Eli Lilly’s Mounjaro (tirzepatide) cleared an FDA approval aimed at reducing major cardiovascular events in adults with type 2 diabetes at high risk, building on cardiovascular outcomes data from the SURPASS-CVOT program. The decision extends tirzepatide’s role beyond glycemic control and weight outcomes, positioning it as a broad cardiometabolic option for an increasingly competitive GLP-1/GIP class. In SURPASS-CVOT, Mounjaro demonstrated non-inferiority to dulaglutide (Trulicity) on the time to first occurrence of a composite MACE endpoint. The primary comparison reported an 8% lower MACE-3 rate for tirzepatide versus Trulicity, with the hazard ratio for time to first MACE reported at 0.92 (95.3% CI: 0.83–1.01). Common adverse events remained largely consistent with the established gastrointestinal tolerability profile. The FDA’s approval matters for market access and sequencing as payers weigh cardiovascular benefit alongside weight and diabetes outcomes across incretin therapies.