Effects of Semaglutide on Exercise Capacity and Health-Related Quality of Life In Obesity-Related Hfpef: A Systematic Review and Meta-Analysis

Obesity-related heart failure with preserved ejection fraction (HFpEF) is associated with reduced exercise capacity, impaired quality of life, and limited therapeutic options. Semaglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, has emerged as a potential treatment. To evaluate the effects of semaglutide on exercise capacity and health-related quality of life in patients with obesity-related HFpEF. This systematic review and meta-analysis followed the PRISMA 2020 guidelines and was registered in PROSPERO (CRD420261418825). Scopus, ScienceDirect, and Taylor & Francis were searched from database inception through June 30, 2026. Randomized controlled trials comparing semaglutide with placebo in patients with obesity-related HFpEF were included. Outcomes comprised the Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS), 6-minute walk distance (6MWD), and weight loss. Analyses were performed using Review Manager (RevMan) version 5.4. Two randomized controlled trials involving 1,145 participants were included. Compared with placebo, semaglutide significantly improved KCCQ-CSS (SMD = 0.32; 95% CI: 0.19–0.45; p < 0.00001; I² = 20%) and 6MWD (SMD = 0.18; 95% CI: 0.06–0.29; p = 0.003; I² = 0%). Semaglutide also significantly reduced body weight (SMD = −0.81; 95% CI: −1.24 to −0.38; p = 0.0002), although heterogeneity was high (I² = 92%). Semaglutide improved quality of life, exercise capacity, and weight loss in patients with obesity-related HFpEF. Further studies with larger samples and longer follow-up are needed to confirm its long-term benefits