Heart failure & cardiomyopathies
Frailty and Effects of Semaglutide in Obesity-Related Heart Failure with Preserved Ejection Fraction (HFpEF): Findings From the STEP-HFpEF Program
Authors' conclusion
Semaglutide resulted in a similar reduction in BW across frailty subgroups but greater improvements in HF-related symptoms. Moreover, semaglutide reduced frailty burden after 52 weeks of treatment.
Study context
- Population
- Participants with obesity-related HFpEF, stratified by cumulative deficit-derived frailty index (34 variables): nonfrail, more frail, most frail
- Participants
- 1,145 participants · 2 pooled trials
- Comparison
- Semaglutide 2.4 mg once weekly vs placebo, by baseline frailty status
- Primary endpoint
- Dual primary endpoints: change in KCCQ-CSS and change in body weight
- Follow-up
- 52 weeks
Methodological detailsplacebo-controlled, subgroup analysis by baseline frailty
- Placebo-controlled
- Subgroup analysis by baseline frailty
Primary result
As reported in the abstract
Change in KCCQ-CSS and body weight, by baseline frailty strata
Semaglutide vs PlaceboMean difference (95% CI)
KCCQ-CSS, nonfrail (n=110, 9.6%)
−1.5(−8.4 to 5.4)
KCCQ-CSS, more frail (n=343, 30.0%)
3.7(−0.2 to 7.6)
KCCQ-CSS, most frail (n=692, 60.4%)
11.0(8.1–13.8)
- Semaglutide-mediated weight loss similar across frailty strata
- P for interaction = 0.38
- Kansas City Cardiomyopathy Questionnaire-Clinical Summary Score (KCCQ-CSS) effect varied by frailty status; greatest improvement in most frail
- P for interaction < 0.001
Further findings
| Outcome | OR (95% CI) | P value | |
|---|---|---|---|
| Being nonfrail (frailty burden) · 52 weeks | 3.16 (2.44–4.09) | P < 0.0001 | |
| 0.20.5125Odds ratio (log scale) |
Original publication
Frailty and Effects of Semaglutide in Obesity-Related HFpEF: Findings From the STEP-HFpEF Program. JACC Heart Fail. Published 15 September 2025. doi:10.
Summarised from the published abstract; every number is checked against it