Semaglutide vs Metabolic and Bariatric Surgery and Cardiovascular Outcomes in Obesity.

OBJECTIVES: To compare cardiovascular outcomes associated with metabolic and bariatric surgery (MBS) versus semaglutide therapy among adults with obesity, stratified by type 2 diabetes mellitus (T2DM) status. METHODS: This retrospective cohort study used the US Collaborative Network within TriNetX. Adults with obesity who initiated semaglutide therapy or underwent sleeve gastrectomy or Roux-en-Y gastric bypass between January 2018 and January 2025 were propensity score matched separately according to T2DM history. The primary outcome was a composite of coronary events, cerebrovascular events, heart failure, and cardiac arrest during follow-up of up to 5 years. Sensitivity analyses varied the follow-up horizon, post-index encounter requirements, semaglutide refill requirements, and the start of follow-up. RESULTS: After matching, each treatment group included 11,466 patients without T2DM and 7,327 patients with T2DM. MBS was associated with a lower risk of the composite cardiovascular outcome than semaglutide therapy among patients without T2DM (4.4% vs 6.6%; hazard ratio [HR], 0.402; 95% CI, 0.356-0.454) and with T2DM (9.0% vs 14.6%; HR, 0.421; 95% CI, 0.381-0.465). MBS was also associated with lower risks of coronary events, cerebrovascular events, and heart failure in both strata. The relative differences were greatest for heart failure (HR, 0.293 without a history of T2DM; HR, 0.346 with a history of T2DM). Findings remained directionally consistent across subgroup and sensitivity analyses. CONCLUSIONS: Among adults with obesity, MBS was associated with lower cardiovascular risk than semaglutide therapy, regardless of T2DM history. These findings provide real-world comparative evidence to inform individualized discussions of surgical and pharmacologic obesity treatment options.