The effect of GLP-1 receptor agonists on renal outcomes: a systematic review and meta-analysis

Abstract Background and Hypothesis Glucagon-like peptide-1 receptor agonists (GLP1-RAs) are anti-hyperglycaemic agents, with cardioprotective effects, however renal protective effects remain unclear. We aimed to assess the effects of GLP1-RAs on renal outcomes in patients with or without diabetes. Methods We performed a systematic review and meta-analysis with Medline, EMBASE and the Cochrane Register searched to December 2024. The primary outcome was the composite of kidney failure (defined as eGFR 15 mL/min/1.73m2) or dialysis requirement, worsening of renal function and changes in proteinuria. Subgroup analysis was performed based on diabetic status, CKD and individual GLP1-RA drugs. Relative risks (RR) with 95% confidence intervals (CI) for individual trials were pooled using random effects models. Results We identified 19 trials including 90 882 patients. Mean age was 60.8 years and mean follow-up was 25.9 months. GLP1-RAs were associated with a 19% reduction in the risk of primary renal outcome (RR 0.81, 95% CI 0.73–0.89), a 12% reduction in renal functional decline (RR 0.88, 95% CI 0.81–0.95) and a 0.45 ml/min/1.73m2 reduction in yearly loss (16 trials, MD 0.45, 95% CI 0.10–0.81). GLP1-RAs also reduced microalbuminuria by 24% (RR 0.76, 95% CI 0.71–0.82), HbA1c (units: %) by 0.61 (MD -0.61, 95% CI -0.76- -0.49) and body weight by 5 kg (MD -5.24, 95% CI -7.46–-3.02). Although there were no significant differences in progression to kidney failure (RR 0.86, 95% CI 0.71–1.05), GLP1-RAs reduced the incidence of major adverse cardiovascular events (MACE) by 15% (RR 0.85, 95% CI 0.81–0.90) and all-cause mortality by 14% (RR 0.86, 95% CI 0.82–0.91). No significant differences were seen in severe adverse events (RR 0.96, 95% CI 0.90–1.01). However, there were more gastroenterological side effects. Conclusions GLP1-RAs demonstrated cardiovascular and renal benefits. Further high-quality randomised trials assessing their effects in patients without diabetes, with or without proteinuria and/or CKD are needed.