Supplementary Material for: Cardiovascular and Kidney Outcomes of Glucagon-Like Peptide 1 Receptor Agonist Therapy in Type 2 Diabetes Mellitus and Chronic Kidney Disease: A Systematic Review and Meta-Analysis

Introduction: The effects of glucagon-like receptor 1 receptor agonists (GLP-1 RA) in patients with diabetes and established chronic kidney disease (CKD) remain unclear.
Methods: We systematically searched PubMed, Embase, and Cochrane Library from inception to May 2024 for randomized controlled trials (RCTs) and respective post-hoc studies comparing GLP-1 RAs versus placebo in patients with type 2 diabetes mellitus (T2DM) and established CKD (as per study definition or otherwise defined as having an estimated glomerular filtration rate less than 60 mL/min/1.73m2 and/or urine albumin-to-creatinine ratio more than 30 mg/g). We applied a random-effects model to pool risk ratios (RR), hazard ratios (HR) and 95% confidence intervals (CI).
Results: We included 10 RCTs and post-hoc analyses comprising 18,042 patients, of whom 9,164 (50.8%) were treated with GLP-1 RAs. There were significantly lower rates of major adverse kidney events (RR 0.82; 95% CI 0.74–0.90; p<0.001; high certainty) and a slightly lower incidence of all-cause mortality (HR 0.84; 95% CI 0.71–1.00; p=0.046; moderate certainty) with the use of GLP-1 RAs relative to placebo. This kidney protection remained consistent in patients with stage 3b CKD (RR 0.78; 95% CI 0.65–0.94; p=0.009; high certainty). No significant differences were observed in major adverse cardiovascular events (HR 0.89; 95% CI 0.78–1.02; p=0.090; low certainty) or cardiovascular mortality (HR 0.80; 95% CI 0.60–1.09; p=0.155; very low certainty), possibly due to a lack of statistical power.
Conclusion: GLP-1 RAs were tied to a lower incidence of all-cause mortality and major adverse kidney events in patients with T2DM and established CKD.