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GLP-1RA versus placebo in patients with heart failure and mildly reduced or preserved ejection fraction: An updated

Sanchit Duhan1, Krishna Kurpad1, Bijeta Keisham2

  • 1Department of Cardiology, Carle Foundation Hospital, University of Illinois Urbana-Champaign, IL, USA.

International Journal of Cardiology
|July 7, 2025
PubMed

Insights

Glucagon-like peptide-1 receptor agonists (GLP-1RA) significantly reduce heart failure (HF) exacerbations and improve patient function, but do not show an overall mortality benefit in HF with preserved and mildly reduced ejection fraction. These findings suggest GLP-1RA can help reduce hospitalizations and the healthcare burden of HF.

Area of Science:

  • Cardiology
  • Endocrinology
  • Pharmacology

Background:

  • Limited effective therapies exist for heart failure (HF) with preserved and mildly reduced ejection fraction (EF).
  • Overweight, obese, and diabetic individuals with HF face heightened risks of hospitalization and mortality.
  • Glucagon-like peptide-1 receptor agonists (GLP-1RA) are emerging as potential therapeutic agents in cardiovascular disease.

Purpose of the Study:

  • To evaluate the efficacy and safety of GLP-1RA in patients with HF and preserved or mildly reduced EF.
  • To assess the impact of GLP-1RA on cardiovascular mortality, HF exacerbations, functional status, and body weight.

Main Methods:

  • A systematic review and meta-analysis of randomized controlled trials involving HF patients treated with GLP-1RA (semaglutide, tirzepatide) or placebo.
  • Searches were conducted in Cochrane, Embase, and MEDLINE databases up to November 2024.
  • Outcomes included adverse cardiovascular events, mortality, HF hospitalizations, quality of life (Kansas City Cardiomyopathy Questionnaire), 6-minute walk distance, and body weight.

Main Results:

  • 4474 patients with HF (preserved/mildly reduced EF) were analyzed; 50.91% received GLP-1RA.
  • GLP-1RA significantly reduced the composite of cardiovascular mortality and worsening HF exacerbation (RR: 0.64).
  • HF exacerbations were significantly reduced (RR: 0.59), quality of life improved (SMD: 7.38), 6-minute walk distance increased (SMD: 17.69), and body weight decreased (SMD: -9.56) with GLP-1RA. No significant difference in cardiovascular deaths was observed.
  • Subgroup analysis revealed no significant reduction in cardiovascular deaths (RR: 0.89).

Conclusions:

  • GLP-1RA effectively reduce heart failure exacerbations and hospitalizations in patients with preserved and mildly reduced EF.
  • These agents improve functional status and quality of life, contributing to a reduced global healthcare burden of HF.
  • While GLP-1RA demonstrate significant benefits in HF exacerbations and functional status, current data do not support an overall mortality benefit.
Abstract

Keywords:
GLP-1 receptor agonistHeart failureMeta-analysisRandomized controlled trials

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