Retatrutide
GLP-1/GIP/Glucagon triple agonist, LY3437943
Overview
Retatrutide is an investigational triple agonist targeting GLP-1, GIP, and glucagon receptors simultaneously. Early clinical trials have shown remarkable weight loss outcomes, potentially surpassing existing GLP-1 therapies.
Research Summary
Retatrutide (LY3437943) is a once-weekly subcutaneous peptide developed by Eli Lilly. In Phase 2 trials (NEJM, 2023), participants achieved up to 24.2% body weight reduction over 48 weeks — among the highest ever recorded for an anti-obesity medication. Its triple receptor mechanism amplifies metabolic effects: GLP-1 reduces appetite and slows gastric emptying, GIP enhances insulin secretion, and glucagon increases energy expenditure. Phase 3 trials (TRIUMPH program) are currently underway.
Mechanism of Action
Simultaneous agonism of GLP-1 (glucagon-like peptide-1), GIP (glucose-dependent insulinotropic polypeptide), and glucagon receptors. This triple action suppresses appetite, enhances insulin secretion, and boosts energy expenditure — a synergistic metabolic effect beyond dual agonists like tirzepatide.
Common Discussion Topics
Dosing Guide
Research-based reference only. Not medical advice. Consult a qualified professional.
GIP/GLP-1/Glucagon triple agonist. Phase 2 trial used a 2 mg starting dose for the 8 mg and 12 mg arms. GI side effects were partially mitigated by starting at 2 mg vs 4 mg.
Phase 2 trial: 4 mg arm (total) achieved −17.1% weight loss at 48 weeks.
Phase 2 trial: 8 mg arm achieved −22.8% weight loss at 48 weeks. 91% of participants lost ≥5%, 75% lost ≥10%, 60% lost ≥15%.
Maximum Phase 2 dose. 12 mg arm: −24.2% weight loss at 48 weeks — the highest reported for any injectable anti-obesity peptide in Phase 2 data. Investigational — not FDA approved.
| Phase | Dose | Frequency | Notes & Sources |
|---|---|---|---|
| Weeks 1–4 | 2 mg2,000 mcg | Once weekly | GIP/GLP-1/Glucagon triple agonist. Phase 2 trial used a 2 mg starting dose for the 8 mg and 12 mg arms. GI side effects were partially mitigated by starting at 2 mg vs 4 mg. |
| Weeks 5–8 | 4 mg4,000 mcg | Once weekly | Phase 2 trial: 4 mg arm (total) achieved −17.1% weight loss at 48 weeks. |
| Weeks 9–16 | 8 mg8,000 mcg | Once weekly | Phase 2 trial: 8 mg arm achieved −22.8% weight loss at 48 weeks. 91% of participants lost ≥5%, 75% lost ≥10%, 60% lost ≥15%. |
| Week 17+ (Maintenance) | 12 mg12,000 mcg | Once weekly | Maximum Phase 2 dose. 12 mg arm: −24.2% weight loss at 48 weeks — the highest reported for any injectable anti-obesity peptide in Phase 2 data. Investigational — not FDA approved. |
Retatrutide is an investigational compound not approved by the FDA. All information is for research and educational purposes only. Not medical advice.
Discussion
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