Triple agonist — Phase 2 trials showed 24% average weight loss at 48 weeks.
Retatrutide is Eli Lilly's next-generation weight loss peptide — a triple agonist of GLP-1, GIP, and glucagon receptors. Phase 2 trials published in the New England Journal of Medicine (2023) showed 24.2% average weight loss at 48 weeks, the highest ever recorded for a pharmacological obesity treatment. As of 2025, Phase 3 trials are ongoing.
Mechanism: Triple receptor agonism adds glucagon activity to the GLP-1/GIP dual mechanism. Glucagon receptor activation increases energy expenditure and fat oxidation (thermogenic effect), potentially explaining the superior weight loss vs dual agonists alone. This combination also shows significant effects on liver fat reduction.
| Week | Dose | Notes |
|---|---|---|
| 1–4 | 1 mg/week | Starting dose — always begin here |
| 5–8 | 2 mg/week | |
| 9–12 | 4 mg/week | |
| 13–16 | 6 mg/week | Mid-range |
| 17–20 | 8 mg/week | |
| 21+ | 12 mg/week | Maximum studied dose |
Retatrutide is not yet FDA-approved (Phase 3 trials as of 2025). Compounded versions are available but not validated against clinical trial formulations. Titrate slowly — the glucagon component adds thermogenic effects that can cause nausea and increased heart rate, especially early. The Phase 2 protocol used 4-week titration steps. This calculator uses compounded vial reconstitution.