Estimated Glomerular Filtration Rate Change and Heart Failure Events With GLP ‐1 Receptor Agonists: A Meta‐Analysis and Meta‐Regression of Randomised Controlled Trials

ABSTRACT Aims To examine whether on‐treatment changes in kidney function and cardiometabolic markers are associated with the magnitude of heart failure (HF) risk reduction across large‐scale trials of glucagon‐like peptide‐1 receptor agonists (GLP‐1RAs). Materials and Methods We searched PubMed and Embase from inception to 29 January 2026 for randomised, placebo‐controlled GLP‐1RA trials enrolling ≥ 1000 adults with type 2 diabetes and/or overweight or obesity and a follow‐up of at least one year. The primary outcome was clinical HF events (hospitalisation for HF, with or without urgent HF visits). We pooled hazard ratios (HRs) using random‐effects meta‐analysis and performed mixed‐effects meta‐regression to test whether between‐group changes in annualised estimated glomerular filtration rate (eGFR) improvement, body weight, systolic blood pressure (SBP), and heart rate were associated with the treatment effect on clinical HF events. Results Eleven trials were included (90 867 participants; 2863 clinical HF events). GLP‐1RAs reduced the risk of clinical HF events (HR 0.86, 95% CI 0.80 to 0.93, p < 0.001, I 2 = 2.1%). In meta‐regression, annualised eGFR improvement was significantly associated with greater HF risk reduction ( p = 0.009); at the trial level, each 1 mL/min/1.73 m 2 /year greater improvement in eGFR corresponded to a 21% lower hazard of clinical HF events (95% CI 7% to 32%). In contrast, changes in body weight, SBP, and heart rate were not associated with HF risk reduction. Conclusions Across large‐scale GLP‐1RA trials, greater annualised eGFR improvement was associated with larger reductions in clinical HF events. Annualised eGFR change may serve as a useful marker of HF benefit with GLP‐1RAs.