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Meta-Analysis
. 2025 Jul;31(7):1076-1080.
doi: 10.1016/j.cardfail.2025.01.022. Epub 2025 Feb 22.

Efficacy of GLP-1 Receptor Agonists in Patients With Heart Failure and Mildly Reduced or Preserved Ejection Fraction: A Systematic Review and Meta-Analysis

Saad Ahmed Waqas  1 , Muhammad Umer Sohail  1 , Muhammad Saad  1 , Abdul Mannan Khan Minhas  2 , Stephen J Greene  3 , Marat Fudim  3 , Gregg C Fonarow  4 , Dmitry Abramov  5 , Muhammad Shahzeb Khan  6 , Raheel Ahmed  7
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Free article
Meta-Analysis

Efficacy of GLP-1 Receptor Agonists in Patients With Heart Failure and Mildly Reduced or Preserved Ejection Fraction: A Systematic Review and Meta-Analysis

Saad Ahmed Waqas et al. J Card Fail. 2025 Jul.
Free article

Abstract

Background: Heart failure (HF) with mildly reduced or preserved ejection fraction (HFpEF) accounts for over half of cases of HF, with obesity playing a key role. Residual risk remains high despite available therapies. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have shown potential cardiometabolic benefits, but their role in HFpEF remains unclear.

Methods: A systematic review and meta-analysis of randomized controlled trials evaluating GLP-1RAs in HFpEF were conducted. Studies evaluating GLP-1RA in combination with glucose-dependent insulinotropic polypeptide (GIP) were also included. The analyzed outcomes included cardiovascular (CV) death, worsening HF events and their composite. Hazard ratios (HRs) with 95% confidence intervals (CIs) were pooled by using a random-effects model.

Results: Six randomized controlled trials involving 8788 patients were included. GLP-1RAs significantly reduced the composite outcome of CV death or worsening HF events (HR: 0.68 [0.51-0.89]; P = 0.006, I² = 47%) as well as worsening HF events alone (HR: 0.56 [0.38-0.82]; P = 0.003, I² = 51%). No significant reduction was observed for CV death alone (HR: 0.86 [0.67-1.12]; P = 0.27, I² = 0%).

Conclusion: GLP-1RAs reduce worsening HF events and the composite of CV death or worsening HF in HFpEF, particularly in patients with obesity or diabetes. These findings support their role as a promising therapy requiring further HFpEF-focused trials.

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Conflict of interest statement

Disclosures S.J.G. has received research support from the Duke University Department of Medicine Chair's Research Award, American Heart Association, Amgen, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Cytokinetics, Merck, Novartis, Otsuka, Pfizer, and Sanofi; has served on advisory boards or as consultant for Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Corcept Therapeutics, Corteria Pharmaceuticals, CSL Vifor, Cytokinetics, Eli Lilly, Lexicon, Merck, Novo Nordisk, Otsuka, Roche Diagnostics, Sanofi, scPharmaceuticals, Sumitomo, and Tricog Health; and has received speaker fees from AstraZeneca, Bayer, Boehringer Ingelheim, Cytokinetics, Lexicon, Novo Nordisk, and Roche Diagnostics. M.F. has received research support and consulting fees from Novo Nordisk. G.C.F. reports consulting for Abbott, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Cytokinetics, Eli Lilly, Johnson & Johnson, Medtronic, Merck, Novartis, and Pfizer. D.A. has received speaker fees from Bayer and AstraZeneca. M.S.K. serves on an advisory board for Bayer. All other authors have no conflicts of interest to declare.

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