MOTS-c vs Orforglipron
Side-by-side comparison of key properties, dosing, and research.
Anti-Aging & Longevity
MOTS-cGLP-1 / Weight Loss Agonists
Orforglipron- Summary
- MOTS-c is a mitochondria-derived peptide (MDP) encoded within the mitochondrial genome. It acts as a metabolic regulator, improving insulin sensitivity, enhancing exercise capacity, and counteracting age-related metabolic decline. It is often called a 'mitochondrial hormone.'
- Orforglipron is an oral, once-daily small-molecule GLP-1 receptor agonist developed by Eli Lilly. Unlike injectable GLP-1 peptides, it is a non-peptide compound absorbed orally without food restrictions, representing a major convenience advancement. Phase 2 trials showed up to 9.4% weight loss at 36 weeks, and Phase 3 trials (ATTAIN program) are ongoing for obesity and type 2 diabetes.
- Half-Life
- Estimated 1–2 hours
- ~12 hours (once-daily oral dosing)
- Admin Route
- SubQ
- Oral
- Research
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- Typical Dose
- 5–15 mg
- 12 mg → 24 mg → 36 mg → 45 mg
- Frequency
- 3–5 times per week
- Once daily
- Key Benefits
- Improves insulin sensitivity and glucose metabolism
- Enhances exercise capacity and endurance
- Reduces age-related metabolic decline
- Activates AMPK — the master metabolic regulator
- Promotes fat oxidation
- Anti-inflammatory effects
- May extend healthspan via mitochondrial optimization
- Increases energy and reduces fatigue
- Oral pill — no injections required
- Once-daily dosing without food restrictions (unlike oral semaglutide)
- Up to 9.4% body weight reduction in Phase 2 at 36 weeks
- Significant HbA1c reduction in type 2 diabetes trials
- Small-molecule stability — no cold chain requirements
- Broadens access for injection-averse patients
- Potential class-defining convenience advantage over injectable GLP-1s
- Side Effects
- Injection site irritation
- Fatigue during initial adaptation
- Unknown long-term profile (limited human data)
- Nausea (most common, dose-dependent)
- Vomiting
- Diarrhea
- Decreased appetite
- +2 more
- Stacks With
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