHDRAWN, NO_LONGER_AVAILABLE, or — in the case of the I-SPY COVID-19 platform trial (NCT04488081) — an ACTIVE_NOT_RECRUITING platform on which aviptadil was one of fourteen historical arms. The most recently registered aviptadil trial, a phase 3 of the inhaled product, was WITHDRAWN with an actual enrolment of zero. The original US sponsor is out: NRx Pharmaceuticals' Form 10-K for 2025 states that in December 2022 it transferred all ZYESAMI manufacturing rights and know-how to Relief Therapeutics. A corporate pipeline page is not a registered trial, and 'still in development' with no trial open is the claim this vocabulary was written to refuse. SCOPE: this field is a statement about FDA and the United States only. This record makes no claim, in either direction, about whether any national regulator outside the US has authorised a product containing aviptadil — that was not verified against a regulator's own document and is therefore left blank rather than guessed.", "source": { "url": "https://api.fda.gov/drug/drugsfda.json?search=products.active_ingredients.name:%22AVIPTADIL%22&limit=5", "title": "Drugs@FDA — openFDA drug/drugsfda query for AVIPTADIL (no matching applications)", "publisher": "FDA", "date": "2026-07-31", "quote": "{\"error\":{\"code\":\"NOT_FOUND\",\"message\":\"No matches found!\"}}" }, "verifiedAt": "2026-08-02" }, "compoundingStatus": { "value": "category-1", "note": "Verified by downloading fda.gov/media/94155/download with a browser user-agent and extracting the text locally on 2026-08-02: 'Vasoactive Intestinal Peptide' is the final bullet in '503A Category 1 – Bulk Drug Substances Under Evaluation' in the list updated 14 May 2026. It is not in Category 2, which contains exactly six substances (Cesium Chloride, Domperidone, Germanium Sesquioxide, Ibutamoren Mesylate, Kisspeptin-10, and Quinacrine Hydrochloride for intrauterine administration), and not in Category 3. READ THE CATEGORY PRECISELY, because it is about to be sold as something it is not. Category 1 is not the 503A bulks list. VIP is NOT on the 503A bulks list; the list is codified at 21 CFR 216.23(a) and Category 1 is an interim holding pen for substances still being evaluated. What Category 1 buys is enforcement discretion under a guidance, conditional on four circumstances all being present, and FDA states it lasts only 'until the agency decides on inclusion of these substances on the 503A bulks list.' FDA has already said in a proposed rule what it intends to decide — that VIP should not be included. Being under evaluation is not an approval, an endorsement, or a safety finding, and this is the one compound on this site where that sentence does the most work.", "source": { "url": "https://www.fda.gov/media/94155/download", "title": "Bulk Drug Substances Nominated for Use in Compounding Under Section 503A of the Federal Food, Drug, and Cosmetic Act", "publisher": "FDA", "date": "2026-05-14", "quote": "Vasoactive Intestinal Peptide" }, "verifiedAt": "2026-08-02" }, "evidence": { "tier": "promising-but-unproven", "humanAdministrationChecked": true, "note": "The tier reads more generously than this record supports, so read the note rather than the badge. 'Promising-but-unproven' is assigned only because human ADMINISTRATION data exists at scale — the vocabulary reserves this tier for programmes with a human signal that were tested and not established, explicitly including ones that failed. This is one that failed, and was stopped for futility by its own monitoring board. ADMINISTRATION CHECK RUN, NOT ASSUMED, and it matters more here than almost anywhere on this site, because VIP is an endogenous human peptide and most of its literature measures it rather than gives it. NCT06729606 was opened through the ClinicalTrials.gov API on 2026-08-02: official title 'A Multicenter, Adaptive, Randomized, Blinded Controlled Trial of the Safety and Efficacy of Investigational Therapeutics for Hospitalized Patients With Acute Respiratory Distress Syndrome Associated With COVID-19 (Trial H1: Aviptadil)'; lead sponsor National Institute of Allergy and Infectious Diseases (NIAID); phase 3; allocation RANDOMIZED, parallel, TRIPLE-masked (participant, care provider, investigator); arms 'Aviptadil + SOC' (experimental) and 'Placebo + SOC' (placebo comparator); interventions typed BIOLOGICAL 'Aviptadil', administered by intravenous infusion, and BIOLOGICAL 'Aviptadil Placebo', described as commercially available 0.9% sodium chloride solution; enrolment 471 ACTUAL; status COMPLETED (start 2021-04-20 ACTUAL, primary