Evaluation of Modification of Diet in Renal Disease study and Cockcroft-Gault equations for sitagliptin dosing

Abstract

Assessment of kidney function is necessary to determine appropriate dosing regimens. While the Cockcroft-Gault (CG) equation is used to calculate the estimated creatinine clearance (eCLCr) for drug dosing, the Modification of Diet in Renal Disease (MDRD) Study equation has recently been advocated. Sitagliptin is a dipeptidyl-peptidase IV inhibitor with dose adjustments based on eCLCr. We assessed discordance in sitagliptin doses recommended using MDRD and CG equations. Adult patients with type 2 diabetes mellitus were included. Estimated glomerular filtration rate (eGFR) individualized for body surface area (eGFR-BSA) and eCLCr were calculated by the MDRD and CG equations, respectively, and sitagliptin dose was determined. Discordance in doses recommended by method were compared overall and by subgroup based on eCLCr category. A total of 121 patients were included: 52% male, 90% white, mean age 61 ± 12 years, weight 93 ± 19 kg, BSA 2.0 ± 0.22 m2 and body mass index (BMI; calculated as kg/m2) 33 ± 7. Mean eGFR-BSA was 76 ± 19 ml/min and eCLCr was 68 ± 17 ml/min. Discordance in sitagliptin dose was observed in 11 patients (9%) with MDRD compared with CG. All patients with eCLCr =50 would have received a higher dose using MDRD, while patients with eCLCr >50 would have received a lower dose. Overall there was agreement in sitagliptin dose using MDRD and CG equations. Discrepancies resulted in underestimation of sitagliptin dose at eCLCr above 50 ml/min and overestimation at lower eCLCr. Clinical implications are the potential for excessive dosing of sitagliptin and other agents with similar dose stratification by eCLCr in individuals with kidney dysfunction.