Kidney and Cardiovascular Outcomes Among Patients With CKD Receiving GLP-1 Receptor Agonists: A Systematic Review and Meta-analysis of Randomized Trials

Background and Objective Chronic kidney disease (CKD), especially diabetic kidney disease, remains a major global health burden and is strongly linked to increased cardiovascular risk. Although standard care can slow disease progression, substantial residual risks of kidney decline, cardiovascular events, and death still remain. GLP-1 receptor agonists have shown cardio-kidney benefits in broader diabetes populations, but their efficacy in patients with already reduced kidney function (baseline eGFR < 60 mL/min/1.73 m2) has been uncertain. This study aimed to systematically evaluate kidney, cardiovascular, and survival-related outcomes of GLP-1 receptor agonists in patients with CKD. Its importance lies in directly addressing a high-risk subgroup (baseline eGFR < 60 mL/min/1.73 m2) in which prior evidence has been fragmented and clinical decision-making has often relied on indirect inference.   Methods Randomized controlled trials were searched through May 25, 2024, across major databases. Eligible studies included adults with baseline eGFR < 60 mL/min/1.73 m2 and compared GLP-1 receptor agonists versus control treatment. The main outcomes were: - composite kidney outcomes, - all-cause mortality, - composite cardiovascular outcomes. Twelve RCTs were included, comprising 17,996 participants with baseline eGFR < 60. Pooled effects were estimated using random-effects models and reported as odds ratios (ORs) with 95% confidence intervals. An additional methodological contribution was the harmonized outcome framework: heterogeneous kidney-event definitions across trials were integrated into a comparable composite kidney outcome, with standardized secondary thresholds of eGFR decline (>30%, >40%, and >50%). Key Findings Compared with control treatment, GLP-1 receptor agonists were associated with: lower risk of composite kidney outcomes: OR 0.85 (95% CI 0.77-0.94; P = 0.001), lower risk of significant eGFR decline: decline greater than 30%: OR 0.78 (P = 0.004), decline greater than 40%: OR 0.76 (P = 0.01), decline greater than 50%: OR 0.72 (P < 0.001), lower all-cause mortality: OR 0.77 (95% CI 0.60-0.98; P = 0.03), lower composite cardiovascular outcomes: OR 0.86 (95% CI 0.74-0.99; P = 0.03). Sensitivity analyses suggested larger effect sizes when analyses were restricted to human GLP-1 backbone agents; however, this should be interpreted with caution in view of between-trial differences.   Clinical Relevance This meta-analysis helps address an evidence gap in patients with reduced kidney function. The findings suggest that GLP-1 receptor agonists are associated with lower risks of adverse kidney outcomes, cardiovascular events, and all-cause mortality in CKD populations. By integrating randomized evidence across kidney, cardiovascular, and survival domains, the study provides clinically meaningful, multi-dimensional risk estimates for a population with substantial unmet need. From a clinical perspective, these results support consideration of integrated cardio-kidney risk management in high-risk CKD patients and may inform multidisciplinary care prioritization and future guideline refinement. In particular, the harmonized kidney outcome definitions improve cross-trial interpretability and practical risk communication. More importantly, this work moves beyond asking whether treatment benefit exists; it provides a usable interpretive framework for clinical practice. By aligning heterogeneous trial outcomes into a common kidney-event language and standardized eGFR-decline thresholds, the study strengthens comparability across trials and facilitates translation of evidence into bedside risk discussions and treatment sequencing. Overall, this study provides consolidated and clinically translatable evidence that GLP-1 receptor agonists are associated with more favorable kidney, cardiovascular, and survival outcomes in patients with CKD.   (Provided by: National Taiwan University Hospital research team)