title: 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: To 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.
  
  
  
  Information 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.
  
  
  
  An 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.
  
  
  
  Our 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.
authors.affiliation: Department of Clinical Pharmacokinetics, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Kakara
authors.affiliation: Department of Clinical Pharmacokinetics, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka 812-8582, Japan; Osaka Headquarters, Tokushukai General Incorporated Association, Osaka 530-0001, Japan; Hospital Pharmacy, Fukuoka Tokushukai Medical Center, Fukuoka 816-0864, Japan.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Nomura
authors.affiliation: Department of Clinical Pharmacokinetics, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
authors.forename: Mai
authors.initials: M
authors.lastname: Ezaki
authors.affiliation: Department of Clinical Pharmacokinetics, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Fukae
authors.affiliation: Department of Clinical Pharmacokinetics, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Hirota
authors.affiliation: Department of Psychosomatic Medicine, Fukuoka Tokushukai Medical Center, Fukuoka 816-0864, Japan.
authors.forename: Sunao
authors.initials: S
authors.lastname: Matsubayashi
authors.affiliation: Hospital Pharmacy, Fukuoka Tokushukai Medical Center, Fukuoka 816-0864, Japan.
authors.forename: Masaaki
authors.initials: M
authors.lastname: Hirakawa
authors.affiliation: Department of Clinical Pharmacokinetics, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka 812-8582, Japan. Electronic address: ieiri-ttr@umin.ac.jp.
authors.forename: Ichiro
authors.initials: I
authors.lastname: Ieiri
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001499:Bayes Theorem; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D057286:Electronic Health Records; D005260:Female; D006442:Glycated Hemoglobin / Q000032:analysis*; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D000068900:Sitagliptin Phosphate / Q000627:therapeutic use*; D013997:Time Factors
chemical_list: D054873:Dipeptidyl-Peptidase IV Inhibitors; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D000068900:Sitagliptin Phosphate
keywords: Electronic medical records; Hemoglobin A1c; Pioglitazone; Population pharmacodynamics; Sitagliptin