MOTS-c and the 503A Bulks List: FDA's Review and the July 2026 PCAC Vote

Update (October 2026): At the July 23, 2026 meeting, the Pharmacy Compounding Advisory Committee voted 7–5 (2 abstentions) to recommend adding MOTS-c (free base and acetate) to the 503A Bulks List, going against the FDA staff proposal. The vote is advisory: MOTS-c is not on the 503A Bulks List until FDA completes notice-and-comment rulemaking, which is expected to run into 2027, and FDA can still decline to list it. For current status, see our FDA Peptide Status Tracker.

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 The nomination (later withdrawn, with FDA proceeding) sought MOTS-c by the injectable route for metabolic uses including insulin resistance and obesity.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.

Track Live FDA Peptide Status

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