PMID-39181597 — SELECT Prespecified HF Subgroup (Lancet 2024)

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

Citation

Kosiborod MN, Deanfield J, Pratley R, Borlaug BA, Butler J, Davies MJ, Emerson SS, Kahn SE, Kitzman DW, Lingvay I, Mahaffey KW, Patel MR, Petrie MC, Plutzky J, Rasmussen S, Ryan DH, Sattar N, Shah SJ, Verma S, Weeke PE, Lincoff AM; SELECT Trial Committees and Investigators. Semaglutide and cardiovascular outcomes in patients with obesity and prevalent heart failure: a prespecified analysis of the SELECT trial. Lancet. 2024;404(10454):773-786. doi: 10.1016/S0140-6736(24)01498-3. PMID: 39181597.

External URL: PubMed

Study Design

Design: Prespecified subgroup analysis of the SELECT trial
Parent trial: SELECT — semaglutide 2.4 mg vs placebo in 17,604 adults with overweight/obesity + established CVD, without T2D
Subgroup: Participants with investigator-defined HF at enrollment
N: 4,286 participants with HF (24.3% of SELECT cohort)
- HFpEF: 2,273 (53.0%)
- HFrEF: 1,347 (31.4%)
- Unclassified HF: 666 (15.5%)

Key Findings

Semaglutide improved all outcome measures in patients with HF compared with those without HF — consistent treatment effect regardless of baseline HF status.
Cardiovascular benefits preserved across HF subtypes:
- HFpEF subgroup: consistent with primary SELECT result
- HFrEF subgroup: consistent with primary SELECT result
- Unclassified HF: consistent
Serious adverse events: Less frequent with semaglutide vs placebo, regardless of HF subtype
Importantly: No subgroup-by-treatment interaction detected — benefit is robust across HF phenotypes

Clinical Relevance

This SELECT HF prespecified subgroup is the predecessor and complement to the pooled 4-trial HF analysis (PMID: 39222642). Core teaching points:

Benefits extend to HFrEF — STEP-HFpEF and STEP-HFpEF DM focus specifically on HFpEF; this SELECT subgroup adds HFrEF to the evidence base.
Robust cross-subtype benefit — supports using semaglutide in HF with or without obesity comorbidity.
Foundational for the Kosiborod 4-trial pooled analysis — demonstrates that the SELECT participants with HF were an important contributor to the larger pooled effect size.

Linked Peptides

Semaglutide

Related Lessons

Lesson 5.2 — Semaglutide Deep Dive (HF evidence base)
Lesson 5.4 — Class-level HF context

Related Studies

PMID-37952131 – SELECT Cardiovascular Outcomes Trial — parent trial
PMID-39222642 – Kosiborod 4-Trial Pooled HF Lancet 2024 — broader pooled HF analysis

PMID-39181597 – SELECT HF Prespecified Subgroup Lancet 2024