In patients with heart failure with preserved ejection fraction (HFpEF) and obesity, semaglutide 2.4 mg improved symptoms, physical limitations, exercise function and reduced inflammation and body weight to a similar extent across three categories of left ventricular ejection fraction (LVEF), according to an analysis from the STEP-HFpEF study published Oct. 8 in JACC.

Javed Butler, MBBS, FACC, et al., conducted a prespecified analysis to assess the effects of semaglutide across the baseline LVEF strata in patients with the obesity phenotype of HFpEF in the STEP-HFpEF trial.

STEP-HFpEF evaluated the effects of semaglutide 2.4 mg once weekly vs. placebo on symptoms, physical limitations and body weight in 529 patients. For this analysis, patients were categorized into three groups based on LVEF: 45-49% (n=85), 50-59% (n=215) and ≥60% (n=229).

Results from the present analysis showed that at 52 weeks, semaglutide improved the dual primary endpoints of Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS), with an estimated treatment difference of 5.0, 9.8 and 7.4 points for an EF 45-49%, EF 50-59% and EF ≥60%, respectively (p for interaction = 0.56), and body weight, with an estimated treatment difference of –7.6, –10.6 and –11.9%, respectively, (p for interaction = 0.08).

Likewise, LVEF did not influence the benefit of semaglutide on confirmatory secondary endpoints: six-minute walk difference, hierarchal composite endpoint, and C-reactive protein; or the exploratory endpoint of N-terminal pro–B-type natriuretic peptide. Semaglutide was well-tolerated across LVEF categories.

The authors note that STEP-HFpEF was the “first dedicated randomized, controlled trial of GLP-1 receptor agonists in patients with the obesity phenotype of HFpEF,” but that LVEF was not measured in a central laboratory and other related measures were not available, and results “should be interpreted with caution due to variation in patient and trial characteristics.” They write that additional studies should be done to “assess the benefit of semaglutide in patients with the obesity phenotype of HFpEF who have type 2 diabetes.”

In an accompanying editorial comment, Muthiah Vaduganathan, MD, MPH, and John W. Ostrominski, MD, write that “these findings signify an initial paradigm-shifting step toward positioning semaglutide, and possibly other emerging incretin-based therapeutics and weight/metabolismoriented approaches, at the center of obesity-related HFpEF management strategies.”