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

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.

Eligibility

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).

Conditions4

Interventions1

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