MOTS-c is an effective target for treating metabolic dysfunction: first-in-human clinical trial — VialBase Research

Summary

The first-in-human clinical trial of MOTS-c, conducted in obese, insulin-resistant postmenopausal women. This proof-of-concept study demonstrated that exogenous MOTS-c administration improves insulin sensitivity and is well-tolerated, providing the first human clinical validation of preclinical metabolic findings.

Key Findings

• MOTS-c significantly improved insulin sensitivity in obese postmenopausal women
• Enhanced skeletal muscle glucose uptake (measured by PET/CT)
• Improved beta-cell function and glucose disposal
• Well-tolerated with no serious adverse events reported
• Effects observed within a short treatment window (2 weeks)
• Validates the preclinical metabolic findings in humans for the first time

Methodology

First-in-human, open-label clinical trial in 10 obese, insulin-resistant postmenopausal women. MOTS-c administered daily (subcutaneous injection) for 14 days. Primary outcomes: insulin sensitivity (hyperinsulinemic-euglycemic clamp), skeletal muscle glucose uptake (18F-FDG PET/CT), oral glucose tolerance. Pre-post comparison design.

Limitations

• Very small sample size (n=10) — proof of concept only
• No placebo control (open-label, pre-post design)
• Single demographic group (obese postmenopausal women)
• Very short duration (14 days)
• No body composition or weight loss outcomes
• Longer-term safety data needed

Relevance to Content

Critically important — this elevates MOTS-c from “mouse data only” to “first human evidence.” The fact that it’s published in Cell Metabolism (top-tier journal) adds credibility. Content can now say “first-in-human data shows…” rather than relying solely on animal studies. This changes the evidence tier for MOTS-c content significantly.

See Also

• Parent compound: MOTS-c