Cardiovascular Effects of Semaglutide in Patients with Heart Failure with Preserved Ejection Fraction: A Systematic Review and Meta-Analysis

Background: Semaglutide has emerged as an effective medication for treating type 2 diabetes mellitus (DM). However, the cardiovascular effects and safety of this agent in patients with heart failure with preserved ejection fraction (HFpEF) are unclear. Objective: This systematic review and meta-analysis aimed to assess the clinical and laboratory effects of semaglutide compared to placebo in patients with HFpEF. Methods: We systematically searched EMBASE, PubMed, and Cochrane databases for randomized controlled trials (RCTs) and non-randomized cohorts, from inception to July 2024, comparing semaglutide versus placebo in patients with HFpEF. Statistical analyses were performed using R Studio 4.3.2. Mean difference (MD) and odds ratio (OR) with 95% confidence intervals (CIs) were pooled across trials. Results: This meta-analysis included three studies, two RCTs and one non-randomized cohort, reporting data on 1463 patients. The follow-up time of the studies was 52 weeks. Compared to placebo, the use of semaglutide was associated with a significant increase in the 6-min walk distance (MD 16.20; 95% CI 10.19–22.21; p < 0.01; I2 = 0%). Additionally, reductions were observed in systolic blood pressure (MD −2.22; 95% CI −3.60 to −0.83; p < 0.01; I2 = 0%), C-reactive protein level (MD 0.59; 95% CI 0.49–0.70; p < 0.01; I2 = 51%), and N-terminal prohormone of brain natriuretic peptide (NT-proBNP) levels (MD 0.81; 95% CI 0.74–0.89; p < 0.01; I2 = 0%). Conclusion: These findings suggest that the use of semaglutide is associated with clinical and laboratory benefits in patients with HFpEF.