In nearly 5,500 obese patients with heart failure with preserved ejection fraction, GLP-1 receptor agonists were associated with fewer heart failure events, hospitalizations, and deaths compared to bariatric surgery, with similar weight loss.
29% lower all-cause deathGLP-1 receptor agonists were associated with 29% lower mortality (HR 0.71) compared to bariatric surgery in obese patients with heart failure, despite achieving similar weight loss — suggesting benefits beyond weight reduction alone.
What the researchers found
Among 2,747 propensity-matched patients per group (mean age 68), GLP-1 RA therapy showed significant advantages over bariatric surgery:
- Acute heart failure events: 38.9% vs 44.6% (HR 0.78, 95% CI 0.72-0.85) — 22% lower
- All-cause death: 11.1% vs 14.8% (HR 0.71, 95% CI 0.61-0.82) — 29% lower
- All-cause hospitalizations: 66.4% vs 77.3% (HR 0.62, 95% CI 0.58-0.66) — 38% lower
- Myocardial infarction: similar between groups (HR 0.99)
- Stroke: similar between groups (HR 0.87, not significant)
Weight loss was comparable: mean BMI at follow-up was 38.0 (GLP-1 RA) vs 37.7 (surgery), with no significant difference. However, blood sugar control was better after surgery (HbA1c 6.8 vs 7.4, P<0.001).
Why it matters
Heart failure with preserved ejection fraction (HFpEF) is the most common form of heart failure and is strongly linked to obesity. While bariatric surgery is effective for weight loss, it carries surgical risks and is not accessible to all patients. If GLP-1 medications can achieve equal or better cardiovascular outcomes through a non-surgical approach, it could transform how this increasingly common condition is managed — particularly for older or higher-risk patients who are poor surgical candidates.
How the study worked
Retrospective cohort study using the TriNetX multicenter research network. Adults aged 18+ with heart failure with preserved ejection fraction and obesity (BMI >30) from 2017-2022 were divided into two groups: those receiving GLP-1 RAs (semaglutide or tirzepatide) and those who underwent bariatric surgery. Propensity score matching (1:1) balanced baseline characteristics. Cox proportional hazard models estimated hazard ratios for cardiovascular outcomes.
What this study cannot tell us
This is a retrospective observational study, which cannot prove causation. Despite propensity matching, unmeasured confounders may exist — including selection bias (patients who received surgery vs. medication may differ in ways not captured). The TriNetX database has inherent coding limitations. Blood sugar control was better with surgery, suggesting the two groups may have differed metabolically. The study period (2017-2022) included early semaglutide and tirzepatide adoption, which may not reflect current prescribing practices.
How to read the evidence
This is a large retrospective cohort study with propensity-matched controls from a multicenter database. While it provides substantial real-world comparative evidence (5,494 matched patients), it is observational and subject to unmeasured confounding. It ranks below randomized controlled trials but provides strong hypothesis-generating data.
When this study was published
Published in 2025, this is a very recent study that directly addresses one of the most relevant clinical questions in cardiology today — how GLP-1 medications compare to established surgical interventions for obese heart failure patients.
The bigger picture
This study joins a growing body of evidence suggesting GLP-1 receptor agonists have cardiovascular benefits that go beyond weight loss alone — possibly through direct anti-inflammatory and cardiac protective effects. The finding that GLP-1 RAs outperformed bariatric surgery on hard outcomes like death and hospitalization, despite similar weight loss, strengthens the case for these medications as first-line therapy for obese patients with HFpEF. However, prospective randomized trials are needed to confirm these observational findings.
Questions still open
- Do GLP-1 receptor agonists provide direct cardiac protective effects beyond weight loss in heart failure patients?
- Would a prospective randomized trial comparing GLP-1 RAs to bariatric surgery in HFpEF patients confirm these observational findings?
- Should GLP-1 RA therapy be recommended as a first-line alternative to bariatric surgery for obese HFpEF patients who are poor surgical candidates?
Common questions
Are GLP-1 medications like semaglutide better than weight-loss surgery for heart failure?
If the weight loss was similar, why did GLP-1 medications have better heart outcomes?
Read the original research
Glucagon-Like Peptide-1 Receptor Agonists Versus Bariatric Surgery in Patients With Obesity and Heart Failure With Preserved Ejection Fraction.
Journal of the American Heart Association, 14(24), e044577
Citation
Ibrahim, Ramzi; Han, William; Wang, Winston; Kau, Ethan; Said, Nada; Forst, Beani; Pham, Hoang N; Abdelnabi, Mahmoud; Salih, Mohammed; Ali, Nima B; Farina, Juan; Lester, Steven J; Lee, Kwan; Ayoub, Chadi; Arsanjani, Reza. (2025). Glucagon-Like Peptide-1 Receptor Agonists Versus Bariatric Surgery in Patients With Obesity and Heart Failure With Preserved Ejection Fraction.. Journal of the American Heart Association, 14(24), e044577. https://doi.org/10.1161/JAHA.125.044577