MOTS-c and the FDA 503A Decision: The Mitochondrial Peptide FDA Declined to List

The Short Answer

At the July 23, 2026 PCAC meeting, FDA proposed that MOTS-c (free base) and MOTS-c acetate not be added to the 503A Bulks List. The nomination (later withdrawn, with FDA proceeding) sought MOTS-c by the injectable route for metabolic uses including insulin resistance and obesity. FDA found insufficient effectiveness and safety evidence.

What MOTS-c Is

MOTS-c is a 16-amino-acid mitochondrial-derived peptide discovered in 2015. It is proposed to act through AMPK-dependent mechanisms and is marketed — alone and in combination — as an injectable for metabolic and performance uses. For context on metabolic peptides and exercise mimetics, see our SLU-PP-332 overview.

Characterization and Immunogenicity Flag

FDA reported lyophilized MOTS-c (free base) as stable below −20°C when desiccated and protected from light. But the agency flagged that compounded MOTS-c may pose significant immunogenicity risk when injected, owing to potential aggregate formation and peptide-related impurities — and that the nominator did not provide the information needed to address it.

Historical Use: No Documented Human Compounding

Published literature revealed no studies in which compounded MOTS-c or MOTS-c acetate were used in humans, and outsourcing facilities did not report compounding it. Internet marketing presents MOTS-c mainly as an injectable, alone and combined with other substances, for numerous uses — but documented compounding history was not established.

Effectiveness: Rodent Mechanism, No Human Outcomes

FDA acknowledged nonclinical studies suggesting MOTS-c, acting via AMPK-dependent mechanisms, could improve glucose handling and other metabolic endpoints in rodent models. But it concluded there is a lack of evidence to evaluate effectiveness for the MOTS-c-related nominated uses in humans, and it noted FDA-approved therapies exist for some nominated indications.

Safety: No Human Data

FDA cited a lack of clinical and nonclinical safety information and was "particularly concerned" about the absence of human data by any route. As a 16-amino-acid peptide, MOTS-c lacks the information needed to assess its immunogenic risk, so potential human safety risks remain unknown.

What It Means for Physicians

MOTS-c was not FDA-approved and remains so. With no monograph and no approved-drug status, the 503A Bulks List was the pathway at issue — and FDA proposes to keep it closed. See the pillar overview and confirm access with your 503A compounding partner.

Key Takeaways

• FDA is proposing that MOTS-c (free base and acetate) not join the 503A Bulks List.
• Metabolic benefits are reported in rodents via AMPK mechanisms, but no human effectiveness data exist.
• No documented human compounding use was found.
• Immunogenicity from injection is a specific, unaddressed concern; FDA-approved metabolic therapies already exist.

Frequently Asked Questions

Is MOTS-c banned by the FDA?
No. FDA is proposing that MOTS-c not be added to the 503A Bulks List — an advisory-committee proposal, not a final determination. MOTS-c was never FDA-approved.

What is MOTS-c?
A 16-amino-acid mitochondrial-derived peptide discovered in 2015, proposed to act through AMPK-dependent pathways.

What was MOTS-c nominated to treat?
Metabolic uses including insulin resistance and obesity, by the injectable route.

Is there human evidence MOTS-c works?
No. FDA found the metabolic effects in rodent models but concluded there is a lack of evidence to evaluate effectiveness in humans.

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