Semaglutide in Patients with Obesity and Heart Failure Irrespective of Their Baseline Ejection Fraction: An Efficacy and Safety Meta-analysis of Randomized Controlled Trials

Obesity in heart failure (HF) patients often experience a significant burden of symptoms and physical limitations. Semaglutide, a glucagon-like peptide 1 receptor agonist, has a beneficial impact on cardiovascular outcomes in obese patients, but its role in patients with HF remains unclear. In our meta-analysis, we aimed to evaluate the safety and efficacy of semaglutide in obese HF patients. Five databases were searched from inception to August 2024 to identify randomized controlled trials (RCTs) that compared semaglutide to placebo in obese patients with HF regardless of the baseline ejection fraction (EF). Our primary outcome was the incidence of cardiovascular (CV) mortality. We performed a main subgroup analysis based on the ejection fraction [heart failure with preserved ejection fraction (HFpEF) and HF with reduced EF (HFrEF)]. Five RCTs with a total of 6898 patients were included in our meta-analysis. Semaglutide significantly reduced the overall incidence of CV mortality compared with placebo [risk ratio (RR), 0.74; 95% confidence interval (CI), 0.58-0.94; P = 0.02]. Similar rates were observed in HFrEF patients (RR, 0.66; 95% CI, 0.47-0.92; P = 0.01), without difference in HFpEF patients (RR, 0.84; 95% CI, 0.59-1.22; P = 0.37). Moreover, semaglutide demonstrated a positive impact on KCCQ-CSS [mean difference (MD), 7.72; 95% CI, 5.28-10.17; P < 0.001] and 6-minute walk test (MD, 14.83; 95% CI, 4.23-25.43; P = 0.006) compared with placebo. Semaglutide exhibited a significant reduction in CV mortality and improvement in the Kansas City Cardiomyopathy Questionnaire-Clinical Summary Score and 6-minute walk distance. Long-term RCTs are warranted to validate the current findings in obese HF patients.