The comparative effectiveness of bariatric operations versus GLP-1 RAs: a systematic review and meta-analysis.

BACKGROUND: Obesity is a global health crisis associated with increased morbidity and mortality, primarily due to cardiometabolic complications such as type 2 diabetes mellitus and cardiovascular disease. While glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have gained traction as pharmacologic interventions for weight loss and glycemic control, metabolic and bariatric surgery (MBS) remains a more established modality with durable long-term outcomes. Direct comparative effectiveness data evaluating their relative associations with mortality, cardiovascular outcomes, and glycemic control remain limited. OBJECTIVES: To systematically review and quantitatively synthesize observational comparative effectiveness evidence evaluating mortality, major adverse cardiovascular events, and glycemic outcomes among patients with obesity treated with MBS versus GLP-1 RA therapy. SETTING: Systematic review and meta-analysis of observational comparative effectiveness studies. METHODS: A systematic review and meta-analysis were performed on observational comparative effectiveness cohort studies evaluating outcomes among patients with obesity treated with either MBS or GLP-1 RAs. Two reviewers independently screened studies, extracted data, and assessed methodological quality using the Joanna Briggs Institute critical appraisal checklist. A systematic search of Medline (via PubMed), Embase, Web of Science, and the Cochrane Central Register of Controlled Trials was conducted in February 2025 to identify studies reporting all-cause mortality, major adverse cardiovascular events, or hemoglobin A1C outcomes. Pooled relative risks (RRs) for dichotomous outcomes and weighted mean differences (WMDs) for continuous outcomes were calculated using random-effects models. RESULTS: Six retrospective cohort studies involving 208,751 patients were included. In pooled analysis, MBS was associated with a significant reduction in major adverse cardiovascular events compared with GLP-1 RA therapy (RR = .59; 95% confidence interval [CI]: .46-.77). For all-cause mortality, MBS was associated with a nonsignificant trend toward lower risk compared with GLP-1 RA therapy (RR = .66; 95% CI: .41-1.07). The pooled WMD in final A1C favored MBS over GLP-1 RA therapy (WMD = -1.31%; 95% CI: -1.66 to .96). CONCLUSIONS: Both MBS and GLP-1 RA therapies provide important cardiometabolic benefits for individuals with obesity. MBS was associated with more favorable cardiovascular and glycemic outcomes, with a nonsignificant trend toward reduced all-cause mortality. Both treatment strategies remain important components of contemporary obesity management.