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Also: MOTS c · MOTS-C · MOTs-C · MOTS3 · mitochondrial open reading frame of the 12S rRNA type-c · mitochondrial-derived peptide · MDP · the exercise mimetic · the mitochondrial peptide · MOTC · MOTSC-c · MOT-S c · MOST-c
Four separate measurements, never averaged. Independent evidence counts only studies with no sponsor attached. Methodology version v2.0-2026-10 · how we grade evidence
Not approved by any regulator, anywhere, for any indication. Claims — stated as claims — include improved insulin sensitivity and reversal of insulin resistance, weight and fat loss, improved metabolic and mitochondrial health, increased exercise capacity, bone density benefit and longevity or lifespan extension.
There are no completed human studies of MOTS-c. FDA, 2026: no clinical studies of MOTS-c in humans, no published human use of compounded or non-compounded products, and no human pharmacokinetic data. The entire efficacy base is rodents: about 20% less body-weight gain and improved insulin sensitivity in high-fat-diet mice, a roughly 50% fall in blood glucose in obese mice over three days, reduced weight gain in ovariectomised mice, reduced vascular calcification in a rat model, and bone-related effects in cell culture and mouse calvaria. The longevity claim rests on one mouse study, in which late-life intermittent dosing raised median lifespan from 912 to 970 days and maximal lifespan from 1047 to 1120 days.
One registered human trial exists — a 120-participant Phase 2a in prediabetes and overweight or obesity, recruiting from February 2026 with estimated primary completion in February 2027. It has no results and must not be cited as evidence; it was not part of FDA’s evidence review, and the registry record itself is treated as provisional here because its own intervention mapping does not match the compound and nothing independent corroborated it.
Safety is unknown rather than reassuring. FDA found no toxicology studies at all — no acute, repeat-dose, genotoxicity, reproductive, developmental or carcinogenicity work — and discounted the absence of adverse-event reports as uninformative, noting that compounders generally do not report them. It could not rule out immunogenicity with subcutaneous injection and found no clinical immunogenicity or aggregation data. It also records a string of characterisation failures: no pharmacopoeial monograph anywhere, no FDA-approved product containing it, and "MOTS-c" is a common name rather than a USAN, INN or IUPAC name, which FDA flags as an identity and dosing-error risk. One certificate of analysis reports purity with no impurity limits; another lacks testing for impurities, aggregates, bioburden, endotoxins and residual solvents; storage guidance conflicts between sources. FDA also notes that approved products already exist for both nominated indications, obesity and osteoporosis.
A concern specific to this molecule: a 16-residue peptide that is rapidly degraded in human blood into unidentified shorter fragments has no characterised metabolite safety profile.
At a glance
Proposed to act as a mitochondrial-derived signalling peptide that activates AMPK, shifting cellular metabolism toward fatty-acid oxidation and glucose uptake, with downstream effects on the folate-methionine cycle. **FDA states the molecular target is unknown**, notes the effects appear only partly AMPK-dependent, and found no dose-response assessments. There is no human pharmacokinetic data and no human study of administered MOTS-c. The closest thing to human evidence is a cell-free assay in which the peptide was incubated in human whole blood and broke down rapidly into shorter fragments; FDA observed that it is unclear whether exogenous dosing could produce active concentrations at all. Observational studies measuring endogenous MOTS-c levels in people exist but are not evidence about administering it and are not filed as such.
Dated determinations, each flagged for whether it is final and whether it covers safety only. A safety review is not an efficacy finding, and most reporting in this category conflates the two.
The narrowest margin of the six peptides recommended at the 23 to 24 July 2026 meeting. Non-binding: a proposed rule, comment period and final rule are all still required and none had issued as of 13 October 2026. The readable record for the vote is trade coverage rather than an FDA minutes document. A recommendation to permit compounding of a substance with no completed human study of any kind.
FDA, 2026: no clinical studies of MOTS-c in humans, no published human use of compounded or non-compounded products, and no human pharmacokinetic data. There is therefore no safety data of any kind, at any dose, route or duration, and no toxicology studies at all — no acute, repeat-dose, genotoxicity, reproductive, developmental or carcinogenicity work was submitted or identified. FAERS searches through March 2025 returned no reports and FDA explicitly discounts this as evidence of safety, noting that 503A compounders generally do not report adverse events, so the absence of reports is uninformative. FDA is concerned about immunogenicity with subcutaneous injection, the proposed route, citing peptide aggregation and peptide-related impurities, and says it cannot rule out these risks because no clinical immunogenicity or aggregation data exist. Characterisation failures are extensive: no USP or NF monograph, absent from the European and Japanese pharmacopoeias, in no FDA-approved drug, and "MOTS-c" is a common name and not a USAN, INN or IUPAC name, which FDA flags as creating identity and dosing-error risk. No certificate of analysis was provided in the nomination for the free base; a literature certificate reports only purity with no impurity limits and water solubility data are lacking; the acetate certificate reports identity, amino acid composition, assay, water, acetate content and purity (specification at or above 98.0%, result 99.2%) but lacks testing for impurities, aggregates, bioburden, endotoxins and residual solvents. Storage guidance conflicts between sources, and reconstitution and compounding instructions were not provided, so FDA could not evaluate solubility or product performance. FDA also notes that FDA-approved products already exist for both nominated indications, obesity and osteoporosis.
Removed with 11 other peptides in mid-April 2026; it now appears only in the "nominated but withdrawn" table on FDA’s page, content current as of 22 April 2026. It was never in Category 1, the only category covered by the interim enforcement-discretion policy.
Named alongside GW501516 and SR9009 as an AMPK activator, i.e. classified as a metabolic modulator rather than a hormone or growth factor. FDA notes it is also listed as prohibited per Global DRO.
One of the 19 substances added on 29 September 2023.
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The proposed mechanism for this ingredient has not been confirmed in humans. Marketing copy frequently states it as settled. It is not.
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