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

What Was Tested

In this phase 2 trial, researchers set out to test MOTS-c for insulin resistance, prediabetes & type 2 diabetes.

Participants are randomized 1:1 to MOTS-c or placebo, receive standardized lifestyle counseling, and are followed for safety through Week 16.

It had two arms (groups): MOTS-c (experimental) and Placebo (placebo comparator).

Participants receive investigational MOTS-c plus standardized lifestyle counseling.

Participants receive matching placebo plus standardized lifestyle counseling.

The registry classes the interventions as drug and other.

More on the Plan

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.

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.

Safety assessments include adverse events, vital signs, ECG, and laboratory testing.

Who Took Part

Enrollment: 120 planned participants were the target.

It was open to people of any sex aged from 18 years up to 65 years.

Healthy volunteers were not accepted; participants needed the condition being studied.

Examples of who could join: Age 18 to 65 years at the time of consent. Body mass index (BMI) 27.0 to 40.0 kg/m\^2. Willingness to maintain stable diet and physical activity patterns during the 12-week treatment period. Ability to understand and sign informed consent.

The full record lists 7 inclusion and 9 exclusion criteria; among the exclusions: 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; active malignancy requiring treatment (except adequately treated non-melanoma skin cancer).

How the Study Was Run

The set-up was randomized, parallel-group and quadruple-blind.

The insulin resistance, prediabetes & type 2 diabetes participants were allocated by chance, so the MOTS-c group and the comparison group should start out alike.

Groups ran in parallel: each of the insulin resistance, prediabetes & type 2 diabetes participants stayed in one arm throughout.

Blinding on both sides kept the insulin resistance, prediabetes & type 2 diabetes participants and researchers unaware of who received MOTS-c.

Those kept unaware of assignments: participant, care provider, investigator and outcomes assessor.

It started in 2026-02-02 with completion listed for 2027-02-14.

It ran at 1 site in China.

Its stated primary purpose is treatment.

What Was Measured

The main thing measured (primary outcome): Change from baseline in OGTT-derived insulin sensitivity (Matsuda Index) (time frame: 12 Weeks). Incidence of treatment-emergent adverse events (TEAEs) (time frame: 16 weeks).

It also tracked 4 secondary outcomes, for example Change from baseline in HbA1c, Change from baseline in fasting glucose and Immunogenicity (anti-drug antibodies, if applicable).

What This Means in Plain Language

Put simply, this is a phase 2, randomized trial of MOTS-c in 120 people with insulin resistance, prediabetes & type 2 diabetes.

It is still recruiting; no results are posted to the registry yet, so nothing here describes outcomes.

More context: the MOTS-c compound page, Insulin resistance, prediabetes & type 2 diabetes research.