completion 2022-08-22 ACTUAL, completion 2022-11-20 ACTUAL); results first posted 2025-10-09; hasResults true. VIP was given to people. It was not measured as a biomarker. WHAT THE TRIAL FOUND. Per the published report, 473 participants were enrolled and 471 randomly assigned in the aviptadil comparison, with a modified intention-to-treat population of 461 (231 aviptadil, 230 matched placebo). The odds ratio for being in a better category of the primary ordinal endpoint at day 90 was 1.11 (95% CI 0.80-1.55; p=0.54). Up to day 90, 86 participants in the aviptadil group and 83 in the placebo group died; the cumulative percentage was 38% versus 36% (hazard ratio 1.04, 95% CI 0.77-1.41; p=0.78). The report states: 'The independent data and safety monitoring board recommended stopping the aviptadil trial on May 25, 2022, for futility.' SCOPE, WHICH IS THE WHOLE POINT. This evidence is intravenous aviptadil in critically ill adults with COVID-19-associated hypoxaemic respiratory failure. It says nothing about the product VIP is actually sold as — a compounded intranasal spray for 'chronic inflammatory response syndrome'. On that use FDA reported it located exactly one published study, which it said failed to clearly establish benefits. A large negative trial by one route in one population is not evidence for a different route in a different population, in either direction.", "source": { "url": "https://pubmed.ncbi.nlm.nih.gov/37348524/", "title": "Intravenous aviptadil and remdesivir for treatment of COVID-19-associated hypoxaemic respiratory failure in the USA (TESICO): a randomised, placebo-controlled trial — Lancet Respiratory Medicine 2023;11(9):791-803", "publisher": "PubMed", "date": "2023-06-19", "quote": "Among patients with COVID-19-associated acute hypoxaemic respiratory failure, aviptadil did not significantly improve clinical outcomes up to day 90 when compared with placebo." }, "verifiedAt": "2026-08-02" }, "fdaApproval": null, "fdaFindings": [ { "finding": "FDA proposed not to place VIP on the 503A bulks list, finding that its physiochemical characteristics, safety, effectiveness and historical use weigh against inclusion. The Pharmacy Compounding Advisory Committee voted the same way at its meeting on 3 November 2016.", "note": "A PROPOSED rule, and after seven years still only proposed — which is why VIP is simultaneously a substance FDA has said it intends to exclude and a substance compounders may use under enforcement discretion. Both halves are true at once, and sites quoting either half alone get VIP wrong in opposite directions. Verified as still-not-final two ways on 2026-08-02: a Federal Register API search for documents of type RULE from FDA mentioning 'bulk drug substances' and '503A' published on or after 2019-09-06 returns a count of zero; and FDA's own bulks page, current as of 2026-05-14, still states of this proposal 'After considering public comments, the agency will issue a final regulation.' Worth setting beside the July 2026 PCAC story on this site: there the committee voted AGAINST FDA staff on six of seven peptides. Here the committee voted WITH staff, in 2016, and a decade later nothing has been codified either way. A committee vote in either direction is not a rule.", "source": { "url": "https://www.federalregister.gov/documents/2019/09/05/2019-18951/amendments-to-the-list-of-bulk-drug-substances-that-can-be-used-to-compound-drug-products-in", "title": "Amendments to the List of Bulk Drug Substances That Can Be Used to Compound Drug Products in Accordance With Section 503A of the Federal Food, Drug, and Cosmetic Act (proposed rule, 84 FR 46688)", "publisher": "FDA", "date": "2019-09-05", "quote": "On balance, the physiochemical characteristics, safety, effectiveness, and historical use of VIP weigh against inclusion of this substance on the 503A Bulks List. FDA proposed to the PCAC that this substance not be included on the 503A Bulks List. At its meeting on November 3, 2016, the PCAC voted not to include VIP on the list. … The proposed rule would not place VIP on the 503A Bulks List." }, "verifiedAt": "2026-08-02" }, { "finding": "FDA is not taking action against compounders for using Category 1 substances. FDA states that substances in Category 1 may be eligible for inclusion on the 503A bulks list, were nominated with sufficient supporting information for FDA to evaluate them, and do not appear on any other list, and that FDA does not intend to take action against a compounder for compounding drugs using them provided the conditions in the guidance document are met.", "note": "This is the finding that genuinely separates VIP from every peptide this site was built to cover, and it is the one most likely to be quoted without its second half. 