NCT07505745

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

A Phase 2a, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy, Safety, and Pharmacodynamics of MOTS-c (a Mitochondrial-Derived Peptide) in Adults With Prediabetes and Overweight/Obesity

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 120 (estimated)
• Sponsor: Hudson Biotech · Industry
• Sex: All
• Age: 18 Years – 65 Years
• Healthy volunteers: Not accepted

Summary

This Phase 2a study evaluates whether 12 weeks of treatment with investigational MOTS-c improves insulin sensitivity compared with placebo in adults with prediabetes and overweight/obesity. Participants are randomized 1:1 to MOTS-c or placebo, receive standardized lifestyle counseling, and are followed for safety through Week 16.

Detailed description

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.

Conditions

• Prediabetes
• Insulin Resistance
• Overweight/Obesity

Interventions

Type	Name	Description
DRUG	MOTS-c (MDP)	Drug: MOTS-c (MDP)
DRUG	Placebo	Drug: Placebo
OTHER	Route Subcutaneous injection	injection
OTHER	Regimen	Fixed dose once daily for 12 weeks

Timeline

• Start date: 2026-02-02
• Primary completion: 2027-02-14
• Completion: 2028-05-17
• First posted: 2026-04-01
• Last updated: 2026-04-01

Locations

1 site across 1 country: China