Heart failure & cardiomyopathies
Semaglutide and Exercise Function in Obesity-Related Heart Failure with Preserved Ejection Fraction (HFpEF): Insights From the STEP-HFpEF Program
Authors' conclusion
In patients with obesity-related HFpEF, impaired 6MWD is most strongly associated with excess adiposity, congestion, and inflammation. Semaglutide-mediated improvements in HF-related symptoms, physical limitations, and exercise function were consistent across the spectrum of baseline 6MWD, observed as early as 20 weeks after the initiation of treatment, preceding maximal weight loss.
Study context
- Population
- Patients with obesity-related HFpEF
- Participants
- 1,145 patients
- Comparison
- Semaglutide vs placebo
- Primary endpoint
- Change in 6MWD
- Follow-up
- 20 and 52 weeks
Methodological detailspooled, placebo-controlled
- Pooled
- Placebo-controlled
Primary result
As reported in the abstract
6MWD
Semaglutide vs PlaceboTreatment difference, m (95% CI)P value
20 weeks
14.6(8.6–20.7)
P < 0.000152 weeks
17.1(9.2–25.0)
P < 0.0001Further findings
6MWD by subgroup
- Increases in 6MWD similar across all relevant subgroups, no significant interactions
KCCQ-CSS, body weight, C-reactive protein, hierarchical composite, NT-proBNP by tertile of baseline 6MWD
- Semaglutide improved all across the spectrum of baseline 6MWD
- all Pinteraction = NS
6MWD per 1-unit BMI decrease on semaglutide
- Increase in 6MWD per 1-unit BMI decrease
- 4.1 m (95% CI: 2.4-5.7 m; P < 0.0001)
Baseline associates of lower 6MWD
- Lower 6MWD: older, lower KCCQ-CSS, higher BMI and waist circumference, higher C-reactive protein, higher NT-proBNP, more diuretic use
Original publication
Semaglutide and Exercise Function in Obesity-Related HFpEF: Insights From the STEP-HFpEF Program. JACC Heart Fail. Published 3 October 2025. doi:10.
Summarised from the published abstract; every number is checked against it