Comparative efficacy of lipid-lowering therapies on the cardio-renal-metabolic axis in diabetic kidney disease: a Bayesian network meta-analysis addressing residual CRM risk

Background: In diabetic kidney disease (DKD), dyslipidemia accelerates renal decline and heart failure risk, making Cardio-Renal-Metabolic (CRM) risk reduction critical. The bidirectional relationship between cardiac and renal dysfunction further highlights the necessity of lipid-lowering therapy as a common intervention pathway; however, its comparative efficacy remains unclear. Objective: To compare the Cardio-Renal-Metabolic (CRM) outcomes of various lipid-lowering agents. Methods: We searched PubMed, Embase, Web of Science, and Cochrane Library for Randomized Controlled Trials (RCTs) up to May 10, 2025; a Bayesian network meta-analysis compared their effects. Results: From 20 RCTs, Cerivastatin best reduced Total Cholesterol (TC) (Mean Difference (MD): -94.03, 95% CI: -185.37 to -2.16), while Simvastatin best lowered Low-Density Lipoprotein Cholesterol (LDL-C) (MD: -56.05, 95% CI: -101.64 to -11.66). For cardiorenal outcomes, Atorvastatin, Rosuvastatin, and Fenofibrate potentially improved Urine Albumin-to-Creatinine Ratio (UACR). Atorvastatin (MD: -3.19, 95% CI: -5.12 to -1.27) and Fenofibrate (MD: -1.44, 95% CI: -2.78 to -0.09) most robustly reduced cardiovascular event rates (CVER) in hyperlipidemic DKD. Conclusion: Lipid-lowering agents have divergent effects; Atorvastatin and Fenofibrate best reduce CVER despite variable renal effects, supporting a phenotype-driven CRM strategy prioritizing residual cardiovascular risk reduction. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/view/, identifier CRD420251049719.