The effect of GLP-1 receptor agonists on cardiac remodeling in heart failure patients with preserved and reduced ejection fraction: a systematic review and meta-analysis

May 21, 2025Heart failure reviews

GLP-1 receptor agonists and their impact on heart structure changes in heart failure with preserved or reduced pumping ability

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Abstract

GLP-1 receptor agonists significantly reduced left ventricular mass by 8.6 g in patients with heart failure with preserved ejection fraction (HFpEF).

In HFpEF patients, GLP-1 receptor agonists also reduced left atrial volume by 5.4 ml and lowered NT-proBNP levels.
A decrease in left atrial volume was observed in the heart failure with reduced ejection fraction (HFrEF) population.
No significant improvements were noted in left ventricular ejection fraction, end-diastolic volume, end-systolic volume, or global longitudinal strain.
Significant differences were found between HFpEF and HFrEF regarding end-diastolic and end-systolic volumes.
The results suggest that GLP-1 receptor agonists may offer specific benefits in structural remodeling for HFpEF compared to HFrEF.

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BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1RA) have shown promising effects on heart failure (HF) outcomes, particularly in phenotype-specific populations. However, their impact on cardiac structure and function in HF with preserved ejection fraction (HFpEF) and reduced ejection fraction (HFrEF) remains unclear.

METHODS: Medline, Cochrane Library, and Scopus were queried through December 2024 for primary and secondary analyses of randomized controlled trials comparing GLP-1RA with placebo in HF patients. Outcomes included changes in left ventricular ejection fraction (LVEF), end-diastolic volume (LVEDV), end-systolic volume (LVESV), global longitudinal strain (GLS), left ventricular mass, left atrial volume (LAV), and NT-proBNP levels. Random-effects models were used to calculate weighted mean differences (WMDs) or hazard ratios (HRs).

RESULTS: Six trials (n = 1,195) were included, with three each evaluating HFpEF and HFrEF populations. In patients with HFpEF, GLP-1RA significantly reduced the LV mass (WMD: -8.6 g; 95% CI: -14.6, -2.6; p = 0.005) and LAV (WMD: -5.4 ml; 95% CI: -8.8, -2.0; p = 0.002) and lowered NT-proBNP concentration throughout (HR: 0.85; 95% CI: 0.8, 0.9; p < 0.001). A decrease in LAV was observed in the HFrEF population (WMD: -5.4 ml [95% CI: -8.8, -2.0]; p = 0.002). However, no significant improvements were observed in LVEF, LVEDV, LVESV, or GLS. There were significant differences between HFpEF and HFrEF for LVEDV (p = 0.01) and LVESV (p = 0.04).

CONCLUSIONS: GLP-1RA demonstrated phenotype-specific benefits, improving structural remodeling in HFpEF but showing limited effects in HFrEF. These findings highlight the importance of targeted therapeutic strategies based on HF phenotypes. Further research is warranted to elucidate underlying mechanisms and optimize patient selection.

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The effect of GLP-1 receptor agonists on cardiac remodeling in heart failure patients with preserved and reduced ejection fraction: a systematic review and meta-analysis

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