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Semaglutide in Patients with Heart Failure with Preserved Ejection Fraction and Obesity
STEP-HFpEF randomized 529 patients with HFpEF and BMI ≥30 to weekly semaglutide 2.4 mg versus placebo for 52 weeks, showing larger gains in the Kansas City Cardiomyopathy Questionnaire clinical summary score, greater weight loss, and greater improvement in 6-minute walk distance versus placebo.
Design
- n = 529; 1:1 to semaglutide 2.4 mg weekly vs placebo for 52 weeks
- Inclusion: HFpEF + BMI ≥30
- Dual primary endpoints: Δ KCCQ-CSS (symptoms/physical limitations) and % body-weight change
- Confirmatory secondary endpoints: included Δ 6-minute walk distance and a hierarchical win-ratio composite
Principal published contrasts (semaglutide vs placebo)
- KCCQ-CSS: +16.6 vs +8.7 points; estimated difference +7.8 (95% CI 4.8 to 10.9; P < 0.001)
- Body weight (% change): −13.3% vs −2.6%; estimated difference −10.7 percentage points (95% CI −11.9 to −9.4; P < 0.001)
- 6-minute walk distance: +21.5 m vs +1.2 m; estimated difference +20.3 m (95% CI 8.6 to 32.1; P < 0.001)
- Hierarchical composite: win ratio 1.72 (95% CI 1.37 to 2.15; P < 0.001)
- CRP: −43.5% vs −7.3%; estimated treatment ratio 0.61 (95% CI 0.51 to 0.72; P < 0.001)
Safety note
- Serious adverse events 13.3% vs 26.7% in the primary publication’s safety snapshot—interpret with trial-specific definitions and sponsor oversight.
Publication
Kosiborod MN, Abildstrøm SZ, Borlaug BA, et al. N Engl J Med. 2023 Sep 7;389(12):1069–1084. PMID 37622681.
Outcomes
- Dual primary endpoints met: KCCQ-CSS +16.6 vs +8.7 (estimated difference +7.8 points; 95% CI 4.8–10.9; P<0.001); body weight −13.3% vs −2.6% (difference −10.7 percentage points; 95% CI −11.9 to −9.4; P<0.001).
- 6-minute walk distance +21.5 m vs +1.2 m (estimated difference +20.3 m; 95% CI 8.6–32.1; P<0.001); hierarchical composite win ratio 1.72 (95% CI 1.37–2.15; P<0.001).