NCT07505745 Phase 2a Trial: MOTS-c Insulin Sensitivity Research Data

NCT07505745 is a newly registered Phase 2a clinical trial testing whether investigational MOTS-c can improve insulin sensitivity in adults with prediabetes and overweight or obesity — the first human interventional study of this mitochondria-derived peptide outside a mitochondrial-disease indication. Registered under protocol EX-MOTS-2A-001 and sponsored by Hudson Biotech, the trial moves MOTS-c from a rodent-model literature base into a controlled human efficacy setting for the first time.

Research reference only. All information on this page is a summary of peer-reviewed scientific literature and a publicly registered clinical trial record, and does not constitute medical advice. See individual library profiles for full compound data.

Quick Answer: NCT07505745 is a randomized, double-blind, placebo-controlled Phase 2a trial (Hudson Biotech, 120 participants) testing whether 12 weeks of subcutaneous MOTS-c improves OGTT-derived insulin sensitivity (Matsuda Index) in adults with prediabetes and overweight/obesity; the study is currently enrolling with no results posted yet.

TL;DR:

First registered human interventional trial of MOTS-c for a metabolic (non-mitochondrial-disease) indication.
Phase 2a, randomized, quadruple-blind, placebo-controlled, 120 participants, 1:1 allocation, ages 18–65.
Primary endpoint: change in OGTT-derived insulin sensitivity (Matsuda Index) at 12 weeks; safety followed through week 16.
Sponsor is Hudson Biotech; status is currently enrolling, with no posted results as of this writing.
Mechanistic rationale draws on preclinical AMPK-activation and skeletal-muscle insulin-signaling data, not prior human efficacy trials.

What Was Announced

NCT07505745, titled "MOTS-c for Improving Insulin Sensitivity in Adults With Prediabetes and Overweight/Obesity" (internally designated MOTS-MET, protocol EX-MOTS-2A-001), has appeared in the ClinicalTrials.gov registry as a Phase 2a interventional study. The trial is sponsored by Hudson Biotech and is designed as a randomized, quadruple-blind, placebo-controlled, parallel-assignment study enrolling 120 participants.

Eligible participants are adults aged 18 to 65 with a BMI between 27.0 and 40.0 kg/m² and documented prediabetes — defined by HbA1c 5.7%–6.4%, fasting plasma glucose 100–125 mg/dL, or 2-hour plasma glucose 140–199 mg/dL on a 75 g oral glucose tolerance test (OGTT). Participants are randomized 1:1 to receive either subcutaneous investigational MOTS-c or matching placebo, both arms paired with standardized lifestyle counseling. The design includes a screening period of up to 4 weeks, a 12-week double-blind treatment period, and a 4-week post-treatment safety follow-up, for a total observation window of roughly 16 weeks.

This is a meaningful step for MOTS-c specifically because the compound's evidence base to date has been almost entirely preclinical. The peptide is encoded within the mitochondrial 12S rRNA gene region and has been studied in aged rodent models for its proposed role in AMPK activation and skeletal-muscle glucose handling. A 2026 study indexed under PMID 41945630 examined serum MOTS-c levels and the m.1382A>C polymorphism in adolescents with polycystic ovary syndrome, finding no statistically significant association between MOTS-c concentration and metabolic parameters in that specific cohort — a reminder that human data on MOTS-c and insulin-related endpoints has so far been limited and mixed, which is precisely the gap NCT07505745 is designed to address directly.

Affected Compounds

MOTS-c is the only compound under direct investigation in this trial, but it sits within a broader research cluster of mitochondria-derived and mitochondrial-support peptides that researchers frequently study together. The NAD+ library profile covers a parallel mitochondrial-adaptation pathway — NAD+/SIRT1 signaling — that converges with MOTS-c on AMPK activation, as detailed in the site's NAD+ and MOTS-C mitochondrial peptide research piece. The humanin library profile covers a third mitochondrially-encoded peptide studied for cytoprotective signaling, and is often discussed alongside MOTS-c in reviews of small mitochondrial-derived peptides (MDPs) as a signaling class.

