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

The effects of glucagon-like peptide 1 receptor agonists (GLP-1 RA) in patients with diabetes and established chronic kidney disease (CKD) remain unclear. 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/1.73 m2 and/or urine albumin-to-creatinine ratio more than 30 mg/g). We applied a random-effects model to pool risk ratios (RRs), hazard ratios (HRs), and 95% confidence intervals (CIs). 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. 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.