Abstract
Disclosure: E. Palaparthi: None. R. Zeb: None. A. Morris: None. W. Banderas Echeverry: None. M. Tatineni: None. T. ,: None. S. Rajesh: None. A. Palacios: None. A. Malik: None. N. Ghanie: None. S. Naidoo: None. Background: Heart failure with preserved ejection fraction (HFpEF), often associated with obesity,poses a significant challenge in cardiovascular care. Semaglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, has demonstrated notable benefits in weight reduction and cardiometabolichealth. However, its impact on heart failure outcomes in obese HFpEF patients remains uncertain. Methods: This systematic review and meta-analysis followed PRISMA guidelines and includedpatients who received once-weekly semaglutide. Primary outcomes assessed were cardiovascularand all-cause mortality, heart failure hospitalizations, and weight loss. Data were analyzed usingrandom-effects models, with study quality evaluated through ROB 2.0 and Newcastle-OttawaScale tools. Results: Overall, four studies including a total of 1,999 HFpEF patients were included. Semaglutidewas associated with a reduction in cardiovascular mortality (OR 0.68, 95% CI [0..22–2.12], P=0.51)and all-cause mortality (OR 0.75, 95% CI, [0.36, 1.56], P = 0.45), though this was not statisticallysignificant. Significant improvements were observed for heart failure hospitalizations (OR 0.44,95% CI [0.28–0.67], P=0.0002), and congestive heart failure events (OR 0.13, 95% CI [0.05–0.33],P<0.0001). Semaglutide also led to substantial weight loss (MD -6.66%, 95% CI [-11.04, -2.29],P<0.00001) and waist circumference reduction at 52 weeks (MD -7.43 cm, 95% CI [-9.24, -5.61],P<0.00001). Secondary outcomes, including improvements in KCCQ score, 6-minute walkdistance, systolic BP, CRP, and BNP levels, were also statistically significant. Conclusion: Semaglutide significantly improves heart failure outcomes, all-cause mortality, andweight management in obese HFpEF patients. Its role in reducing cardiovascular mortalitywarrants further investigation.Keywords: Heart failure; preserved ejection fraction; semaglutide; glucagon-like peptide-1 (GLP-1)receptor agonist; obesity Presentation: Sunday, July 13, 2025