'Does not intend to take action' is a statement of enforcement intent in a nonbinding guidance. It is not approval, it is not a determination that the substance is safe or effective, and it does not make a compounded VIP product an approved drug. FDA attaches an explicit end date to it on the same page: substances in category 1 'may continue to be within the scope of the interim enforcement policy described in FDA's guidance until the agency decides on inclusion of these substances on the 503A bulks list or unless the agency removes the substances from category 1 based on, for example, information about safety risks.' FDA has already published what it proposes to decide.", "source": { "url": "https://www.fda.gov/drugs/human-drug-compounding/bulk-drug-substances-used-compounding-under-section-503a-fdc-act", "title": "Bulk Drug Substances Used in Compounding Under Section 503A of the FD&C Act", "publisher": "FDA", "date": "2026-05-14", "quote": "Category 1 – These substances may be eligible for inclusion on the 503A bulks list, were nominated with sufficient supporting information for FDA to evaluate them, and do not appear on any other list. FDA does not intend to take action against a compounder for compounding drugs using bulk drug substances listed in category 1, provided that the conditions described in the guidance document are met." }, "verifiedAt": "2026-08-02" }, { "finding": "The enforcement policy is conditional on all four of FDA's stated circumstances being present: the substance appears in 503A Category 1; the original and all subsequent manufacturers of the bulk drug substance are registered under section 510; the substance is accompanied by a valid certificate of analysis; and the compounded drug product complies with all other conditions of section 503A.", "note": "Recorded in full because the conditions are where the discretion actually lives, and because they are load-bearing for a consumer. The policy attaches to compounding by a state-licensed pharmacy, a federal facility or a licensed physician — not to a vial bought from a research-chemical site, which satisfies none of these circumstances. Note condition (2): every manufacturer in the chain must be FDA-registered under section 510, which is a fact about a supply chain the purchaser cannot see. FDA also states in this guidance that products compounded from substances nominated on or after the guidance's publication date of 7 January 2025 are outside the policy entirely. The guidance is headed, on every page, 'Contains Nonbinding Recommendations'.", "source": { "url": "https://www.fda.gov/media/174456/download", "title": "Interim Policy on Compounding Using Bulk Drug Substances Under Section 503A of the Federal Food, Drug, and Cosmetic Act — Guidance for Industry", "publisher": "FDA", "date": "2025-01-07", "quote": "However, at this time, until a substance has been evaluated and is identified in a final rule as being included or not included on the 503A bulks list, FDA does not intend to take action against a State-licensed pharmacy, Federal facility, or licensed physician compounding a drug product using a bulk drug substance that is not a component of an FDA-approved drug product, the subject of an applicable USP or NF monograph, or on the 503A bulks list codified at 21 CFR 216.23(a), if all of the following circumstances are present: (1) The bulk drug substance appears in 503A Category 1 on FDA's website …; (2) The original manufacturer and all subsequent manufacturers of the bulk drug substance are establishments that are registered under section 510 …; (3) The bulk drug substance is accompanied by a valid COA; and (4) The drug product compounded using the bulk drug substance is compounded in compliance with all other conditions of section 503A of the FD&C Act." }, "verifiedAt": "2026-08-02" }, { "finding": "On effectiveness, FDA reported that it located only one published study of VIP in a condition that appears to be related to 'chronic inflammatory response syndrome' (CIRS), and that the study failed to clearly establish benefits of the administration of VIP.", "note": "Directly on point for the use VIP is actually sold for, which no other finding on this record reaches. The single study FDA located is listed in the proposed rule's reference list as Shoemaker, R.C., et al., 'Vasoactive