GLP-1 receptor agonists for anthracycline-associated cardiac outcomes: first meta-analytic evaluation in propensity-matched cohorts

Background Anthracyclines are a leading driver of cancer therapy-related cardiac dysfunction and death [1]. Although ESC guidelines recommend ACE inhibitors and β-blockers (Class IIa, Level B), evidence supporting newer cardioprotective agents remains limited [2]. Glucagon-like peptide-1 receptor agonists (GLP-1RA) have shown cardioprotective signals in preclinical models, including attenuation of oxidative stress and preservation of mitochondrial function [3]. However, a focused clinical synthesis in anthracycline-treated populations is lacking. Purpose To evaluate associations between GLP-1RA use and all-cause mortality, heart failure (HF), and cardiovascular (CV) events among cancer patients receiving anthracyclines, providing the first anthracycline-specific meta-analysis of GLP-1RA cardioprotection. Methods In accordance with PRISMA and prospectively registered in PROSPERO, we systematically searched PubMed, Scopus, Embase, and Cochrane from inception through January 2026 for observational studies comparing GLP-1RA with standard care during anthracycline therapy. Two reviewers independently extracted data and assessed risk of bias using ROBINS-I. Meta-analysis was performed in RevMan 5.4.1 using the Generic Inverse Variance method with random-effects models to pool adjusted hazard ratios (HRs) with 95% confidence intervals (CIs). Prespecified outcomes included all-cause mortality, HF events, arrhythmias, and composite CV outcomes. Prespecified subgroup analyses assessed (1) population type (type 2 diabetes-only vs mixed indications) and (2) clinical setting (primary vs secondary prevention). Certainty of evidence was evaluated using GRADE. Results Three propensity-matched cohort studies (n=4,956) were included. GLP-1RA use was associated with lower all-cause mortality (HR 0.70, 95% CI 0.57–0.86; p<0.001; I²=0%) and fewer HF events (HR 0.60, 95% CI 0.46–0.78; p<0.001). Composite CV outcomes were also reduced (HR 0.68, 95% CI 0.56–0.84; p<0.001; I²=0%). No significant effect was observed for atrial fibrillation (HR 1.04, 95% CI 0.81–1.34; p=0.74) or all-cause hospitalization. Subgroup analyses did not identify effect modification by prevention setting or population type (p-interaction>0.5). Evidence certainty was rated as moderate. Conclusion This first anthracycline-specific meta-analysis suggests that GLP-1RA use is associated with lower mortality and HF events in cancer patients receiving anthracyclines. Consistency across prespecified subgroups supports generalizability; prospective randomized trials are required to confirm causality and inform guideline updates.