Association of GLP-1 Receptor Agonist Use With Chronic Kidney Disease Risk in Type 2 Diabetes: Multicenter Emulated Target Trials.

Abstract

To determine whether glucagon-like peptide-1 receptor agonist (GLP-1 RA) initiation is associated with reduction of incident renal outcomes compared with dipeptidyl peptidase-4 inhibitors (DPP-4is) in patients with type 2 diabetes (T2D) without pre-existing chronic kidney disease (CKD). This study identified 370,636 patients with T2D from the TriNetX Collaborative Network database between January 1, 2015, and June 30, 2023. An emulated target trial was constructed, comprising 24,510 propensity score-matched pairs of new users of GLP-1 RAs and DPP-4is. Composite CKD events (defined as a combination of CKD diagnosis, estimated glomerular filtration rate <60 mL/min per 1.73 m², dialysis, and kidney transplantation), acute kidney injury, major adverse cardiac events, and all-cause mortality were compared between two groups using Kaplan-Meier estimates and Cox proportional hazards models. Participants were 57.6±12.0 years of age and 48.9% were male. Compared with DPP-4i users, GLP-1 RA users had significantly reduced risks of composite kidney outcomes (HR, 0.85; 95% CI, 0.82 to 0.87), incident CKD (HR, 0.85; 95% CI, 0.82 to 0.88), dialysis (HR, 0.53; 95% CI, 0.43 to 0.64), acute kidney injury (HR, 0.81; 95% CI, 0.76 to 0.86), major adverse cardiac events (HR, 0.84; 95% CI, 0.81 to 0.88), and all-cause mortality (HR, 0.55; 95% CI, 0.50 to 0.59). Kaplan-Meier analyses confirmed lower cumulative incidence of these outcomes in GLP-1 RA users. Subgroup analyses confirmed consistent benefits across various patient groups. In patients with T2D and no prior CKD, GLP-1 RA use was associated with lower risks of renal complications, incident CKD, cardiovascular events, and death compared with DPP-4is.