MOTS-c to improve insulin sensitivity in adults with prediabetes and overweight or 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

This 12-week test will see if the investigational peptide MOTS-c can improve insulin sensitivity in adults with prediabetes who are overweight or have obesity.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 120 (estimated)
• Ages: 18 Years to 65 Years
• Sex: All
• Sponsor: Hudson Biotech (industry)
• Locations: 1 site (Shenzhen, Guangdong)
• Trial ID: NCT07505745 on ClinicalTrials.gov

What this trial studies

MOTS-c is a mitochondrial-derived peptide thought to regulate insulin sensitivity, with preclinical work suggesting effects on skeletal muscle and activation of AMPK. In this randomized, double-blind Phase 2a study, adults with prediabetes and BMI 27–40 kg/m2 are assigned 1:1 to subcutaneous MOTS-c or placebo and receive standardized lifestyle counseling. Efficacy is measured primarily by an OGTT-derived insulin sensitivity index and secondarily by HbA1c, fasting glucose, lipids, body weight, and waist circumference. Safety is monitored through adverse events, vital signs, ECG, labs, and a 4-week post-treatment follow-up.

Who should consider this trial

Good fit: Adults 18–65 years old with BMI 27.0–40.0 kg/m2 and laboratory-confirmed prediabetes who can maintain stable diet and activity and agree to study procedures are ideal candidates.

Not a fit: People with established diabetes, those taking glucose-lowering drugs, or individuals outside the specified age or BMI ranges are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, MOTS-c could improve insulin sensitivity and lower cardiometabolic risk in people with early metabolic dysfunction, potentially slowing progression to type 2 diabetes.

How similar studies have performed: Preclinical studies in cells and animal models have shown MOTS-c improves insulin sensitivity, but human data are limited and this Phase 2a trial represents early clinical testing.

Eligibility criteria

Inclusion Criteria:

* Age 18 to 65 years at the time of consent.
* Body mass index (BMI) 27.0 to 40.0 kg/m\^2.
* Prediabetes documented at screening by any of the following: (a) HbA1c 5.7% to 6.4%; (b) fasting plasma glucose 100 to 125 mg/dL; or (c) 2-hour plasma glucose 140 to 199 mg/dL during a 75 g OGTT.
* Stable body weight (less than 5% change) for at least 3 months prior to screening.
* Willingness to maintain stable diet and physical activity patterns during the 12-week treatment period.
* For participants of childbearing potential: agreement to use highly effective contraception for the study duration and for a protocol-specified period after last dose.
* Ability to understand and sign informed consent.

Exclusion Criteria:

* Diabetes mellitus (e.g., HbA1c 6.5% or higher, fasting plasma glucose 126 mg/dL or higher, or 2-hour glucose 200 mg/dL or higher at screening).
* Use of glucose-lowering medications (including metformin, GLP-1 receptor agonists, SGLT2 inhibitors) within 3 months prior to screening.
* History of bariatric surgery or planned weight-loss surgery during the study period.
* Clinically significant cardiovascular disease within 6 months (e.g., myocardial infarction, stroke, unstable angina) or uncontrolled hypertension.
* Estimated glomerular filtration rate (eGFR) \< 60 mL/min/1.73 m\^2, clinically significant hepatic disease, or ALT/AST \> 2.5x upper limit of normal at screening.
* Active malignancy requiring treatment (except adequately treated non-melanoma skin cancer).
* Pregnant, breastfeeding, or planning pregnancy during the study period.
* Known hypersensitivity to peptide therapeutics or any component of the investigational product formulation.
* Any condition that, in the investigator's judgment, would interfere with study participation or interpretation of results (e.g., inability to comply with study procedures).

Where this trial is running

Shenzhen, Guangdong

• Peking University Shenzhen Hospital — Shenzhen, Guangdong, China (RECRUITING)

Study contacts

• Study coordinator: Seni S Lu, Phd

Conditions: Prediabetes, Insulin Resistance, Overweight/Obesity, MOTS-c, mitochondrial-derived peptide, MDP, insulin sensitivity, AMPK