Semaglutide significantly reduces NT-proBNP, improves symptoms, and lowers hospitalizations in obesity-related HFpEF

Heart failure with preserved ejection fraction (HFpEF), particularly when driven by obesity, is a growing clinical challenge marked by exercise intolerance and systemic inflammation. Current therapeutic options for this specific phenotype are limited, leaving a significant unmet need for effective treatments. Glucagon-like peptide-1 receptor (GLP-1R) agonists like semaglutide, already approved for obesity management, have shown promise in improving cardiometabolic markers and symptoms, making them a compelling area of investigation for HFpEF.

Researchers conducted a systematic review and meta-analysis of six randomized controlled trials (n=4,216 participants) comparing semaglutide against placebo in adults with HFpEF and obesity. The study systematically searched MEDLINE, Embase, and CENTRAL databases through February 2025 to identify relevant trials. Primary outcomes assessed included changes in N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels, Kansas City Cardiomyopathy Questionnaire (KCCQ) scores, and the incidence of heart-failure hospitalization. Pooled analyses utilized random-effects models to synthesize the data.

Semaglutide therapy demonstrated significant improvements across key cardiovascular markers and clinical outcomes. NT-proBNP levels were significantly reduced by semaglutide, showing a mean difference of -119.7 pg/mL (95% CI -144.4 to -95.1; P < 0.001). Symptomatic improvement was also notable, with KCCQ scores increasing by a mean difference of +8.27 points (95% CI 6.04-10.50; P < 0.001) in trials focusing on HFpEF populations. The most impactful finding for patient prognosis was the reduced risk of hospitalization.

Semaglutide was associated with a lower risk of heart-failure hospitalization, reflected by an odds ratio of 0.81 (95% CI 0.75-0.88; P < 0.001).

Between-study heterogeneity for these primary outcomes was low, and sensitivity analyses confirmed the robustness of the pooled estimates. Meta-regression analyses did not identify significant modification of treatment effects by baseline C-reactive protein levels.