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Tirzepatide vs Retatrutide
Dual GLP-1/GIP agonist vs triple GLP-1/GIP/Glucagon agonist — what the Phase 2 data shows
Tirzepatide
Mounjaro / Zepbound
VS
Retatrutide
LY3437943 (Phase 3)
| Factor | Tirzepatide | Retatrutide |
|---|
| Mechanism |
Dual GLP-1 + GIP agonist |
Triple GLP-1 + GIP + Glucagon agonist |
| Avg Weight Loss |
20.9% (SURMOUNT Phase 3) |
24.2% (Phase 2, NEJM 2023) |
| Max Studied Dose |
15 mg/week |
12 mg/week |
| Starting Dose |
2.5 mg/week |
1 mg/week (cautious titration) |
| FDA Approval |
✅ Approved (Mounjaro/Zepbound) |
❌ Phase 3 trials ongoing (2025) |
| Liver Fat Reduction |
Strong |
Strongest studied (NASH potential) |
| Heart Rate Effect |
Mild increase |
More pronounced increase (glucagon) |
| GI Tolerance |
Good at standard titration |
Similar, titrate slowly for glucagon effects |
| Compounded Available |
Yes — widely available |
Yes — but less validated than Phase 3 data |
| Long-term Data |
Phase 3 complete, 2+ years data |
Phase 2 only — Phase 3 ongoing |
| Winner |
Proven, approved, widely available |
Greater weight loss potential when approved |
⚖️ The Verdict
Retatrutide's Phase 2 data is extraordinary — 24.2% average weight loss approaches bariatric surgery outcomes. The addition of glucagon receptor agonism adds meaningful thermogenic (calorie-burning) effects that tirzepatide lacks. However, Phase 2 data is not Phase 3 data. Tirzepatide has completed Phase 3 trials, is FDA-approved, and has robust real-world evidence. For most people in 2025-2026, tirzepatide remains the gold-standard approved option. Retatrutide is the most promising pipeline compound.
⚠️ Research purposes only. Not medical advice. Consult a licensed healthcare provider.