May 17, 2026Open Access
Semaglutide in Patients With Obesity and Heart Failure Across Mildly Reduced or Preserved Ejection Fraction
Key Result
Semaglutide 2.4 mg improved KCCQ Clinical Summary Score and reduced body weight to a similar extent across LVEF categories (45-49%, 50-59%, ≥60%) in patients with HFpEF and obesity.
Key Points
- This analysis aims to evaluate the effects of semaglutide in patients with obesity and heart failure across different levels of left ventricular ejection fraction (LVEF).
- 529 patients were randomized to semaglutide (263) or placebo (266) in the STEP-HFpEF trial.
- Patients categorized into groups based on LVEF: 45%-49%, 50%-59%, and ≥60%.
- Evaluation of primary and secondary endpoints after 52 weeks.
- Semaglutide improved Kansas City Cardiomyopathy Questionnaire scores significantly across all LVEF groups (EF 45%-49%: 5.0 points change, P interaction = 0.56).
- Body weight reduction was consistent across LVEF categories, with reductions of -7.6, -10.6, and -11.9 for respective groups (P interaction = 0.08).
- No significant influence of LVEF on other secondary endpoints like 6-minute walk distance and high-sensitivity C-reactive protein.
Study Design
Type
RCT (n=529)
Structured PICO
Does semaglutide improve symptoms and body weight in patients with the obesity phenotype of HFpEF across different LVEF strata?
P
Population
529 patients with the obesity phenotype of heart failure with preserved ejection fraction (HFpEF), categorized by baseline LVEF: 45% to 49% (n = 85), 50% to 59% (n = 215), and ≥60% (n = 229)
I
Intervention
Semaglutide 2.4 mg
C
Comparator
Placebo
O
Outcome
Dual primary endpoints of Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS) and body weight at 52 weekscomposite
Semaglutide 2.4 mg improves symptoms, physical limitations, and body weight in patients with obesity and HFpEF, with consistent benefits regardless of baseline LVEF.
Abstract
BACKGROUND: Many therapies for heart failure (HF) have shown differential impact across the spectrum of left ventricular ejection fraction (LVEF). OBJECTIVES: In this prespecified analysis, the authors assessed the effects of semaglutide across the baseline LVEF strata in patients with the obesity phenotype of HF with preserved ejection fraction (HFpEF) in the STEP-HFpEF (Semaglutide Treatment Effect in People with obesity and HFpEF) trial. METHODS: STEP-HFpEF randomized 529 patients (263 semaglutide; 266 placebo). For this prespecified analysis, patients were categorized into 3 groups based on LVEF: 45% to 49% (n = 85), 50% to 59% (n = 215), and ≥60% (n = 229). RESULTS: At 52 weeks, semaglutide improved the dual primary endpoints of Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (estimated treatment difference: EF ejection fraction 45%-49%: 5.0 points 95% CI: -2.7 to 12.8 points, EF 50%-59%: 9.8 points 95% CI: 5.0 to 14.6 points, and EF ≥60%: 7.4 points 95% CI: 2.8 to 12.0 points; P interaction = 0.56) and body weight (EF: 45%-49%: -7.6 95% CI: -10.7 to -4.4, EF 50%-59%: -10.6 95% CI: -12.6 to -8.6 and EF ≥60%: -11.9 95% CI: -13.8 to -9.9; P interaction = 0.08), to a similar extent across LVEF categories. Likewise, LVEF did not influence the benefit of semaglutide on confirmatory secondary endpoints: 6-minute walk distance (P interaction = 0.19), hierarchal composite endpoint (P interaction = 0.43), and high-sensitivity C-reactive protein (P interaction = 0.26); or exploratory endpoint of N-terminal pro-brain natriuretic peptide (P interaction = 0.96). Semaglutide was well-tolerated across LVEF categories. CONCLUSIONS: In patients with HFpEF and obesity, semaglutide 2.4 mg improved symptoms, physical limitations, and exercise function, and reduced inflammation and body weight to a similar extent across LVEF categories. These data support treatment with semaglutide in patients with the obesity phenotype of HFpEF regardless of LVEF. (Research Study to Investigate How Well Semaglutide Works in People Living With Heart Failure and Obesity STEP-HFpEF; NCT04788511).
Cite This Study
Butler et al. (Mon,) conducted a rct in Heart failure with preserved ejection fraction (HFpEF) and obesity (n=529). Semaglutide vs. Placebo was evaluated on Kansas City Cardiomyopathy Questionnaire Clinical Summary Score and body weight. Semaglutide 2.4 mg improved KCCQ Clinical Summary Score and reduced body weight to a similar extent across LVEF categories (45-49%, 50-59%, ≥60%) in patients with HFpEF and obesity.