Intestinal Polypeptide (VIP) Corrects Chronic Inflammatory Response Syndrome (CIRS) Acquired Following Exposure to Water-Damaged Buildings', Health, 5:396-401, 2013. FDA also recorded, in its own footnote, what it could establish about the condition itself: 'CIRS is a term we located in three publications. It appears to be the subject of research. It is not listed in the International Statistical Classification of Diseases and Related Health Problems (ICD-10), a medical classification list by the World Health Organization. Further, CIRS is not listed in the Medical Dictionary for Regulatory Activities (MedDRA).' Read that as what it is — a finding about the classification status of a term, not a verdict on whether patients are unwell.", "source": { "url": "https://www.federalregister.gov/documents/2019/09/05/2019-18951/amendments-to-the-list-of-bulk-drug-substances-that-can-be-used-to-compound-drug-products-in", "title": "Amendments to the List of Bulk Drug Substances That Can Be Used to Compound Drug Products in Accordance With Section 503A of the Federal Food, Drug, and Cosmetic Act (proposed rule, 84 FR 46688)", "publisher": "FDA", "date": "2019-09-05", "quote": "Regarding effectiveness, we located only one published study of VIP in a condition that appears to be related to CIRS, which failed to clearly establish benefits of the administration of VIP." }, "verifiedAt": "2026-08-02" }, { "finding": "FDA stated that VIP is well characterized physically and chemically, but that absent sufficient controls on its production, synthesis is likely to result in peptides of different lengths or different amino acid sequencing.", "note": "A more interesting finding than it looks, and it cuts against a defence the market makes on VIP's behalf. Unlike BPC-157, which FDA considers not well-characterized, VIP the molecule is well-characterized — FDA says so. The concern is not the molecule, it is the MANUFACTURE: without controls on synthesis, what comes out is likely to be peptides of the wrong length or the wrong sequence. That is a risk carried entirely by the supplier, and it is the reason condition (2) of the enforcement policy is about section 510 registration of every manufacturer in the chain rather than about the peptide.", "source": { "url": "https://www.federalregister.gov/documents/2019/09/05/2019-18951/amendments-to-the-list-of-bulk-drug-substances-that-can-be-used-to-compound-drug-products-in", "title": "Amendments to the List of Bulk Drug Substances That Can Be Used to Compound Drug Products in Accordance With Section 503A of the Federal Food, Drug, and Cosmetic Act (proposed rule, 84 FR 46688)", "publisher": "FDA", "date": "2019-09-05", "quote": "VIP is well characterized physically and chemically, but absent sufficient controls on its production, synthesis is likely to result in peptides of different lengths or different amino acid sequencing." }, "verifiedAt": "2026-08-02" }, { "finding": "FDA stated it did not find sufficient information to determine the historical use of VIP in compounded drug products, while noting that it appears VIP is currently used in compounded nasal sprays.", "note": "Historical use in compounding is one of the four statutory criteria FDA weighs for the 503A bulks list, and on VIP it produced a blank rather than a positive. FDA is recording both halves at once: it could not document a history of use, and it could see the product being sold. The 'long history of compounding' framing used in VIP marketing is therefore not something FDA found — it is something FDA looked for and did not find.", "source": { "url": "https://www.federalregister.gov/documents/2019/09/05/2019-18951/amendments-to-the-list-of-bulk-drug-substances-that-can-be-used-to-compound-drug-products-in", "title": "Amendments to the List of Bulk Drug Substances That Can Be Used to Compound Drug Products in Accordance With Section 503A of the Federal Food, Drug, and Cosmetic Act (proposed rule, 84 FR 46688)", "publisher": "FDA", "date": "2019-09-05", "quote": "We did not find sufficient information to determine the historical use of VIP in compounded drug products. However, it appears that VIP is currently used in compounded nasal sprays." }, "verifiedAt": "2026-08-02" } ], "safetySignals": [ { "signal": "FDA stated that although most adverse reactions observed related to the use of VIP appear to be relatively mild, VIP has been associated with severe immunologic reactions.", "note": "The whole sentence, both clauses, because each half is quoted alone by a different audience. FDA is not