Both are Eli Lilly incretin agonists, but retatrutide adds a third receptor — glucagon — to tirzepatide’s GIP/GLP-1 dual mechanism. Tirzepatide is FDA-approved; retatrutide is investigational. This page covers what the added glucagon agonism does and what the trials show.
Research reference only. Not medical advice, prescribing guidance, or a product recommendation.
| Dimension | Retatrutide | Tirzepatide |
|---|---|---|
| Receptor targets | GIP-R + GLP-1R + glucagon-R | GIP-R + GLP-1R |
| Agonism class | Triple agonist | Dual agonist ("twincretin") |
| Developer | Eli Lilly (LY3437943) | Eli Lilly |
| Approval status | Investigational (Phase 3 — TRIUMPH program) | FDA approved (Mounjaro 2022 · Zepbound 2023) |
| Peak weight ↓ (trial) | ~24% (Phase 2, 48 wk, highest dose) | ~22.5% (SURMOUNT-1, 72 wk, 15 mg) |
| Glucagon arm | Adds energy expenditure + hepatic lipolysis | None |
| Maturity of evidence | Phase 2 complete; Phase 3 ongoing | Multiple completed Phase 3 trials |
~24% vs ~2% (placebo)
Mean body-weight change · n=338 · 48 wk — Jastreboff et al., NEJM 2023; highest-dose arm
−22.5% vs −2.4% (placebo)
Mean body-weight change · n=2539 · 72 wk — Pivotal obesity trial for Zepbound
In progress — not yet reported
Phase 3 efficacy/safety · Ongoing — Approval depends on these outcomes
Retatrutide’s triple mechanism produced the largest weight reduction reported among incretin agonists in Phase 2 (~24%), exceeding tirzepatide’s pivotal data — but the comparison is across different trials and stages, not a head-to-head, and retatrutide’s Phase 3 (TRIUMPH) results and full safety profile are still pending. Tirzepatide is the established, FDA-approved option with multiple completed Phase 3 trials. These are population means from trial data, not predictions for any individual.
Tirzepatide is a dual agonist of the GIP and GLP-1 receptors. Retatrutide is a triple agonist that adds glucagon-receptor agonism on top of GIP/GLP-1. The glucagon arm is associated with increased energy expenditure and hepatic lipolysis, and is the proposed basis for retatrutide’s larger weight-loss in Phase 2.
In Phase 2, retatrutide reported ~24% mean body-weight reduction at the highest dose, exceeding tirzepatide’s pivotal SURMOUNT-1 result (~22.5%). However, these are separate trials at different durations and stages — not a head-to-head comparison — and retatrutide’s Phase 3 results are not yet reported. Individual responses vary.
No. Retatrutide (LY3437943) is investigational and in Phase 3 trials (the TRIUMPH program). Tirzepatide is FDA-approved as Mounjaro (type 2 diabetes, 2022) and Zepbound (chronic weight management, 2023).
Beyond the appetite suppression and glycemic control of GLP-1/GIP, glucagon-receptor agonism is studied for increased energy expenditure and hepatic lipolysis (liver-fat reduction). The trade-off is that glucagon can raise glucose, so a triple agonist must balance it against the insulinotropic GLP-1/GIP signals.