PMID-38587233 — STEP-HFpEF DM: Semaglutide in HFpEF + Obesity + T2D

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

Citation

Kosiborod MN, Petrie MC, Borlaug BA, Butler J, Davies MJ, Hovingh GK, Kitzman DW, Møller DV, Treppendahl MB, Verma S, Jensen TJ, Liisberg K, Lindegaard ML, Abhayaratna W, Ahmed FZ, Ben-Gal T, Chopra V, Ezekowitz JA, Fu M, Ito H, Lelonek M, Melenovský V, Merkely B, Núñez J, Perna E, Schou M, Senni M, Sharma K, van der Meer P, Von Lewinski D, Wolf D, Sattar N; STEP-HFpEF DM Trial Committees and Investigators. Semaglutide in Patients with Obesity-Related Heart Failure and Type 2 Diabetes. N Engl J Med. 2024;390(15):1394-1407. doi: 10.1056/NEJMoa2313917. PMID: 38587233.

External URL: PubMed

Study Design

Design: Double-blind, randomized, placebo-controlled, multicenter Phase 3
Population: Adults with HFpEF (LVEF ≥45%) + obesity (BMI ≥30) + type 2 diabetes
Setting: 108 sites across 16 countries (Asia, Europe, North and South America)
N: 616 participants
Intervention: Semaglutide 2.4 mg weekly SC vs matching placebo; 52 weeks
Dual primary endpoints: Change in KCCQ-CSS and change in body weight

Key Findings

KCCQ-CSS change: Semaglutide +13.7 vs placebo +6.4 (estimated treatment difference +7.3 points, 95% CI 4.1-10.4, P<0.001)
Body weight change: Semaglutide −9.8% vs placebo −3.4% (estimated treatment difference −6.4 pp, 95% CI −7.6 to −5.2, P<0.001)
6-minute walk distance: Significantly improved with semaglutide
Consistency across HbA1c strata: Treatment benefits preserved regardless of baseline HbA1c level
Hypoglycemia: Lower rates on semaglutide than placebo — despite concomitant glucose-lowering medications
Safety: Adverse events comparable; GI events higher with semaglutide as expected

Clinical Relevance

STEP-HFpEF DM extends the STEP-HFpEF finding to T2D population, completing the HFpEF + obesity evidence base across diabetic and non-diabetic phenotypes. Core points:

Treatment effect preserved in T2D — modestly smaller in absolute magnitude than non-T2D STEP-HFpEF (probably because T2D population had less weight-loss "room"), but clinically meaningful.
Hypoglycemia safety — despite glucose-lowering effect, hypoglycemia was lower with semaglutide vs placebo (likely due to glucose-dependent insulin secretion mechanism).
Guideline-level change — ADA/AACE/EASO 2025 and 2026 guidelines now support semaglutide in T2D + obesity + HFpEF based on this evidence.

Linked Peptides

Semaglutide

Related Lessons

Lesson 5.2 — Semaglutide Deep Dive (HFpEF + T2D section)
Lesson 5.4 — Class-level HF evidence

Related Studies

PMID-37622681 – STEP-HFpEF Kosiborod Semaglutide HFpEF Obesity — non-T2D companion
PMID-38599221 – Butler Pooled STEP-HFpEF Lancet 2024 — pooled analysis of STEP-HFpEF + STEP-HFpEF DM
PMID-39222642 – Kosiborod 4-Trial Pooled HF Lancet 2024 — 4-trial pooled HF analysis

PMID-38587233 – STEP-HFpEF DM Kosiborod Semaglutide HFpEF T2D