Cardiovascular Efficacy of GLP-1 Receptor Agonists by Kidney Function: An Updated Meta-Analysis of Randomized Trials...

To evaluate the cardiovascular efficacy and absolute benefit of glucagon-like peptide-1 receptor agonists (GLP-1RAs) by baseline estimated glomerular filtration rate (eGFR).

PubMed and EMBASE were searched to 29 April 2026 for randomized placebo-controlled trials of GLP-1RAs in adults with type 2 diabetes or overweight/obesity that reported eGFR-stratified major adverse cardiovascular events (MACE). Hazard ratios (HRs) were extracted for eGFR < 60 and ≥ 60 mL/min/1.73 m². Random-effects meta-analyses estimated pooled HRs within each eGFR stratum and the pooled ratio of HRs (RHR) comparing eGFR < 60 versus ≥ 60 mL/min/1.73 m². Exploratory absolute risk reduction (ARR) and number needed to treat (NNT) were derived from placebo-group MACE risk and the corresponding pooled HR.

Nine publications from eight trials were included, comprising 70 822 participants; 70 534 had eGFR-stratified MACE data. GLP-1RAs similarly reduced MACE risk among participants with eGFR ≥ 60 and < 60 mL/min/1.73 m², with pooled HRs of 0.83 (95% CI 0.77-0.90; p < 0.001; I ² = 35.6%) and 0.83 (95% CI 0.74-0.93; p < 0.001; I ² = 40.9%), respectively. The pooled RHR showed no evidence of effect modification (1.02, 95% CI 0.85-1.21; p = 0.84). ARR was larger with eGFR < 60 than ≥ 60 mL/min/1.73 m² (2.6% vs. 1.6%), corresponding to NNTs of 39 (95% CI 26-91) versus 62 (95% CI 46-101).

GLP-1RAs reduced MACE risk similarly across eGFR strata, while lower eGFR was associated with a larger estimated absolute cardiovascular benefit. These findings support GLP-1RA therapy in individuals with reduced kidney function.