Efficacy and safety of semaglutide in patients with heart failure: A meta-analysis

The pleiotropic effects of semaglutide make it a breakthrough therapy for managing diabetes and obesity, particularly in patients with comorbid cardiovascular diseases. However, its clinical application in heart failure (HF) remains under investigation. To systematically evaluate the efficacy and safety of subcutaneous semaglutide in the treatment of HF, irrespective of obesity status or the presence of type 2 diabetes mellitus (T2DM). A comprehensive search of the Cochrane Library, PubMed, Embase, China National Knowledge Infrastructure (CNKI), Wanfang, and VIP databases was conducted to identify randomized controlled trials (RCTs) of subcutaneous semaglutide in HF patients, from inception to November 2, 2024. RevMan 5.3 software was used for statistical analysis. A total of 4 RCTs involving 6109 patients were included. Four RCTs involving 6109 patients were included. Meta-analysis showed that, compared with placebo, subcutaneous semaglutide reduced the risks of cardiovascular death ( RR = 0.75, 95 % CI : 0.61–0.92, P = 0.005), all-cause mortality ( RR = 0.81, 95 % CI : 0.67–0.98, P = 0.03), and serious adverse events ( RR = 0.53, 95 % CI : 0.41–0.68, P < 0.00001). Subgroup analysis revealed that semaglutide improved Kansas City Cardiomyopathy Questionnaire clinical summary scores (KCCQ-CSS) ( MD = 7.58, 95 % CI : 4.40–10.77, P < 0.00001) and 6-minute walk test (6-MWT) distances ( MD = 16.91, 95 % CI : 8.98–24.83, P < 0.0001), and reduced the risk of HF rehospitalization ( RR = 0.41, 95 % CI : 0.26–0.65, P = 0.0001) in obese patients with HFpEF. Among patients without T2DM, semaglutide was superior to placebo in reducing HF rehospitalization ( RR = 0.16, 95 % CI : 0.04–0.68, P = 0.01) and cardiovascular mortality ( RR = 0.76, 95 % CI : 0.60–0.97, P = 0.03). Furthermore, at a dose of 2.4 mg weekly, semaglutide reduced HF rehospitalization ( RR = 0.29, 95 % CI : 0.14–0.58, P = 0.0005) and cardiovascular mortality ( RR = 0.75, 95 % CI : 0.59–0.95, P = 0.02) compared with placebo, whereas no significant benefit was observed at a dose of 1.0 mg weekly. Current evidence suggests that subcutaneous semaglutide safely and effectively reduces cardiovascular mortality, all-cause mortality, and serious adverse events in patients with HF, improves quality of life and exercise tolerance in obese HFpEF patients, and lowers the risk of HF rehospitalization. Nevertheless, given the limited number of included trials and patient populations, further high-quality studies are warranted to confirm these findings.