Cardiovascular Efficacy of <scp>GLP</scp> ‐1 Receptor Agonists by Kidney Function: An Updated Meta‐Analysis of Randomized Trials Including the <scp>SOUL</scp> Trial

ABSTRACT Aims To evaluate the cardiovascular efficacy and absolute benefit of glucagon‐like peptide‐1 receptor agonists (GLP‐1RAs) by baseline estimated glomerular filtration rate (eGFR). Materials and Methods 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 &lt; 60 and ≥ 60 mL/min/1.73 m 2 . Random‐effects meta‐analyses estimated pooled HRs within each eGFR stratum and the pooled ratio of HRs (RHR) comparing eGFR &lt; 60 versus ≥ 60 mL/min/1.73 m 2 . Exploratory absolute risk reduction (ARR) and number needed to treat (NNT) were derived from placebo‐group MACE risk and the corresponding pooled HR. Results 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 &lt; 60 mL/min/1.73 m 2 , with pooled HRs of 0.83 (95% CI 0.77–0.90; p &lt; 0.001; I 2 = 35.6%) and 0.83 (95% CI 0.74–0.93; p &lt; 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 &lt; 60 than ≥ 60 mL/min/1.73 m 2 (2.6% vs. 1.6%), corresponding to NNTs of 39 (95% CI 26–91) versus 62 (95% CI 46–101). Conclusions 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.