Comparative Efficacy and Safety of Cardio-Renoprotective Pharmacological Interventions in Chronic Kidney Disease: An Umbrella Review of Network Meta-Analyses and a Multicriteria Decision Analysis

Abstract

Sodium-glucose co-transporter 2 inhibitors (SGLT2i), glucagon-like peptide-1 receptor agonists (GLP1a), and non-steroidal mineralocorticoid receptor antagonists (ns-MRA) are promising treatments for chronic kidney disease. This umbrella review of network meta-analyses evaluated their effects on cardiovascular outcomes, kidney disease progression, and adverse events, using the TOPSIS method to identify the optimal intervention based on P-scores. A total of 19 network meta-analyses and 44 randomized controlled trials involving 86,150 chronic kidney disease patients were included. Compared to placebo, SGLT2i were associated with reduced risks of cardiovascular events [Hazard ratio (HR): 0.776, 95% confidence intervals (CI): 0.727–0.998], kidney disease progression (HR: 0.679, 95% CI: 0.629–0.733), acute kidney injury (HR: 0.873, 95% CI: 0.773–0.907), and serious adverse events (HR: 0.881, 95% CI: 0.847–0.916). GLP1a and ns-MRA were also associated with significant reductions in cardiovascular and kidney-specific composite outcomes. Indirect evidence showed that SGLT2i demonstrated a lower risk of kidney disease progression compared to GLP1a (HR: 0.826, 95% CI: 0.716–0.952) and ns-MRA (HR: 0.818, 95% CI: 0.673–0.995), representing the best intervention across all endpoints. In conclusion, while SGLT2i, GLP1a, and ns-MRA all reduce cardiovascular and kidney disease risks in chronic kidney disease, SGLT2i appears to provide the most favorable balance of efficacy and safety.