MOTS-c FDA Approval History: Regulatory Status, Safety Data, and What Clinicians Need to Know

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Is MOTS-c FDA approved?

No. MOTS-c is not an FDA-approved drug and is not a component of an FDA-approved drug [1]. FDA's July 2026 review also found no USP or National Formulary monograph, no listing in the European or Japanese pharmacopeias and no product authorized by the European Medicines Agency [1].

MOTS-c is a 16-amino-acid peptide (Met-Arg-Trp-Gln-Glu-Met-Gly-Tyr-Ile-Phe-Tyr-Pro-Arg-Lys-Leu-Arg), molecular weight about 2174.6 g/mol, encoded in mitochondrial DNA and first reported in 2015 by Lee et al. in Cell Metabolism [1][8]. MOTS-c is a common name, not an official drug name, and FDA treats the free base and the acetate salt as different bulk substances [1].

What FDA's July 2026 review found

FDA evaluated MOTS-c after a nomination to add it to the compounding bulks list for state-licensed pharmacies. Its staff searched PubMed, Embase, the Cochrane library and other sources and found no clinical study in which MOTS-c was given to humans; the 12 papers the nominator cited were not clinical studies [1].

The nominated uses were insulin resistance, obesity, osteoporosis, vascular calcification, muscle and fat metabolism, and longevity, as 5 mg and 10 mg subcutaneous injections [1]. FDA staff proposed that neither the free base nor the acetate be added to the pharmacy bulks list, for five stated reasons: the substance is not well characterized (inconsistent naming; no impurity, aggregate or endotoxin data), its use in compounding is unknown, there are no human safety or effectiveness data, there are no animal toxicity studies, and FDA-approved treatments exist for obesity and osteoporosis, two of the nominated uses [1].

Where MOTS-c sits in FDA's compounding lists

FDA's page on bulk substances that may raise significant safety risks lists MOTS-c in the nominated-but-withdrawn table, which holds substances previously in category 2 whose nominators withdrew them [6]. That entry is not an approval and not a listing, and removal from category 2 was not a finding that the substance is safe [6]. FDA's stated concerns are that important safety information is missing and that injectable peptides may pose an immunogenicity risk because of aggregation and impurities [6].

MOTS-c appears in none of the three categories on FDA's list for state-licensed pharmacies and physicians (updated May 14, 2026) or on FDA's list for outsourcing facilities (updated March 21, 2025) [2][3][9]. The category 1 policy, under which FDA generally does not intend to act against a compounder that meets the conditions, does not cover it [9].

Under the federal compounding statute, a state-licensed pharmacy or physician may compound with a bulk substance only if it complies with an applicable USP or NF monograph, is a component of an FDA-approved drug, or appears on FDA's bulks list [9]. MOTS-c meets none of those three conditions, and no outsourcing facility reported compounding it between January 2017 and December 2025 [1][9].

The July 2026 advisory committee vote and the October 2026 HHS draft

FDA's Pharmacy Compounding Advisory Committee reviewed MOTS-c on July 23, 2026 and voted in favor of adding it to the bulks list, against FDA staff's recommendation [4][5]. Advisory committee recommendations are non-binding [4]. Adding a substance to the bulks list takes notice-and-comment rulemaking, and MOTS-c is not on the list [9][4].

HHS filed a draft enforcement-discretion policy for compounding with certain peptides on October 28, 2026 (Federal Register document 2026-22192, publication scheduled for October 30, 2026, comments due two weeks after publication) [5][10]. It names MOTS-c among six peptides, with BPC-157, epitalon, KPV, Semax and TB-500, and covers MOTS-c acetate given by subcutaneous or intramuscular injection [5][10]. HHS says it does not intend to take enforcement action against a state-licensed pharmacy, federal facility or licensed physician compounding with it if the policy's conditions are met, such as a single active ingredient, a patient-specific prescription, an FDA-registered manufacturer with a certificate of analysis, and a label reading This is a compounded drug product. Not for resale. [5][10]

The draft is not an approval and does not put MOTS-c on any list. The notice says it does not establish any rights for any person and is not binding on HHS or the public, and HHS may revisit it, for example if a safety signal or a product quality issue arises [5]. Compounded drugs are not FDA-approved: FDA does not review their safety, effectiveness or quality before marketing [5].

What safety data exist for MOTS-c

Searches of FDA's adverse-event database through March 9, 2025 retrieved no MOTS-c reports [1]. That is not evidence of safety: FDA found no human exposure data by any route and no animal toxicity studies, so safety in humans is unknown [1].

For injections, the agency's stated concern is immunogenicity, an immune reaction, from aggregation and peptide-related impurities; MOTS-c has 16 amino acids and there are no immunogenicity data [1].

All of the pharmacology comes from cells and rodents [1][8]. In mice, injected MOTS-c reduced weight gain on a high-fat diet (about 20% lower body weight after 8 weeks at 0.5 mg/kg/day intraperitoneal) and prevented age-dependent and high-fat-diet-induced insulin resistance, with skeletal muscle as the main target organ and AMPK activation as the cellular effect [8][1]. One study found that a late-life schedule of 15 mg/kg three times weekly from 23.5 months of age lengthened median lifespan in mice from 912 to 970 days [11][1]. FDA notes that the molecular targets are unknown and that no dose-response relationships were assessed [1].

FDA also cited an in-vitro study in which MOTS-c is quickly broken down in human blood, which raises the question of whether injecting it can produce active levels in people [1].

Pharmacokinetics and what dose is approved

The only kinetic observation is that MOTS-c breaks down rapidly in human blood in vitro; FDA found no pharmacokinetic data from humans or live animals [1]. There is no approved dose [1]. The nominated products were 5 mg and 10 mg subcutaneous injections, and the rodent doses of 0.5 to 15 mg/kg cannot be converted into human doses [1].

Human studies measured the body's own MOTS-c, not injections

Reynolds et al. (Nature Communications, 2021) found that exercise induces endogenous MOTS-c expression in skeletal muscle and in the circulation in humans; participants were not given the peptide [11].

von Walden et al. (Journal of Applied Physiology, 2021) randomized 30 healthy adults to endurance exercise (n=10), resistance exercise (n=10) or control (n=10) [12]. Humanin rose after endurance exercise, while MOTS-c showed only a trend to increase, and plasma MOTS-c was not related to fitness [12].

Is MOTS-c prohibited in sport?

Yes. WADA's Prohibited List names MOTS-c in S4.4.1, the metabolic modulator section covering activators of AMP-activated protein kinase [7]. It is prohibited at all times, in and out of competition, and S4.4 substances are non-Specified Substances [7]. MOTS-c is on the 2026 List, in force since January 1, 2026, and remains on the 2027 List in the tracked-changes version dated 26 August 2026 [7][13].

How MOTS-c is marketed

FDA describes the market as websites selling MOTS-c alone and in combinations, including an IV cocktail offered by a wellness clinic, for metabolism, weight loss, glucose control, performance and anti-aging [1]. The research on AMPK signaling and folate metabolism behind those claims comes from cells and mice [1][8].