describing VIP as broadly dangerous, and it is not describing it as benign. This sits alongside FDA's synthesis finding above: a peptide that may be produced with the wrong length or sequence, given by a mucosal route, is the standard setup for an immunologic reaction, and no immunogenicity study of a compounded VIP product is identified anywhere in the proposed rule.", "source": { "url": "https://www.federalregister.gov/documents/2019/09/05/2019-18951/amendments-to-the-list-of-bulk-drug-substances-that-can-be-used-to-compound-drug-products-in", "title": "Amendments to the List of Bulk Drug Substances That Can Be Used to Compound Drug Products in Accordance With Section 503A of the Federal Food, Drug, and Cosmetic Act (proposed rule, 84 FR 46688)", "publisher": "FDA", "date": "2019-09-05", "quote": "Although most adverse reactions observed related to the use of VIP appear to be relatively mild, it has been associated with severe immunologic reactions." }, "verifiedAt": "2026-08-02" }, { "signal": "In the TESICO trial, the primary safety outcome — death, serious adverse events, organ failure, serious infection, or grade 3 or 4 adverse events up to day 5 — occurred in 146 (63%) of 231 patients in the aviptadil group compared with 129 (56%) of 230 participants in the placebo group, an odds ratio of 1.40 (95% CI 0.94-2.08; p=0.10).", "note": "Read this as the trial reported it and not as a headline in either direction. The confidence interval crosses 1, so the difference is not statistically significant; the point estimate is nonetheless numerically higher in the aviptadil group, and the trial was stopped for futility rather than for harm. The population is the other constraint: 94% of participants were in an intensive care unit at baseline and roughly two in five were on invasive mechanical ventilation, so these event rates describe critical illness, not a tolerability profile that transfers to anyone else. What the trial does establish is that a safety database of this size and quality exists for intravenous aviptadil in this population and for no other use of VIP.", "source": { "url": "https://pubmed.ncbi.nlm.nih.gov/37348524/", "title": "Intravenous aviptadil and remdesivir for treatment of COVID-19-associated hypoxaemic respiratory failure in the USA (TESICO): a randomised, placebo-controlled trial — Lancet Respiratory Medicine 2023;11(9):791-803", "publisher": "PubMed", "date": "2023-06-19", "quote": "The primary safety outcome of death, serious adverse events, organ failure, serious infection, or grade 3 or 4 adverse events up to day 5 occurred in 146 (63%) of 231 patients in the aviptadil group compared with 129 (56%) of 230 participants in the placebo group (OR 1·40, 95% CI 0·94-2·08; p=0·10)." }, "verifiedAt": "2026-08-02" } ], "faqs": [ { "question": "Is VIP FDA-approved?", "answer": "No. No drug product containing vasoactive intestinal peptide — or aviptadil, the same molecule under its International Nonproprietary Name — holds an FDA application. Queried on 2 August 2026, FDA's Drugs@FDA database returns 'No matches found' for both names, across both the generic-name field and the active-ingredient field, and for truncated wildcard forms of both. The same field queried for a control substance returns results, so the empty answer is a fact about the database rather than an artifact of the query — a distinction that matters, because a badly-scoped search of this same database produced a false 'not in Drugs@FDA' claim about a different peptide. FDA's product-labeling and marketed-product endpoints likewise return no aviptadil record, meaning there is no FDA-approved prescribing information for it and therefore no approved indication, no approved route and no approved population.", "source": { "url": "https://api.fda.gov/drug/drugsfda.json?search=products.active_ingredients.name:%22AVIPTADIL%22&limit=5", "title": "Drugs@FDA — openFDA drug/drugsfda query for AVIPTADIL (no matching applications)", "publisher": "FDA", "date": "2026-07-31", "quote": "{\"error\":{\"code\":\"NOT_FOUND\",\"message\":\"No matches found!