title: Efficacy and tolerability of rosiglitazone and pioglitazone in drug-naïve Japanese patients with type 2 diabetes mellitus: a double-blind, 28 weeks' treatment, comparative study.
abstract: OBJECTIVE
  A 28-week, randomized, placebo-controlled study was performed to evaluate efficacy and tolerability of rosiglitazone in Japanese type 2 diabetes patients.
  
  
  METHODS
  373 patients were randomized to rosiglitazone (4-8 mg/day), pioglitazone (15-45 mg/day) or placebo. Agents were titrated to maximum doses at fixed time points in a pre-defined manner. Primary endpoints were superiority of each active treatment compared to placebo in HbA(1c) at week 16, and non-inferiority between active agents in HbA(1c) at week 28, based on a -0.45% margin.
  
  
  RESULTS
  At week 16, improvements versus placebo were observed with rosiglitazone 4 mg/day (-0.96%, p < 0.001) and pioglitazone 30 mg/day (-1.26%, p < 0.001). At week 28, rosiglitazone and pioglitazone were associated with significant changes from baseline of -0.94% and -1.35%, respectively and rosiglitazone produced statistically and clinically significant improvement versus placebo (-1.29%, CI: -1.62, -0.97). Pioglitazone also showed significant improvement versus placebo (-1.64%, CI: -1.96, -1.31). Non-inferiority of rosiglitazone (4-8 mg/day) to pioglitazone (30-45 mg/day) was not demonstrated (treatment-difference: -0.41%, 95% CI: -0.64, -0.18). More patients treated with pioglitazone were withdrawn from the study by adverse events compared with rosiglitazone (14 vs. 4, p = 0.015). Pioglitazone was associated with higher incidences of adverse events relating to edema and weight gain compared with rosiglitazone (edema: 25.2 vs. 11.3%, weight gain: 9.4 vs. 4.4%). There were no reports of ischemic heart disease or congestive heart failure in any treatment group.
  
  
  CONCLUSIONS
  Although non-inferiority to pioglitazone up to 45 mg in efficacy was not shown, rosiglitazone was confirmed to have clinically meaningful efficacy over placebo and fewer fluid-related events than pioglitazone. The study is registered on ClinicalTrials.gov as protocol NCT00297063.
authors.affiliation: The Institute for Adult Diseases, Asahi Life Foundation, Tokyo, Japan.
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Kikuchi
authors.forename: Kohei
authors.initials: K
authors.lastname: Kaku
authors.forename: Masato
authors.initials: M
authors.lastname: Odawara
authors.forename: Shin-ichi
authors.initials: S
authors.lastname: Momomura
authors.forename: Ryutaro
authors.initials: R
authors.lastname: Ishii
mesh_terms: D000328:Adult; D017668:Age of Onset; D000368:Aged; D000465:Algorithms; D044466:Asian People; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000453:epidemiology / Q000208:ethnology; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D000077205:Pioglitazone; D010919:Placebos; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000009:adverse effects* / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D007004:Hypoglycemic Agents; D010919:Placebos; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D000077205:Pioglitazone