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Mangiola F, Ianiro G, Franceschi F, Fagiuoli S, Gasbarrini G, Gasbarrini A

25 mg/day oral Tirzepatide 15 mg/week Retatrutide 12 mg/week Liraglutide 3.0 mg/day Factor Peak trial weight loss Semaglutide -14.9% at 68 wks (STEP 1) Tirzepatide -22.5% at 72 wks (SURMOUNT-1) Retatrutide -28.7% at 68 wks (TRIUMPH-4) Liraglutide -8% at 56 wks (SCALE) Factor FDA status (June 2026) Semaglutide Approved (T2D, obesity, CVD, MASH, CKD, oral) Tirzepatide Approved (T2D, obesity) Retatrutide Investigational - Phase 3 Liraglutide Approved (Saxenda obesity, Victoza T2D) Factor CV outcomes data Semaglutide Yes - SELECT (20% MACE drop) Tirzepatide SURPASS-CVOT ongoing Retatrutide TRIUMPH-3 ongoing Liraglutide Yes - LEADER (13% MACE drop) These compounds are not interchangeable

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