Efficacy of GLP-1 receptor agonists in obese patients with heart failure with preserved ejection fraction: A systematic review and meta-analysis of randomized trials and propensity score-matched cohorts

Oct 31, 2025Current problems in cardiology

GLP-1 receptor drugs' effects in obese patients with a type of heart failure that keeps normal pumping function

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GLP-1 Therapies on OpenScience ↗PubMed ↗DOI ↗

Abstract

GLP-1 receptor agonists significantly reduced heart failure events by 50% in obese patients with preserved ejection fraction.

Treatment with GLP-1 receptor agonists resulted in a 50% reduction in heart failure events compared to placebo.
Improvements were observed in the Kansas City Cardiomyopathy Questionnaire Overall Summary Score, with an increase of 7.38 points.
Participants showed a 17.60 meter increase in Six-minute walk test distance after treatment.
Weight loss of 9.56 kg was associated with the use of GLP-1 receptor agonists.
Trends toward decreased cardiovascular and all-cause mortality were noted, but these findings were not statistically significant.

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BACKGROUND: Heart failure with preserved ejection fraction (HFpEF) remains a major clinical challenge, particularly among obese individuals. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), originally indicated for type 2 diabetes, have demonstrated potential cardiovascular benefits, including weight loss and anti-inflammatory effects. However, their efficacy in HFpEF remains uncertain. We conducted a systematic review and meta-analysis to evaluate the effects of GLP-1 RAs in obese patients with HFpEF.

METHODS: We systematically searched PubMed, Embase, and Cochrane databases for randomized controlled trials (RCTs) and propensity score-matched cohort studies comparing GLP-1 RAs with placebo or standard care in obese HFpEF populations. The primary endpoints of this meta-analysis were as follows: (1) any HF event; (2) Kansas City Cardiomyopathy Questionnaire Overall Summary Score (KCCQ-OSS); and (3) Six-minute walk test (6MWT) distance. A random-effects model was used to pool effect estimates.

RESULTS: Five studies (4 RCTs, 1 propensity-matched cohort) comprising 5,561 patients met inclusion criteria. GLP-1 RAs significantly reduced HF events (HR: 0.50; 95 % CI: 0.36-0.70; p < 0.0001; I² = 29.5 %). Treatment was also associated with improvements in KCCQ-CSS (MD: 7.38 points; 95 % CI: 5.51-9.26; p < 0.0001; I² = 0 %), 6MWT distance (MD: 17.60 m; 95 % CI: 11.86-23.35; p < 0.0001; I² = 0 %) and weight loss (MD: -9.56 kg; 95 % CI: -12.71 to -6.41; p < 0.0001; I² = 95 %). Trends toward reduced CV and all-cause mortality were observed, though not statistically significant.

CONCLUSION: GLP-1 RAs are associated with reductions in HF events and meaningful improvements in quality of life and functional capacity in obese patients with HFpEF. These findings highlight their potential as a therapeutic strategy in this high-risk population.