Efficacy and Safety of Semaglutide in Obese Patients with Heart Failure with Preserved Ejection Fraction: A Systematic Review and Meta-Analysis

<p><strong>Abstract </strong></p> <p><strong>Background:</strong><br />Heart failure with preserved ejection fraction (HFpEF) affects nearly half of heart failure patients, with over 80% being either overweight or obese. Obesity is strongly associated with the pathogenesis of HFpEF, exacerbating diastolic dysfunction. Despite available therapies, effective treatments are limited, particularly in obese individuals. This systematic review and meta-analysis aimed to evaluate the safety and efficacy of semaglutide in obese patients with HFpEF.</p> <p><strong>Methods:</strong><br />A comprehensive literature search was conducted in PubMed, Google Scholar, and the Cochrane Library, adhering to PRISMA guidelines. Three studies (2 RCTs and 1 observational study) with 1,463 patients (677 in the semaglutide group, 786 in placebo) were included. Outcomes included percentage change in body weight, 6-minute walk distance, heart failure hospitalizations, cardiovascular mortality, and quality of life improvements. A random effects model was used, and heterogeneity was assessed using I² statistics.</p> <p><strong>Results:</strong><br />The meta-analysis demonstrated that semaglutide significantly reduced body weight (MD = -6.68; P = 0.0006) and improved 6-minute walk distance (MD = 16.37; P < 0.00001). Semaglutide also substantially reduced the risk of heart failure hospitalizations (RR = 0.28; P = 0.0005). However, no statistically significant reduction was observed in cardiovascular mortality (RR = 0.27; P = 0.16). Additionally, patients experienced significant improvements in quality of life, as measured by the Kansas City Cardiomyopathy Questionnaire clinical summary score (KCCQ-CSS) (RR = 0.30; P < 0.0001).</p> <p><strong>Conclusion:</strong><br />Semaglutide shows promising effects in improving clinical outcomes, particularly in reducing body weight, enhancing functional capacity, and lowering heart failure-related hospitalizations in obese HFpEF patients. However, its impact on cardiovascular mortality remains inconclusive, warranting further research.</p>