In a large real‑world study, people with obesity and a type of heart failure called HFpEF who took GLP‑1 drugs like semaglutide did better than those who had weight‑loss surgery. They had fewer heart‑failure flare‑ups, lived longer, and spent less time in the hospital, while losing about the same amount of weight. This suggests GLP‑1 drugs can be a powerful, non‑surgical option for managing weight and heart health in this high‑risk group.

To compare the effectiveness of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) versus bariatric surgery on cardiovascular outcomes in patients with heart failure (HF) with preserved ejection fraction and obesity. Using the TriNetX research network, we conducted a retrospective cohort study of adults (aged &#x2265;18&#x2009;years) with HF with preserved ejection fraction and obesity (body mass index &gt;30 kg/m²) from 2017 to 2022. Patients were categorized into 2 cohorts: those receiving GLP-1 RAs (semaglutide or tirzepatide) and those who underwent bariatric surgery. Propensity score matching (1:1) was used to balance baseline characteristics. Primary outcomes included acute HF events and all-cause hospitalizations. Secondary outcomes included all-cause death, myocardial infarction, stroke, and follow-up body mass index. Cox proportional hazard models were used to estimate hazard ratios (HRs). A total of 2747 patients were included per cohort (mean age, 68&#x2009;years). GLP-1 RA therapy was associated with lower incidence of acute HF events (38.9% versus 44.6%; HR, 0.78 [95% CI, 0.72-0.85]), all-cause death (11.1% versus 14.8%; HR, 0.71 [95% CI, 0.61-0.82]), and all-cause hospitalizations (66.4% versus 77.3%; HR, 0.62 [95% CI, 0.58-0.66]). Rates of myocardial infarction (13.8% versus 13.4%; HR 0.99 [0.86-1.14]) and stroke (9.7% versus 10.7%; HR, 0.87 [0.74-1.02]) were similar between groups. Mean body mass index at follow-up was 38.0 in the GLP-1 RA cohort versus 37.7 after bariatric surgery (<i>P</i>=0.34). Hemoglobin A_1c at follow-up was higher in the GLP-1 RA group (7.4 versus 6.8; <i>P</i>&lt;0.001). In patients with HF with preserved ejection fraction and obesity, GLP-1 RA therapy was associated with improved outcomes compared with bariatric surgery, supporting the need for prospective trials to evaluate GLP-1 RAs as a therapeutic alternative.