Population pharmacodynamic analysis of hemoglobin A1c-lowering effects by adding treatment of DPP-4 inhibitors (sitagliptin) in type 2 diabetes mellitus patients based on electronic medical records

Abstract

AimTo develop a population pharmacodynamic (PPD) model describing the time course for the hemoglobin A1c (HbA1c)-lowering effects of adding treatment of DPP-4 inhibitors and to assess the efficacy of combination therapy in type 2 diabetes mellitus patients based on electronic medical records. MethodsInformation on patients was collected retrospectively from electronic medical records. Of the 4 DPP-4 inhibitors used, we focused on sitagliptin as it had the best time-response relationships. A physiological indirect response model was developed to describe changes in HbA1c levels. ResultsAn indirect response model, based on the 1300 HbA1c levels of 160 patients, described the time course for the HbA1c-lowering effects of adding sitagliptin. The combination with pioglitazone decreased the HbA1c synthesis rate by 7.74% relative to without pioglitazone. Bayesian forecasting based on the final PDD model using the first two HbA1c observations, before and within 30days after the addition of sitagliptin, gave a precise prediction of HbA1c-lowering effects individually. ConclusionsOur PPD model quantitatively described the beneficial effects of combination therapy with pioglitazone and sitagliptin. The proposal methodology is also expected to be applicable to other medicines based on electronic medical records in clinical practice.