Semaglutide vs Metabolic and Bariatric Surgery and Cardiovascular Outcomes in Obesity

In adults with obesity, metabolic and bariatric surgery was associated with a lower risk of major cardiovascular events than semaglutide therapy, both in people with and without type 2 diabetes. The finding came from a US retrospective cohort study with up to 5 years of follow-up.

Journal article — Retrospective cohort study. Population: Adults with obesity who initiated semaglutide therapy or underwent sleeve gastrectomy or Roux-en-Y gastric bypass between January 2018 and January 2025, identified in the US Collaborative Network within TriNetX. Sample size: Each treatment group included 11,466 patients without T2DM and 7,327 patients with T2DM after matching. Follow-up: Up to 5 years of follow-up. Interventions: Semaglutide therapy.

After propensity-score matching, each treatment group included 11,466 patients without T2DM and 7,327 patients with T2DM. Among patients without T2DM, the composite cardiovascular outcome occurred in 4.4% of the MBS group versus 6.6% of the semaglutide group (HR 0.402; 95% CI 0.356-0.454). Among patients with T2DM, the rates were 9.0% versus 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 difference was greatest for heart failure (HR 0.293 without T2DM; HR 0.346 with T2DM). Findings remained directionally consistent across subgroup and sensitivity analyses.

For researchers studying semaglutide, this paper provides real-world comparative evidence on cardiovascular outcomes against bariatric surgery in adults with obesity. It does not establish a causal treatment effect because it is observational, and it does not address semaglutide dose, adherence, or comparisons with other GLP-1 receptor agonists.

Key findings

• Among patients without T2DM, metabolic and bariatric surgery was associated with a lower risk of the composite cardiovascular outcome than semaglutide (4.4% vs 6.6%; HR 0.402; 95% CI 0.356-0.454).
• Among patients with T2DM, metabolic and bariatric surgery was associated with a lower risk of the composite cardiovascular outcome than semaglutide (9.0% vs 14.6%; HR 0.421; 95% CI 0.381-0.465).
• Metabolic and bariatric surgery was associated with lower risks of coronary events, cerebrovascular events, and heart failure in both T2DM strata.
• The relative difference was greatest for heart failure (HR 0.293 without T2DM; HR 0.346 with T2DM).
• Findings remained directionally consistent across subgroup and sensitivity analyses.

Limitations

• Retrospective cohort design means residual confounding is possible despite propensity-score matching.
• TriNetX electronic health record data may contain coding errors or incomplete outcome ascertainment.
• Semaglutide dose and long-term adherence are not reported; only sensitivity analyses around refill requirements are described.
• The study is limited to US adults within TriNetX, so generalizability to other settings is uncertain.

The record

• Journal: Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists: S1530-891X(26)01106-7
• Published: 2026-08-11
• PMID: 42580629 — DOI: 10.1016/j.eprac.2026.08.006
• Author countries: Taiwan

Peptide profiles: Semaglutide.

All indexed evidence: Semaglutide trials & papers.

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