Use of dipeptidyl peptidase‐4 inhibitors is associated with lower risk of severe renal outcomes in pre‐dialysis patients with Type 2 diabetes

Objectives Patients with diabetes and Stage 5 chronic kidney disease (CKD) not on dialysis are susceptible to renal replacement therapy and severe complications. Among limited antidiabetic options in this vulnerable population, dipeptidyl peptidase‐4 (DPP‐4) inhibitors (DPP‐4i) are widely used; however, supporting evidence is scant. This study assessed severe renal outcomes associated with DPP‐4i in diabetic and pre‐dialysis patients. Methods This study employed an active‐comparator and propensity score–based inverse probability of treatment weighting approach, using Taiwan's nationwide healthcare claims database from 2012 to 2020. We identified patients with diabetes and CKD stage 5 not on dialysis who received erythropoietin (erythropoietin‐stimulating agent), a drug reimbursed for patients with an estimated glomerular filtration rate <15 mL/min/1.73 m 2 . The primary outcome was a composite of renal replacement therapy, renal death, and kidney‐related hospitalization events, and secondary outcomes included each component of the composite and hypoglycemia. Results We included 7271 diabetic and pre‐dialysis patients with CKD stage 5, of whom 5028 received DPP‐4i and 2243 received meglitinides. DPP‐4i were associated with a 14% reduced risk of the renal composite outcome compared to meglitinides (weighted hazard ratio [HR], 0.86; 95% confidence interval, 0.81–0.92). Individual component analysis revealed that the decreased risk was confined to renal replacement therapy, with a 17% reduction. DPP‐4i was related to a 41% decreased severe hypoglycemia risk. Conclusions In diabetic and pre‐dialysis patients with CKD stage 5, DPP‐4i are related to a lower risk of the renal composite outcome, primarily driven by lower renal dialysis risk, and a lower hypoglycemia risk compared with meglitinides.