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In head-to-head and pivotal trial data, tirzepatide 15 mg weekly (Zepbound) produces the largest average total body weight loss, in the low-20s percent range

Side-by-side compound comparison Receptor targets Tirzepatide GLP-1 + GIP (dual) Semaglutide GLP-1 only Retatrutide GLP-1 + GIP + Glucagon (triple) Half-life Tirzepatide ~5 days Semaglutide ~7 days Retatrutide ~6 days Dosing frequency Tirzepatide Once weekly Semaglutide Once weekly Retatrutide Once weekly Max studied dose Tirzepatide 15 mg / week Semaglutide 2.4 mg / week (Wegovy) Retatrutide 12 mg / week Peak weight loss Tirzepatide 22.5% (SURMOUNT-1, 72 wk) Semaglutide 15.8% (STEP-1, 68 wk) Retatrutide 24.2% (Phase 2, 48 wk) FDA status (June 2026) Tirzepatide Approved (T2D, obesity, OSA) Semaglutide Approved (T2D, obesity, CV risk) Retatrutide Investigational Phase 3 Head-to-head Tirzepatide 20.2% vs semaglutide 13.7% (SURMOUNT-5) Semaglutide Retatrutide Not yet head-to-head vs tirzepatide HFpEF benefit Tirzepatide Yes (SUMMIT, HR 0.62) Semaglutide Yes (STEP-HFpEF) Retatrutide Not yet studied Unique advantage Tirzepatide Best-in-class FDA-approved efficacy