title: Long-term effects of pioglitazone on carotid atherosclerosis in Japanese patients with type 2 diabetes without a recent history of macrovascular morbidity.
abstract: OBJECTIVE
  No previous studies have evaluated the long-term anti-atherosclerotic effects of pioglitazone in Asian patients with type 2 diabetes. Therefore, the present study investigated the protective effects of pioglitazone on the progression of carotid intima-media thickness (IMT), an established surrogate marker of cardiovascular events in Japanese type 2 diabetic patients without a recent history of cardiovascular morbidity.
  
  
  METHODS
  This 2.5-4-year, randomized, open-label, blinded endpoint study was conducted in 6 centers across Japan. Patients received pioglitazone with or without other oral glucose-lowering drugs (excluding another thiazolidinedione) (n=89) or oral glucose-lowering drugs, excluding thiazolidinediones (n=97). Treatment was adjusted to achieve HbA(1c) <6.5%. The primary endpoints of the study were the absolute changes from the baseline to final visit in max- and mean-IMT in the average of bilateral common carotid arteries.
  
  
  RESULTS
  Pioglitazone induced carotid IMT regression compared to baseline measurements (from 1.060 ± 0.2368 to 0.992 ± 0.1921 mm; p=0.0042 in max-IMT and from 0.839 ± 0.1873 to 0.780 ± 0.1571 mm; p=0.0019 in mean-IMT). Although the between-group difference did not reach statistical significance, the regression of carotid IMT values was greater in the pioglitazone-treatment group than in the non-pioglitazone group, (max-IMT: -0.069 ± 0.2199 mm vs -0.031 ± 0.2327 mm, respectively; p=NS, mean-IMT: -0.058 ± 0.1718 mm vs -0.043 ± 0.1644 mm, respectively; p=NS).
  
  
  CONCLUSIONS
  Pioglitazone induced and maintained the long-term regression of carotid IMT in Japanese type 2 diabetic patients. This suggests that pioglitazone may inhibit the progression of atherosclerosis in this patient group. Further studies are required to verify these findings.
authors.affiliation: Department of Internal Medicine and Therapeutics, Osaka University Graduate School of Medicine, Osaka, Japan. yamasaki@medone.med.osaka-u.ac.jp
authors.forename: Yoshimitsu
authors.initials: Y
authors.lastname: Yamasaki
authors.forename: Naoto
authors.initials: N
authors.lastname: Katakami
authors.forename: Shigetaka
authors.initials: S
authors.lastname: Furukado
authors.forename: Kazuo
authors.initials: K
authors.lastname: Kitagawa
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Nagatsuka
authors.forename: Atsunori
authors.initials: A
authors.lastname: Kashiwagi
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Daida
authors.forename: Ryuzo
authors.initials: R
authors.lastname: Kawamori
authors.forename: Kohei
authors.initials: K
authors.lastname: Kaku
mesh_terms: D000328:Adult; D000368:Aged; D044466:Asian People; D002339:Carotid Arteries / Q000187:drug effects; D002340:Carotid Artery Diseases / Q000188:drug therapy* / Q000473:pathology; D016022:Case-Control Studies; D015897:Comorbidity; D048909:Diabetes Complications / Q000188:drug therapy*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D000077205:Pioglitazone; D011379:Prognosis; D011446:Prospective Studies; D045162:Thiazolidinediones / Q000627:therapeutic use*; D013997:Time Factors; D017539:Tunica Intima / Q000187:drug effects; D017540:Tunica Media / Q000187:drug effects
chemical_list: D007004:Hypoglycemic Agents; D045162:Thiazolidinediones; D000077205:Pioglitazone