Outcomes for Inappropriate Renal Dose Adjustment of Dipeptidyl Peptidase-4 Inhibitors in Patients With Type 2 Diabetes Mellitus: Population-Based Study

Objectives: To estimate inappropriate dosing of dipeptidyl peptidase-4 (DPP-4) inhibitors and to assess the risk of emergency department visits, hypoglycemia, and mortality in patients with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD) prescribed inappropriate DPP-4 inhibitor doses because limited real-world information is available regarding rates of DPP-4 inhibitor dose adjustment and its safety in patients with T2DM and CKD. Patients and Methods: We performed a retrospective observational cohort study of 82,332 patients aged 30 to 75 years with T2DM and CKD being treated with DPP-4 inhibitors from January 1, 2012, through December 31, 2014, using the Korean National Health Information Database. We divided the patients according to the prescription of DPP-4 inhibitor with or without dose adjustment according to estimated glomerular filtration rate. The incidences of emergency department visits, hypoglycemia, and mortality were assessed using hazard ratios estimated using Cox proportional hazards regression modeling. Results: Approximately 40% of patients with T2DM and CKD were prescribed an inappropriate dose of DPP-4 inhibitor from 2009 through 2011; this proportion decreased to 24.4% in 2015. Hazard ratios (95% CIs) for inappropriate vs appropriate dosing of DPP-4 inhibitors were 1.115 (1.005-1.237) for mortality, 1.074 (1.018-1.133) for emergency department visits, and 1.192 (1.054-1.349) for severe hypoglycemia after multivariable adjustment for confounding factors. Conclusion: One of every 3 patients with T2DM and CKD received inappropriate dosing of DPP-4 inhibitor, which was associated with high risk of emergency department visits, severe hypoglycemia, and mortality.