Semaglutide in Patients with Heart Failure with Preserved Ejection Fraction and Obesity

The STEP-HFpEF trial was a randomized, double-blind, placebo-controlled study evaluating the efficacy of once-weekly semaglutide 2.4 mg over 52 weeks in 529 patients with heart failure with preserved ejection fraction (HFpEF) and obesity (BMI ≥30). Dual primary endpoints were improvements in the Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS) and percentage change in body weight. Semaglutide yielded a mean KCCQ-CSS improvement of +16.6 points versus +8.7 with placebo (between-group difference: +7.8 points; P < 0.001), and weight loss of –13.3% vs –2.6% (difference: –10.7%; P < 0.001). Secondary endpoints favored semaglutide: 6-minute walk distance improved (+21.5 m vs +1.2 m), C-reactive protein (CRP) decreased (–43.5% vs –7.3%), and NT-proBNP levels fell (–20.9% vs –5.3%). Serious adverse events were lower in the semaglutide group (13.3% vs 26.7%). The trial established that semaglutide improves symptoms, physical function, inflammation, and cardiovascular markers in HFpEF patients with obesity, independent of diabetes status.

The STEP-HFpEF trial was a randomized, double-blind, placebo-controlled study evaluating the efficacy of once-weekly semaglutide 2.4 mg over 52 weeks in 529 patients with heart failure with preserved ejection fraction (HFpEF) and obesity (BMI ≥30). Dual primary endpoints were improvements in the Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS) and percentage change in body weight. Semaglutide yielded a mean KCCQ-CSS improvement of +16.6 points versus +8.7 with placebo (between-group difference: +7.8 points; P < 0.001), and weight loss of –13.3% vs –2.6% (difference: –10.7%; P < 0.001). Secondary endpoints favored semaglutide: 6-minute walk distance improved (+21.5 m vs +1.2 m), C-reactive protein (CRP) decreased (–43.5% vs –7.3%), and NT-proBNP levels fell (–20.9% vs –5.3%). Serious adverse events were lower in the semaglutide group (13.3% vs 26.7%). The trial established that semaglutide improves symptoms, physical function, inflammation, and cardiovascular markers in HFpEF patients with obesity, independent of diabetes status.