Heart failure & cardiomyopathies
Semaglutide and diuretic use in obesity-related heart failure with preserved ejection fraction: a pooled analysis of the STEP-HFpEF and STEP-HFpEF-DM trials
Authors' conclusion
In patients with obesity-related HFpEF, semaglutide improved heart failure-related symptoms and physical limitations across diuretic use subgroups, with more pronounced benefits among patients receiving loop diuretics at baseline. Reductions in weight and improvements in exercise function with semaglutide vs. placebo were consistent in all diuretic use categories. Semaglutide also led to a reduction in loop diuretic use and dose between baseline and 52 weeks.
Study context
- Population
- Patients with obesity-related heart failure with preserved ejection fraction (HFpEF) (BMI ≥ 30 kg/m²)
- Participants
- 1,145 patients
- Comparison
- Semaglutide 2.4 mg once weekly vs placebo, by baseline diuretic use
- Outcome
- Whether efficacy and safety endpoints differed by baseline diuretic use; effect of semaglutide on loop diuretic use and dose
- Follow-up
- 52 weeks
Methodological detailsplacebo-controlled
- Placebo-controlled
Pooled result
As reported in the abstract
Efficacy by baseline diuretic subgroup (no diuretic n = 220; non-loop only n = 223; loop <40 n = 219, 40 n = 309, >40 n = 174 mg/day furosemide equivalents)
Semaglutide vs PlaceboAdjusted mean difference, % (95% CI)
Body weight change, no diuretics
−8.8(−10.3 to −6.3)
Body weight change, highest loop diuretic dose category
−6.9(−9.1 to −4.7)
- KCCQ clinical summary score, on loop diuretics (P for loop vs not on loop)
- adjusted mean difference +9.3 points (95% CI 6.5–12.1); P = 0.042
- KCCQ clinical summary score, not on loop diuretics (P for loop vs not on loop)
- adjusted mean difference +4.7 points (95% CI 1.3–8.2); P = 0.042
- Consistent beneficial effect on body weight across diuretic use categories
- interaction P = .39
- Consistent beneficial effects on all secondary efficacy endpoints (including 6 min walk distance) across diuretic subgroups
- interaction P = .24-.92
Further pooled results
| Outcome | Semaglutide | Placebo | OR (95% CI) | P value | |
|---|---|---|---|---|---|
| Loop diuretic dose change from baseline · 52 weeksLoop diuretic dose reduction | decrease 17% | increase 2.4% | 2.67 (1.70–4.18) | P < 0.001 | |
| Loop diuretic dose change from baseline · 52 weeksLoop diuretic dose increase | 0.35 (0.23–0.53) | P < 0.001 | |||
| 0.20.5125Odds ratio (log scale) |
- Loop diuretic dose change from baseline: dose change between groups P < .0001
Safety
- Safety favoured semaglutide vs placebo across the diuretic subgroups
Original publication
Semaglutide and diuretic use in obesity-related heart failure with preserved ejection fraction: a pooled analysis of the STEP-HFpEF and STEP-HFpEF-DM trials. Eur Heart J. Published 13 May 2024. doi:10.
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