Semaglutide 2.4 mg once-weekly will be evaluated against placebo in 1,146 randomized participants with the obesity HFpEF phenotype (median LVEF 57%) to assess changes in KCCQ-CSS and body weight.
RCT (n=1,146)
Does semaglutide 2.4 mg once-weekly improve KCCQ-CSS and body weight at 52 weeks in patients with the obesity HFpEF phenotype?
The STEP-HFpEF program successfully enrolled a highly symptomatic cohort of 1,146 patients with the obesity HFpEF phenotype to evaluate the efficacy of semaglutide 2.4 mg on symptoms, physical limitations, and weight loss.
BACKGROUND: The majority of patients with heart failure with preserved ejection fraction (HFpEF) have the obesity phenotype, but no therapies specifically targeting obesity in HFpEF exist. OBJECTIVES: The aim of this study was to describe the design and baseline characteristics of 2 trials of semaglutide, a glucagon-like peptide-1 receptor agonist, in patients with the obesity HFpEF phenotype: STEP-HFpEF (Semaglutide Treatment Effect in People with obesity and HFpEF; NCT04788511) and STEP-HFpEF DM (Semaglutide Treatment Effect in People with obesity and HFpEF and type 2 diabetes; NCT04916470). METHODS: to once-weekly semaglutide at a dose of 2.4 mg or placebo. Participants were eligible if they had a left ventricular ejection fraction (LVEF) ≥45%; NYHA functional class II to IV; a Kansas City Cardiomyopathy Questionnaire (KCCQ)-Clinical Summary Score (CSS) <90 points; and ≥1 of the following: elevated filling pressures, elevated natriuretic peptides plus structural echocardiographic abnormalities, recent heart failure hospitalization plus ongoing diuretic use, and/or structural abnormalities. The dual primary endpoints are the 52-week change in the KCCQ-CSS and body weight. RESULTS: ) with typical features of HFpEF (median LVEF of 57%, frequent comorbidities, and elevated natriuretic peptides). Most participants received diuretic agents and renin-angiotensin blockers at baseline, and approximately one-third were on mineralocorticoid receptor antagonists. Sodium-glucose cotransporter-2 inhibitor use was rare in STEP-HFpEF but not in STEP HFpEF DM (32%). Patients in both trials had marked symptomatic and functional impairments (KCCQ-CSS ∼59 points, 6-minute walking distance ∼300 m). CONCLUSIONS: In total, STEP-HFpEF program randomized 1,146 participants with the obesity phenotype of HFpEF and will determine whether semaglutide improves symptoms, physical limitations, and exercise function in addition to weight loss in this vulnerable group.
Kosiborod et al. (2023) conducted an RCT in Obesity phenotype of heart failure with preserved ejection fraction (HFpEF) (n=1,146). Semaglutide vs. Placebo was evaluated on 52-week change in the KCCQ-CSS and body weight. Semaglutide 2.4 mg once-weekly will be evaluated against placebo in 1,146 randomized participants with the obesity HFpEF phenotype (median LVEF 57%) to assess changes in KCCQ-CSS and body weight.
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