Semaglutide versus placebo in people with obesity-related heart failure with preserved ejection fraction: a pooled analysis of the STEP-HFpEF and STEP-HFpEF DM randomised trials
Key result
Semaglutide improves heart failure symptoms and reduces bodyweight by ~8% versus placebo.
- MD 7.5
- 95% CI 5.3 to 9.8
- P<0.0001
- n=1,145
Why the study?
To provide a more definitive assessment of semaglutide across outcomes and evaluate whether its effects were consistent across key patient subgroups in obesity-related HFpEF.
Does semaglutide improve heart failure-related symptoms, physical limitations, and reduce bodyweight in patients with obesity-related heart failure with preserved ejection fraction?
Population
1145 people with obesity-related HFpEF with or without type 2 diabetes
Comparison
Semaglutide 2.4 mg once weekly vs matched placebo
Design
Prespecified pooled analysis of two randomized, double-blind, placebo-controlled trials
Follow-up
52 weeks
Authors
Discussion
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Implication
In patients with obesity-related HFpEF, semaglutide 2.4 mg weekly significantly improved heart failure symptoms, physical limitations, and body weight compared to placebo, regardless of diabetes status.
Key Points
- This analysis aims to evaluate the efficacy of semaglutide compared to placebo on heart failure symptoms and weight in patients with obesity-related heart failure.
- Conducted a pooled analysis of individual patient data from STEP-HFpEF and STEP-HFpEF DM trials.
- Participants were randomly assigned to 2.4 mg semaglutide or matched placebo for 52 weeks.
- Primary endpoints focused on changes in KCCQ-CSS and bodyweight, with safety assessments for all participants.
- Semaglutide group showed a significantly greater improvement in KCCQ-CSS (mean difference 7.5 points, 95% CI 5.3 to 9.8, p<0.0001) and a reduction in bodyweight (−8.4%, 95% CI −9.2 to −7.5, p<0.0001).
- 6-min walk distance improved by 17.1 meters (95% CI 9.2 to 25.0, p<0.0001), and CRP concentrations were reduced (treatment ratio 0.64, 95% CI 0.56 to 0.72, p<0.0001).
- Semaglutide showed consistent efficacy across multiple demographic and clinical subgroups.
Study Design
Type
RCT (n=1,145)
Blinding
double-blind
Randomization
randomly assigned
Multicenter
Yes
Structured PICO
Does semaglutide improve heart failure-related symptoms, physical limitations, and reduce bodyweight in patients with obesity-related heart failure with preserved ejection fraction?
P
Population
1,145 adults aged ≥18 years with obesity-related heart failure with preserved ejection fraction (LVEF ≥45%, BMI ≥30 kg/m²), followed for 52 weeks.
I
Intervention
Semaglutide 2.4 mg subcutaneously once weekly for 52 weeks (initiated at 0.25 mg weekly and escalated over 16 weeks).
C
Comparator
Matching placebo subcutaneously once weekly for 52 weeks.
O
Outcome
Dual primary endpoints: change from baseline to week 52 in Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS) and percentage change in bodyweight.patient reported
Main Result
Mean Difference: 7.5 (95% CI 5.3–9.8)
p-value: p=<0.0001
In patients with obesity-related HFpEF, semaglutide 2.4 mg weekly significantly improved heart failure symptoms, physical limitations, and body weight compared to placebo, regardless of diabetes status.
Cite This Study
Butler et al. (2024) conducted an RCT in obesity-related heart failure with preserved ejection fraction (n=1,145). Semaglutide vs. matched placebo was evaluated on change from baseline to week 52 in KCCQ-CSS and bodyweight (MD 7.5, 95% CI 5.3 to 9.8, p=<0.0001). Semaglutide was superior to placebo in improving heart failure-related symptoms (mean difference in KCCQ-CSS 7.5 points; P<0.0001) and reducing bodyweight (-8.4%; P<0.0001).