In the STEP-HFpEF program, semaglutide 2.4 mg produced greater weight loss in women (-9.6% vs -7.2%, P interaction=0.006) but improved heart failure symptoms, physical limitations, and exercise function equally in both sexes.
-9.6% vs -7.2% weight lossWomen lost more weight than men on semaglutide, but heart failure symptom improvements were equal
What the researchers found
Semaglutide 2.4 mg produced greater weight loss in women vs men (-9.6% vs -7.2%, P interaction=0.006) but equivalent HF symptom improvements (KCCQ-CSS ~+7.5 points) in obesity-related HFpEF.
Why it matters
More women than men have HFpEF, and sex-based differences in treatment response are poorly studied. This analysis confirms that semaglutide is effective for both sexes — and that women may derive even greater metabolic benefit from the weight loss component.
The numbers in context
More women than men in the study population; semaglutide 2.4 mg weekly; consistent treatment effects across sexes.
How the study worked
Prespecified secondary analysis of pooled STEP-HFpEF and STEP-HFpEF DM randomized trials. 1,145 patients (49.7% women) with HFpEF and BMI ≥30, randomized to semaglutide 2.4 mg vs placebo for 52 weeks, stratified by sex.
Who was studied
Men and women with obesity-related HFpEF
What this study cannot tell us
Subgroup analysis — not independently powered for sex differences. Baseline differences between sexes may confound comparisons. The greater weight loss in women doesn't appear to translate to greater symptom improvement, raising questions about what mediates symptom benefit.
How to read the evidence
Strong evidence — prespecified secondary analysis of two large randomized trials with near-equal sex enrollment.
When this study was published
Published in 2024. Part of the STEP-HFpEF program with sex-specific analysis reflecting modern trial design standards.
The bigger picture
Sex-specific analysis of major heart failure trials is essential because women have historically been underrepresented in cardiovascular research. STEP-HFpEF's near-equal enrollment and prespecified sex analysis sets a standard for inclusive cardiovascular trial design.
Questions still open
- Why does greater weight loss in women not translate to greater symptom improvement?
- Are the mechanisms of semaglutide's HF benefit partially independent of weight loss?
- Should weight loss targets differ by sex in obesity-related HFpEF management?
Common questions
Does semaglutide work differently for men and women with heart failure?
Should women with heart failure and obesity consider semaglutide?
Read the original research
Efficacy of Semaglutide by Sex in Obesity-Related Heart Failure With Preserved Ejection Fraction: STEP-HFpEF Trials.
Journal of the American College of Cardiology, 84(9), 773-785
Citation
Verma, Subodh; Butler, Javed; Borlaug, Barry A; Davies, Melanie; Kitzman, Dalane W; Shah, Sanjiv J; Petrie, Mark C; Barros, Eric; Rönnbäck, Cecilia; Vestergaard, Lene Sommer; Schou, Morten; Ezekowitz, Justin A; Sharma, Kavita; Patel, Shachi; Chinnakondepalli, Khaja M; Kosiborod, Mikhail N. (2024). Efficacy of Semaglutide by Sex in Obesity-Related Heart Failure With Preserved Ejection Fraction: STEP-HFpEF Trials.. Journal of the American College of Cardiology, 84(9), 773-785. https://doi.org/10.1016/j.jacc.2024.06.001