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 m². 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.