Tirzepatide reduces the predicted risk of atherosclerotic cardiovascular disease and improves cardiometabolic risk factors in adults with obesity or overweight: SURMOUNT‐1 post hoc analysis

Abstract Aim To assess the effect of tirzepatide on long‐term risk of atherosclerotic cardiovascular disease (ASCVD) among people with obesity or overweight without diabetes from SURMOUNT‐1. Materials and Methods SURMOUNT‐1, a phase 3 trial, evaluated the efficacy and safety of tirzepatide in adults with body mass index ≥30 or ≥27 kg/m 2 and at least one weight‐related complication, excluding diabetes. Participants were randomly assigned to tirzepatide (5/10/15 mg) or placebo. Changes from baseline in cardiometabolic variables were assessed. The predicted 10‐year ASCVD risk scores were calculated (American College of Cardiology/American Heart Association risk engine) at baseline, week 24, and week 72 in SURMOUNT‐1 participants without a history of ASCVD. Percent change in risk scores from baseline to weeks 24 and 72 was compared between tirzepatide and placebo using mixed model for repeated measures analysis. Analyses were also conducted in participants with intermediate to high risk at baseline. Results Tirzepatide‐treated groups demonstrated reductions in cardiometabolic variables over 72 weeks. In participants without a history of ASCVD (N = 2461), the baseline median risk score was low and did not differ across groups (1.5%–1.6%). Relative change in risk from baseline to week 72 was greater for tirzepatide (−23.5% to −16.4%) than placebo (12.7%; P < 0.001). Relative change among participants with intermediate‐to‐high baseline risk was significantly greater for tirzepatide ( P < 0.05). Intermediate‐to‐high‐risk participants demonstrated similar relative change but greater absolute risk reduction compared to the overall population. Conclusion Tirzepatide treatment significantly reduced the 10‐year predicted risk of ASCVD versus placebo in patients with obesity or overweight without diabetes.