None of these related compounds are named in the NCT07505745 protocol. They are relevant only as research context: MOTS-c's proposed mechanism (AMPK activation via skeletal-muscle signaling) is part of a wider mitochondrial-peptide literature that this trial's outcome will help clarify or complicate.

What This Changes for Research Access

NCT07505745 does not itself change MOTS-c's regulatory status. MOTS-c does not currently hold FDA approval for any indication, and its 503A compounding classification remains under review independent of this trial. What the trial does change is the evidence tier available to researchers: prior to this registration, essentially all human-relevant MOTS-c data came from observational studies like the PCOS cohort above, rather than from a controlled interventional design with a prespecified insulin-sensitivity endpoint.

Researchers tracking the trial's registry status, enrollment progress, or eventual results posting can use the clinical trial tracker tool on this site, which aggregates registry metadata for peptide compounds under active human investigation. Because the study is a Phase 2a signal-detection design rather than a pivotal Phase 3 program, a positive result would support further investigation rather than immediately establish clinical efficacy — the same interpretive caveat that applies to any early-phase trial.

Timeline and What's Next

As of this writing, NCT07505745 is listed as enrolling and has not posted results. The study's structure — a 4-week screening window, 12-week double-blind treatment period, and 4-week safety follow-up — means the earliest a completed dataset could plausibly exist is several months after the last participant is randomized, and posted results on the public registry would follow the standard reporting timeline required under federal clinical trial disclosure rules.

Researchers should watch for three registry milestones: a status change from "enrolling" to "active, not recruiting" once enrollment closes; the appearance of an estimated primary completion date once the enrollment target is met; and the eventual results posting under the trial's "Results" tab. Secondary endpoints — HbA1c, fasting glucose, 2-hour OGTT glucose, lipids, body weight, and waist circumference — will likely be reported alongside the primary Matsuda Index outcome, giving a fuller metabolic picture than the primary endpoint alone.

External Sources

Frequently asked questions

Q: What is NCT07505745 studying?

A: NCT07505745 is a Phase 2a randomized, placebo-controlled trial evaluating whether 12 weeks of investigational MOTS-c improves insulin sensitivity, measured by the OGTT-derived Matsuda Index, in adults with prediabetes and overweight or obesity. It is sponsored by Hudson Biotech and enrolls 120 participants.

Q: Is the MOTS-c NCT07505745 trial still recruiting?

A: As of this writing, the trial's registry status is listed as enrolling. Researchers can monitor status changes directly on the ClinicalTrials.gov record or via the site's clinical trial tracker tool, which flags registry updates as they occur.

Q: Has MOTS-c been tested in humans before this trial?

A: Human data on MOTS-c prior to NCT07505745 has come primarily from observational studies rather than controlled interventional trials. One indexed 2026 study (PMID 41945630) examined serum MOTS-c levels in adolescents with polycystic ovary syndrome and found no significant association with metabolic parameters in that cohort, underscoring how limited controlled human evidence has been until now.

Q: What is the Matsuda Index and why does this trial use it?

A: The Matsuda Index is a composite insulin-sensitivity measure derived from glucose and insulin values collected during a 75 g oral glucose tolerance test. It is a standard research endpoint for early-phase metabolic trials because it captures both hepatic and peripheral insulin sensitivity from a single test, rather than relying on fasting glucose alone.

Q: Does this trial affect MOTS-c's FDA or 503A compounding status?

A: No. NCT07505745 is a research trial and does not itself alter MOTS-c's regulatory classification. MOTS-c remains without FDA approval for any indication, and any changes to its 503A compounding status would come through separate FDA Pharmacy Compounding Advisory Committee review processes, not through this trial's registration or results.

See also:

MOTS-c: Mitochondria-Derived Peptide and Metabolic Regulator — the standalone MOTS-c research profile this trial summary builds on.
NAD+ and MOTS-C: Mitochondrial Peptide Research, AMPK Signaling & Metabolic Data — covers the shared AMPK/NAD+ signaling context referenced above.
MOTS-C, DSIP, Epitalon & Semax: PCAC Docket Research Summary — MOTS-c's separate 503A regulatory review track.

For laboratory research purposes only. Not for human or animal consumption. Compounds described are not approved by the FDA for human or veterinary use unless explicitly stated.