Efficacy of Semaglutide and Other GLP-1 Agonists in Patients with Heart Failure With Preserved Ejection Fraction and Obesity: A Systemic Review and Meta-Analysis

Semaglutide, a novel drug, has shown potential benefits for heart failure with preserved ejection fraction (HFpEF) and obesity in early trials. This study aims to evaluate the efficacy and safety of semaglutide and other glucagon-like peptide-1 (GLP-1) agonists in HFpEF patients with obesity. A comprehensive electronic search was conducted on October 18, 2024, using PubMed, Scopus, Web of Science, Embase, and Cochrane. Eligible studies included those comparing semaglutide or other GLP-1 agonists to placebo in this patient population. Primary outcomes included changes in 6-minute walking distance, Kansas City Cardiomyopathy Questionnaire clinical summary score (KCCQ-CSS), body weight, and secondary endpoints. Of 1116 studies, 4 met the inclusion criteria, comprising 2194 patients. GLP-1 agonists demonstrated a mean difference (MD) in 6-minute walking distance of 17.14 m [95% confidence interval (CI): 11.92-22.35, P < 0.001] and an MD in KCCQ-CSS of 7.3 (95% CI: 5.09-9.51, P < 0.001), indicating significant improvements in physical function and quality of life. Weight loss was substantial, with an MD of −7.19 kg (95% CI: −11.28 to −3.09, P = 0.001), alongside reduced inflammatory markers (C-reactive protein MD: −30.18, 95% CI: −38.16 to −22.2, P < 0.001). Hospitalizations or urgent care visits for heart failure were reduced (OR: 0.32, 95% CI: 0.15-0.66, P < 0.001). However, gastrointestinal adverse events leading to discontinuation were higher in the other GLP-1 agonists group (OR: 2.996, 95% CI: 1.683-5.331, P < 0.001). In HFpEF patients with obesity, GLP-1 agonists significantly improved symptoms, quality of life, physical function, and weight loss while reducing heart failure-related hospitalizations, though with increased gastrointestinal side effects.