title: Pioglitazone for diabetes prevention in impaired glucose tolerance.
abstract: BACKGROUND
  Impaired glucose tolerance is associated with increased rates of cardiovascular disease and conversion to type 2 diabetes mellitus. Interventions that may prevent or delay such occurrences are of great clinical importance.
  
  
  METHODS
  We conducted a randomized, double-blind, placebo-controlled study to examine whether pioglitazone can reduce the risk of type 2 diabetes mellitus in adults with impaired glucose tolerance. A total of 602 patients were randomly assigned to receive pioglitazone or placebo. The median follow-up period was 2.4 years. Fasting glucose was measured quarterly, and oral glucose tolerance tests were performed annually. Conversion to diabetes was confirmed on the basis of the results of repeat testing.
  
  
  RESULTS
  Annual incidence rates for type 2 diabetes mellitus were 2.1% in the pioglitazone group and 7.6% in the placebo group, and the hazard ratio for conversion to diabetes in the pioglitazone group was 0.28 (95% confidence interval, 0.16 to 0.49; P<0.001). Conversion to normal glucose tolerance occurred in 48% of the patients in the pioglitazone group and 28% of those in the placebo group (P<0.001). Treatment with pioglitazone as compared with placebo was associated with significantly reduced levels of fasting glucose (a decrease of 11.7 mg per deciliter vs. 8.1 mg per deciliter [0.7 mmol per liter vs. 0.5 mmol per liter], P<0.001), 2-hour glucose (a decrease of 30.5 mg per deciliter vs. 15.6 mg per deciliter [1.6 mmol per liter vs. 0.9 mmol per liter], P<0.001), and HbA(1c) (a decrease of 0.04 percentage points vs. an increase of 0.20 percentage points, P<0.001). Pioglitazone therapy was also associated with a decrease in diastolic blood pressure (by 2.0 mm Hg vs. 0.0 mm Hg, P=0.03), a reduced rate of carotid intima-media thickening (31.5%, P=0.047), and a greater increase in the level of high-density lipoprotein cholesterol (by 7.35 mg per deciliter vs. 4.5 mg per deciliter [0.4 mmol per liter vs. 0.3 mmol per liter], P=0.008). Weight gain was greater with pioglitazone than with placebo (3.9 kg vs. 0.77 kg, P<0.001), and edema was more frequent (12.9% vs. 6.4%, P=0.007).
  
  
  CONCLUSIONS
  As compared with placebo, pioglitazone reduced the risk of conversion of impaired glucose tolerance to type 2 diabetes mellitus by 72% but was associated with significant weight gain and edema. (Funded by Takeda Pharmaceuticals and others; ClinicalTrials.gov number, NCT00220961.).
authors.affiliation: Texas Diabetes Institute and University of Texas Health Science Center, San Antonio, TX 78229, USA. albarado@uthscsa.edu
authors.forename: Ralph A
authors.initials: RA
authors.lastname: DeFronzo
authors.forename: Devjit
authors.initials: D
authors.lastname: Tripathy
authors.forename: Dawn C
authors.initials: DC
authors.lastname: Schwenke
authors.forename: MaryAnn
authors.initials: M
authors.lastname: Banerji
authors.forename: George A
authors.initials: GA
authors.lastname: Bray
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Buchanan
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Clement
authors.forename: Robert R
authors.initials: RR
authors.lastname: Henry
authors.forename: Howard N
authors.initials: HN
authors.lastname: Hodis
authors.forename: Abbas E
authors.initials: AE
authors.lastname: Kitabchi
authors.forename: Wendy J
authors.initials: WJ
authors.lastname: Mack
authors.forename: Sunder
authors.initials: S
authors.lastname: Mudaliar
authors.forename: Robert E
authors.initials: RE
authors.lastname: Ratner
authors.forename: Ken
authors.initials: K
authors.lastname: Williams
authors.forename: Frankie B
authors.initials: FB
authors.lastname: Stentz
authors.forename: Nicolas
authors.initials: N
authors.lastname: Musi
authors.forename: Peter D
authors.initials: PD
authors.lastname: Reaven
mesh_terms: D000293:Adolescent; D000328:Adult; D001786:Blood Glucose / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000517:prevention & control*; D004311:Double-Blind Method; D004487:Edema / Q000139:chemically induced; D005500:Follow-Up Studies; D018149:Glucose Intolerance / Q000150:complications / Q000188:drug therapy*; D005951:Glucose Tolerance Test; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D007333:Insulin Resistance; D053208:Kaplan-Meier Estimate; D015993:Life Tables; D008875:Middle Aged; D000077205:Pioglitazone; D016016:Proportional Hazards Models; D045162:Thiazolidinediones / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D015430:Weight Gain / Q000187:drug effects; D055815:Young Adult
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D045162:Thiazolidinediones; D000077205:Pioglitazone