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

March 26, 2026 updated by: Hudson Biotech

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 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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Estimated)

120

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • China
    • Guangdong
      • Shenzhen, Guangdong, China, 518036

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: MOTS-c
Participants receive investigational MOTS-c plus standardized lifestyle counseling.
Drug: MOTS-c (MDP)
Drug: MOTS-c (MDP)
Other: Route Subcutaneous injection
injection
Other: Regimen
Fixed dose once daily for 12 weeks
Placebo Comparator: Placebo
Participants receive matching placebo plus standardized lifestyle counseling.
Drug: Placebo
Drug: Placebo
Other: Route Subcutaneous injection
injection
Other: Regimen
Fixed dose once daily for 12 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Incidence of treatment-emergent adverse events (TEAEs)
Time Frame: 16 weeks
16 weeks
Change from baseline in OGTT-derived insulin sensitivity (Matsuda Index)
Time Frame: 12 Weeks
12 Weeks

Secondary Outcome Measures

Outcome Measure
Time Frame
Change from baseline in HbA1c.
Time Frame: 12 Weeks
12 Weeks
Change from baseline in fasting glucose
Time Frame: 12 weeks
12 weeks
Change from baseline in 2-hour plasma glucose during 75 g OGTT.
Time Frame: 12 weeks
12 weeks
Immunogenicity (anti-drug antibodies, if applicable).
Time Frame: 16 weeks
16 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Hudson Biotech

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 2, 2026

Primary Completion (Estimated)

February 14, 2027

Study Completion (Estimated)

May 17, 2028

Study Registration Dates

First Submitted

March 14, 2026

First Submitted That Met QC Criteria

March 26, 2026

First Posted (Actual)

April 1, 2026

Study Record Updates

Last Update Posted (Actual)

April 1, 2026

Last Update Submitted That Met QC Criteria

March 26, 2026

Last Verified

March 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • EX-MOTS-2A-001

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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