\"}}" }, "verifiedAt": "2026-08-02" }, { "question": "Can a compounding pharmacy legally make VIP nasal spray in 2026?", "answer": "VIP is not on FDA's 503A bulks list, but it sits in Category 1 of FDA's interim policy, and FDA has stated it does not intend to take action against a compounder using a Category 1 substance if four circumstances are ALL present. FDA's words: it does not intend to take action against 'a State-licensed pharmacy, Federal facility, or licensed physician' where (1) the bulk drug substance appears in 503A Category 1 on FDA's website; (2) the original manufacturer and all subsequent manufacturers of the substance are registered under section 510; (3) the substance is accompanied by a valid certificate of analysis; and (4) the compounded product complies with all other conditions of section 503A. Three things follow that the marketing tends to drop. This is enforcement discretion in a guidance headed 'Contains Nonbinding Recommendations', not a finding that VIP is safe or effective and not an approval. It is temporary by its own terms — FDA says it runs 'until a substance has been evaluated and is identified in a final rule as being included or not included on the 503A bulks list', and FDA has already proposed a rule that would exclude VIP. And it reaches only compounding by a licensed pharmacy, federal facility or physician; a vial bought from a research-chemical seller satisfies none of the four circumstances.", "source": { "url": "https://www.fda.gov/media/174456/download", "title": "Interim Policy on Compounding Using Bulk Drug Substances Under Section 503A of the Federal Food, Drug, and Cosmetic Act — Guidance for Industry", "publisher": "FDA", "date": "2025-01-07", "quote": "However, at this time, until a substance has been evaluated and is identified in a final rule as being included or not included on the 503A bulks list, FDA does not intend to take action against a State-licensed pharmacy, Federal facility, or licensed physician compounding a drug product using a bulk drug substance … if all of the following circumstances are present: (1) The bulk drug substance appears in 503A Category 1 on FDA's website …; (2) The original manufacturer and all subsequent manufacturers of the bulk drug substance are establishments that are registered under section 510 …; (3) The bulk drug substance is accompanied by a valid COA; and (4) The drug product compounded using the bulk drug substance is compounded in compliance with all other conditions of section 503A of the FD&C Act." }, "verifiedAt": "2026-08-02" }, { "question": "Is there evidence that VIP nasal spray works for CIRS or mold illness?", "answer": "Not on the record FDA compiled. In its proposed rule of 5 September 2019, FDA evaluated VIP specifically for 'a condition described as \"chronic inflammatory response syndrome\" (CIRS)' and reported: 'Regarding effectiveness, we located only one published study of VIP in a condition that appears to be related to CIRS, which failed to clearly establish benefits of the administration of VIP.' The study FDA located is listed in the rule's references as Shoemaker et al., Health, 5:396-401, 2013. FDA separately recorded what it could establish about the term itself: 'CIRS is a term we located in three publications. It appears to be the subject of research. It is not listed in the International Statistical Classification of Diseases and Related Health Problems (ICD-10) … Further, CIRS is not listed in the Medical Dictionary for Regulatory Activities (MedDRA).' Two cautions on reading that. It is a finding about how a term is classified, not a statement that the patients are well. And FDA's own conclusion was a conclusion about a compounding list, not about any individual: on balance, it wrote, the physiochemical characteristics, safety, effectiveness and historical use of VIP 'weigh against inclusion of this substance on the 503A Bulks List.'", "source": { "url": "https://www.federalregister.gov/documents/2019/09/05/2019-18951/amendments-to-the-list-of-bulk-drug-substances-that-can-be-used-to-compound-drug-products-in", "title": "Amendments to the List of Bulk Drug Substances That Can Be Used to Compound Drug Products in Accordance With Section 503A of the Federal Food, Drug, and Cosmetic Act (proposed rule, 84 FR 46688)", "publisher": "FDA", "date": "2019-09-05", "quote": "Regarding effectiveness, we located only one published study of VIP in a condition that appears to be related to CIRS, which failed to clearly establish benefits of the administration of VIP." }, "verifiedAt": "2026-08-02" }, { "question": "Did aviptadil (Zyesami) work for COVID-19?", "answer": "No. TESICO, a randomised, placebo-controlled phase 3 trial sponsored by the US National Institute of Allergy and Infectious Diseases at 28 US sites, tested intravenous aviptadil against matched placebo in adults with COVID-19-associated acute hypoxaemic respiratory failure, and its published conclusion is that 'aviptadil did not significantly improve