Women Get Greater Weight Loss from Semaglutide for Obesity-Related Heart Failure, but Both Sexes Benefit Equally for Symptoms
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.
Quick Facts
What This Study 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.
Key Numbers
More women than men in the study population; semaglutide 2.4 mg weekly; consistent treatment effects across sexes.
How They Did This
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.
Why This Research 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 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.
What This Study Doesn't 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.
Questions This Raises
- ?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?
Trust & Context
- Key Stat:
- -9.6% vs -7.2% weight loss Women lost more weight than men on semaglutide, but heart failure symptom improvements were equal
- Evidence Grade:
- Strong evidence — prespecified secondary analysis of two large randomized trials with near-equal sex enrollment.
- Study Age:
- Published in 2024. Part of the STEP-HFpEF program with sex-specific analysis reflecting modern trial design standards.
- Original Title:
- Efficacy of Semaglutide by Sex in Obesity-Related Heart Failure With Preserved Ejection Fraction: STEP-HFpEF Trials.
- Published In:
- Journal of the American College of Cardiology, 84(9), 773-785 (2024)
- Authors:
- Verma, Subodh(15), Butler, Javed(16), Borlaug, Barry A(17), 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
- Database ID:
- RPEP-09438
Evidence Hierarchy
Frequently Asked Questions
Does semaglutide work differently for men and women with heart failure?
Both men and women got the same improvement in heart failure symptoms and exercise ability. However, women lost more weight on semaglutide — about 9.6% of body weight compared to 7.2% for men. So both sexes benefit equally for heart failure, but women may see a bigger change on the scale.
Should women with heart failure and obesity consider semaglutide?
Yes — this study of over 1,100 patients showed that semaglutide is safe and effective for both women and men with obesity-related heart failure. Women actually lost more weight than men while getting the same heart failure improvements, making it a strong option for women with this condition.
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Cite This Study
https://rethinkpeptides.com/research/RPEP-09438APA
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
MLA
Verma, Subodh, et al. "Efficacy of Semaglutide by Sex in Obesity-Related Heart Failure With Preserved Ejection Fraction: STEP-HFpEF Trials.." Journal of the American College of Cardiology, 2024. https://doi.org/10.1016/j.jacc.2024.06.001
RethinkPeptides
RethinkPeptides Research Database. "Efficacy of Semaglutide by Sex in Obesity-Related Heart Fail..." RPEP-09438. Retrieved from https://rethinkpeptides.com/research/verma-2024-efficacy-of-semaglutide-by
Access the Original Study
Study data sourced from PubMed, a service of the U.S. National Library of Medicine, National Institutes of Health.
This study breakdown was produced by the RethinkPeptides research team. We analyze and report published research findings without making health recommendations. All interpretations are based solely on the published abstract and study data.