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 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 m2/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.…
How strong is the evidence?
Evidence Hub reads this as a meta-analysis, done in people. Its evidence level is 1 of 5 (Highest · pooled evidence). Pooled evidence from several studies sits at the top of the evidence pyramid. Reported size: 1,000 participants or records.
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