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 peptide 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/1.73 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).

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.