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.

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.