MOTS-c for Improving Insulin Sensitivity in Adults With Prediabetes and Overweight/Obesity

Mitochondrial-derived peptides (MDPs) are small peptides encoded by mitochondrial DNA that can act as signaling molecules. MOTS-c (mitochondrial open reading frame of the 12S rRNA type-c) has been reported to regulate insulin sensitivity and metabolic homeostasis in preclinical studies, with skeletal muscle identified as a key target tissue and AMPK activation proposed as a downstream mechanism. Based on these findings, this trial is designed to test the hypothesis that MOTS-c can improve insulin sensitivity and cardiometabolic risk markers in humans with early metabolic dysfunction. The study includes a screening period (up to 4 weeks), a 12-week double-blind treatment period, and a 4-week post-treatment safety follow-up. Efficacy is assessed using a 75 g oral glucose tolerance test (OGTT)-derived insulin sensitivity index and standard metabolic endpoints (HbA1c, fasting glucose, lipids, body weight, and waist circumference). Safety assessments include adverse events, vital signs, ECG, and laboratory testing.