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Key Takeaways Tirzepatide vs semaglutide comes down to dual agonist vs single agonist: tirzepatide targets both GLP-1 and GIP receptors, while semaglutide targets GLP-1 alone The only head-to-head trial (SURPASS-2) found tirzepatide superior to semaglutide for both blood sugar control and weight loss In separate obesity trials, tirzepatide 15mg achieved 20.9% weight loss at 72 weeks vs semaglutide 2.4mg's 14.9% at 68 weeks Semaglutide has proven cardiovascular benefit (SELECT trial: 20% MACE reduction)