clinical outcomes up to day 90 when compared with placebo.' The trial randomised 471 participants in the aviptadil comparison, with 461 in the modified intention-to-treat population. The odds ratio for a better category on the primary ordinal endpoint at day 90 was 1.11 (95% CI 0.80-1.55; p=0.54). Deaths up to day 90 were 86 of 231 in the aviptadil group and 83 of 230 on placebo — 38% versus 36% (hazard ratio 1.04, 95% CI 0.77-1.41; p=0.78). The trial did not run to its planned end: 'The independent data and safety monitoring board recommended stopping the aviptadil trial on May 25, 2022, for futility.' This is the largest and most rigorous human evidence that exists for VIP by any route, and it is negative.", "source": { "url": "https://pubmed.ncbi.nlm.nih.gov/37348524/", "title": "Intravenous aviptadil and remdesivir for treatment of COVID-19-associated hypoxaemic respiratory failure in the USA (TESICO): a randomised, placebo-controlled trial — Lancet Respiratory Medicine 2023;11(9):791-803", "publisher": "PubMed", "date": "2023-06-19", "quote": "The independent data and safety monitoring board recommended stopping the aviptadil trial on May 25, 2022, for futility. … Among patients with COVID-19-associated acute hypoxaemic respiratory failure, aviptadil did not significantly improve clinical outcomes up to day 90 when compared with placebo." }, "verifiedAt": "2026-08-02" }, { "question": "Did FDA ever authorise Zyesami (aviptadil) for emergency use during COVID-19?", "answer": "No emergency use authorization for aviptadil was issued, and no aviptadil application appears in Drugs@FDA. Be careful about the sourcing here, because it is weaker than everything else on this page: FDA does not publish EUA denial letters, so there is no primary FDA document recording the decision, and the account below is the sponsor's own. NRx Pharmaceuticals told the SEC, in its annual report on Form 10-K for 2022, that a loss of contractual milestones was caused in part by 'the FDA's November decision not to approve EUA for ZYESAMI'. The company separately announced a second declined request in July 2022 and a declined Breakthrough Therapy Designation request; those two are carried only by company press releases and are not established by the filing cited here. What is independently checkable is the outcome rather than the correspondence: aviptadil holds no FDA application, has no FDA-approved labeling, and the NIH phase 3 trial that ran alongside these requests was stopped for futility.", "source": { "url": "https://www.sec.gov/Archives/edgar/data/1719406/000155837023005292/nrxp-20221231x10k.htm", "title": "NRx Pharmaceuticals, Inc. — Annual Report on Form 10-K for the year ended December 31, 2022", "publisher": "U.S. Securities and Exchange Commission (EDGAR)", "date": "2023-03-31", "quote": "The gains primarily resulted from not achieving the Earnout Cash milestones by December 31, 2022 due to changes to the anticipated re-start date of the NRX-101 Phase III clinical trial, slower enrollment in the NIH's ZYESAMI clinical trial, and the FDA's November decision not to approve EUA for ZYESAMI." }, "verifiedAt": "2026-08-02" }, { "question": "Is aviptadil still being studied in clinical trials?", "answer": "Not in any trial that is open. Searched on 2 August 2026, ClinicalTrials.gov returns nine studies for the term 'aviptadil', and none is recruiting or enrolling: they are completed, terminated, withdrawn, no-longer-available, or — for the I-SPY COVID-19 platform trial — an active-not-recruiting platform on which aviptadil was one of fourteen historical arms. The most recently registered aviptadil trial, AVICOVID-3 (NCT05137795), a phase 3 study of the inhaled product first posted on 30 November 2021, is recorded as WITHDRAWN with an actual enrolment of zero and a stated reason of 'Sponsor decision'; its registration was last updated on 14 May 2026. The original US developer has also exited: NRx Pharmaceuticals' Form 10-K for 2025 states that in December 2022 it transferred all ZYESAMI manufacturing rights and know-how to Relief Therapeutics. Corporate pipeline pages continue to list aviptadil, but a pipeline listing is not a registered trial, and there is no registered trial.", "source": { "url": "https://clinicaltrials.gov/study/NCT05137795", "title": "Inhaled ZYESAMI (Aviptadil Acetate) for the Treatment of Severe COVID-19 (AVICOVID-3) — ClinicalTrials.gov registration", "publisher": "ClinicalTrials.gov", "date": "2026-05-14", "quote": "Sponsor decision" }, "verifiedAt": "2026-08-02" } ] } ] }