title: Evaluation of the long-term durability and glycemic control of fasting plasma glucose and glycosylated hemoglobin for pioglitazone in Japanese patients with type 2 diabetes.
abstract: BACKGROUND
  This study applied a pharmacodynamic model-based approach to evaluate the long-term durability and glycemic control of pioglitazone in comparison with other oral glucose-lowering drugs in Japanese type 2 diabetes mellitus (T2DM) patients.
  
  
  METHODS
  Japanese T2DM patients were enrolled in a prospective, randomized, open-label, blinded-end point study and received pioglitazone with or without other oral glucose-lowering drugs (excluding another thiazolidinedione [TZD]) (n=293) or oral glucose-lowering drugs excluding TZD (n=294). Treatment was adjusted to achieve glycosylated hemoglobin (HbA1c) <6.9%, and samples for fasting plasma glucose (FPG) and HbA1c were collected over 2.5-4 years. A simultaneous cascading indirect response model structure was applied to describe the time course of FPG and HbA1c. HbA1c levels were described using both an FPG-dependent and an FPG-independent function. To account for titration, drug effects for both treatment groups were implemented using a time-dependent Emax model.
  
  
  RESULTS
  Pioglitazone was superior in both time to maximum effect and the magnitude of reduction achieved in FPG and HbA1c. A greater reduction in median FPG (-21 mg/dL vs. -9 mg/dL) was observed with pioglitazone (P<0.05). Maximum drug effect for FPG was predicted to occur earlier (11 months) for pioglitazone than for the control group (14 months). The simulated additional reduction in FPG and HbA1c achieved with pioglitazone was predicted to be maintained beyond the currently observed study duration.
  
  
  CONCLUSIONS
  Pioglitazone was found to result in improved glycemic control and durability compared with control treatment. This model-based approach enabled the quantification of differences in FPG and HbA1c for both treatment groups and simulation to evaluate longer-term durability on FPG and HbA1c.
authors.affiliation: 1 Model Answers Pty Ltd. , Brisbane, Australia .
authors.forename: Frances
authors.initials: F
authors.lastname: Stringer
authors.forename: Joost
authors.initials: J
authors.lastname: DeJongh
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Enya
authors.forename: Emiko
authors.initials: E
authors.lastname: Koumura
authors.forename: Meindert
authors.initials: M
authors.lastname: Danhof
authors.forename: Kohei
authors.initials: K
authors.lastname: Kaku
mesh_terms: D000328:Adult; D000368:Aged; D044466:Asian People; D001786:Blood Glucose / Q000187:drug effects*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D004359:Drug Therapy, Combination / Q000379:methods; D005215:Fasting / Q000097:blood; D005260:Female; D006442:Glycated Hemoglobin / Q000187:drug effects*; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007564:Japan; D008297:Male; D008875:Middle Aged; D000077205:Pioglitazone; D011446:Prospective Studies; D045162:Thiazolidinediones / Q000627:therapeutic use*; D013995:Time; D016896:Treatment Outcome
chemical_list: D001786:Blood Glucose; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D000077205:Pioglitazone; D045162:Thiazolidinediones; C517652:hemoglobin A1c protein, human