MOTS-c Peptide: Regulatory Status and Clinical Information
MOTS-c is not FDA-approved for any medical indication and remains an investigational compound with no established dosing or safety profile for clinical use. No guidelines from the American Diabetes Association, American Heart Association, or other major medical societies recommend MOTS-c for metabolic or age-related conditions 1.
Regulatory Status
- MOTS-c has no FDA approval for treatment of diabetes, obesity, cardiovascular disease, or any age-related condition 1.
- No established dosing regimens, formulations, or safety monitoring protocols exist for human therapeutic use 2, 3.
- MOTS-c is not mentioned in current diabetes treatment guidelines as a therapeutic option 1.
What MOTS-c Is
- MOTS-c is a 16-amino-acid mitochondrial-derived peptide encoded by the 12S rRNA region of mitochondrial DNA 2, 4.
- Under metabolic stress, MOTS-c translocates to the nucleus and regulates gene expression related to stress adaptation and antioxidant responses 5, 6.
- MOTS-c primarily acts through the Folate-AICAR-AMPK pathway to influence energy metabolism 5, 4.
- Plasma MOTS-c levels decline with age and are lower in metabolic conditions like obesity and diabetes 2, 3.
Research Findings (Not Clinical Recommendations)
- In rodent models, MOTS-c treatment prevented age-dependent and high-fat-diet-induced insulin resistance and reduced diet-induced obesity 4.
- Animal studies suggest MOTS-c may improve glucose metabolism in skeletal muscle and enhance insulin sensitivity 6, 4.
- Research indicates potential effects on cardiovascular disease, osteoporosis, and Alzheimer's disease in preclinical models, but no human clinical trials have established efficacy 2, 6.
Critical Clinical Context
- For metabolic conditions like type 2 diabetes, FDA-approved treatments include metformin, GLP-1 receptor agonists, SGLT2 inhibitors, DPP-4 inhibitors, and insulin—all with established safety profiles and dosing guidelines 1.
- For older adults with diabetes, treatment should prioritize agents with proven cardiovascular and renal benefits, such as GLP-1 receptor agonists and SGLT2 inhibitors 1.
- Glycemic targets for older adults should be individualized based on comorbidities, with A1C goals of 7.0-7.5% for healthy older adults and <8.0% for those with multiple chronic illnesses 1.
Why MOTS-c Cannot Be Recommended
- No human clinical trials have established safety, efficacy, or appropriate dosing for MOTS-c in any patient population 2, 3, 5.
- The peptide's pharmacokinetics, drug interactions, adverse effects, and long-term safety profile remain unknown 6.
- MOTS-c has not undergone the rigorous FDA approval process required for therapeutic agents 1.
What to Use Instead
- For insulin resistance and type 2 diabetes: Start with metformin (if eGFR ≥30 mL/min/1.73 m²), then add GLP-1 receptor agonists or SGLT2 inhibitors based on cardiovascular and renal comorbidities 1.
- For obesity management: FDA-approved GLP-1 receptor agonists (semaglutide, liraglutide) have demonstrated significant weight loss and cardiovascular benefits 1.
- For age-related metabolic decline: Focus on lifestyle interventions (physical activity, nutrition), continuous glucose monitoring when appropriate, and evidence-based pharmacotherapy 1.