PMID-38599221 — Butler: Pooled STEP-HFpEF + STEP-HFpEF DM (Lancet 2024)

[DRAFT — authored 2026-04-19. Citation verified against PubMed/Lancet 2026-04-19.]

Citation

Butler J, Shah SJ, Petrie MC, Borlaug BA, Abildstrøm SZ, Davies MJ, Hovingh GK, Kitzman DW, Kolkhof P, Lindegaard ML, Merkely B, Verma S, Pfeffer MA, Kosiborod MN; STEP-HFpEF Trial Committees and Investigators. Semaglutide versus placebo in people with obesity-related heart failure with preserved ejection fraction: a pooled analysis of the STEP-HFpEF and STEP-HFpEF DM randomised trials. Lancet. 2024;403(10437):1635-1648. doi: 10.1016/S0140-6736(24)00469-0. PMID: 38599221.

External URL: PubMed

Study Design

Design: Pooled individual-participant analysis of the two STEP-HFpEF trials (STEP-HFpEF + STEP-HFpEF DM)
Population: 1,145 participants with HFpEF + obesity (573 semaglutide, 572 placebo); includes both non-T2D and T2D patients
Primary outcomes examined: KCCQ-CSS, body weight, 6-minute walk distance, CRP, HF events

Key Findings

KCCQ-CSS treatment difference: +7.5 points with semaglutide (P<0.0001)
Body weight difference: −8.4 percentage points with semaglutide (P<0.0001)
6-minute walk distance: +17.1 meters with semaglutide (P<0.0001)
C-reactive protein: Significant reduction with semaglutide (P<0.0001)
Serious adverse events: Lower with semaglutide (n=161) vs placebo (n=301)
Consistency: Benefits maintained across demographic and clinical subgroups (age, sex, baseline KCCQ score, baseline weight, HbA1c)

Clinical Relevance

Butler 2024 pooled analysis consolidates the two STEP-HFpEF trial findings into a single high-power evidence base for semaglutide in obesity-related HFpEF. Key teaching points:

Pooled effect size is robust — KCCQ-CSS +7.5 points across both diabetic and non-diabetic populations.
Cross-trial consistency — Same direction and magnitude of benefit in both populations (though slightly smaller in T2D due to baseline differences).
Better than placebo on primary + secondary endpoints — comprehensive symptom, functional, and metabolic improvement.

Linked Peptides

Semaglutide

Related Lessons

Lesson 5.2 — Semaglutide Deep Dive (HFpEF integrated narrative)
Lesson 5.4 — Class-level HF evidence

Related Studies

PMID-37622681 – STEP-HFpEF Kosiborod Semaglutide HFpEF Obesity — non-T2D parent trial
PMID-38587233 – STEP-HFpEF DM Kosiborod Semaglutide HFpEF T2D — T2D parent trial
PMID-39222642 – Kosiborod 4-Trial Pooled HF Lancet 2024 — broader 4-trial pooled HF analysis

PMID-38599221 – Butler Pooled STEP-HFpEF Lancet 2024