MOTS-c: the first Phase 2a insulin-sensitivity trial is recruiting
A mitochondrial-encoded peptide with a large rodent literature now has a registered human trial. Results are not in yet.
MOTS-c is a 16-residue peptide encoded by mitochondrial 12S rRNA. Preclinical papers describe AMPK-related metabolic effects and “exercise-mimetic” language in mice. Until recently, that literature had no serious human efficacy trial.
The MOTS-MET study
ClinicalTrials.gov lists NCT07505745, a Phase 2a randomized, double-blind, placebo-controlled study in about 120 adults with prediabetes and overweight or obesity. Planned start: February 2026. Participants receive daily subcutaneous MOTS-c or placebo for 12 weeks. The primary endpoint is change in an OGTT-derived insulin-sensitivity index (Matsuda). Secondary measures include HbA1c, lipids, weight and waist circumference.
What a registry entry is not
A recruiting trial is a hypothesis test, not a result. It does not show that MOTS-c improves insulin sensitivity in people, and it does not make research-chemical MOTS-c a medicine.
Bottom line
Evidence ladder: Human pilot (trial underway). The interesting fact in 2026 is that someone is finally asking the clinical question under controlled conditions.
Sources
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