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Achieving BMI <25 kg/m2 was associated with reduced predicted risk of atherosclerotic cardiovascular disease in people with obesity or overweight on tirzepatide or placebo: a post hoc analysis of SURMOUNT-1, -3, and -CN

Year: 2025

Type: article

Abstract: Background Effective weight reduction interventions may significantly reduce obesity-related atherosclerotic cardiovascular disease (ASCVD) risk. However, evidence on the association between optimal body mass index (BMI) target and long-term ASCVD risk was limited. Methods Pooled individual-level data from participants with obesity/overweight randomized to tirzepatide or placebo in SURMOUNT-1 (December 2019–April 2022; NCT04184622), -3 (March 2021–April 2023; NCT04657016), and -CN trials (September 2021–December 2022; NCT05024032) were analyzed. Ten-year ASCVD risk was calculated using the American College of Cardiology/American Heart Association Pooled Cohort Equations. A mixed model for repeated measures analysis was used to compare percent change in ASCVD risk from baseline by achieved BMI group (<25 kg/m 2 , ≥25 kg/m 2 ) at trial end, with terms including achieved BMI group, time point, achieved-BMI-group-by-time-point interaction, and baseline covariates. Findings Among 2691 participants included, 495 (18.4%) achieved BMI <25 kg/m 2 at trial end. In addition to a significantly higher proportion being treated with tirzepatide (98.2% vs 66.8%), the BMI <25 kg/m 2 group also had a higher proportion of females and lower mean BMI at baseline compared with the BMI ≥25 kg/m 2 group ( P < 0.001 for all). After adjusting for baseline covariates, relative to baseline, participants achieving BMI <25 kg/m 2 had a significantly greater percent reduction in predicted ASCVD risk (39.4% vs 10.6%, P < 0.001) compared to the BMI ≥25 kg/m 2 group. Among those with baseline intermediate-to-high ASCVD risk, reduction remained greater in the BMI <25 kg/m 2 group (25.6%) than the BMI ≥25 kg/m 2 group (9.0%; P < 0.001). Significantly greater improvements were also observed in blood pressure and lipids for the BMI <25 kg/m 2 group ( P < 0.001). Interpretation Achieving BMI <25 kg/m 2 , primarily with tirzepatide, was associated with a significantly greater 10-year ASCVD risk reduction compared with those whose BMI remained at 25 kg/m 2 or greater. These findings suggest potential cardiovascular benefits associated with targeting BMI <25 kg/m 2 in the long-term weight management. Funding This study was funded by Eli Lilly and Company.

Source: EClinicalMedicine

DOI: 10.1016/j.eclinm.2025.103722