Pioglitazone decreases carotid intima-media thickness independently of glycemic control in patients with type 2 diabetes mellitus: results from a controlled randomized study

Circulation. 2005 May 17;111(19):2525-31. doi: 10.1161/01.CIR.0000165072.01672.21. Epub 2005 May 9.


Background: Patients with type 2 diabetes mellitus are at high risk of cardiovascular disease. Carotid intima-media thickness (IMT) is a strong predictor of myocardial infarction and stroke.

Methods and results: We compared the effects of pioglitazone-based therapy (45 mg/d) and glimepiride-based treatment (2.7+/-1.6 mg/d) for 12 and 24 weeks on metabolic control (HbA1c), insulin resistance (homeostasis model assessment), and carotid IMT (B-mode ultrasonography) in a randomized controlled study in 173 orally treated patients with type 2 diabetes (66 women, 107 men; mean+/-SD age, 62.6+/-7.9 years; body mass index, 31.8+/-4.6 kg/m2; HbA1c, 7.5+/-0.9%). Treatment was generally well tolerated in both groups. Despite similar improvements in metabolic control (HbA1c) after 24 weeks (-0.8+/-0.9% [pioglitazone] versus -0.6+/-0.8% [glimepiride]; P=NS), carotid IMT was reduced only in the pioglitazone group after 12 weeks (-0.033+/-0.052 versus -0.002+/-0.047 mm [glimepiride]; P<0.01 between groups) and 24 weeks (-0.054+/-0.059 versus -0.011+/-0.058 mm [glimepiride]; P<0.005 between groups). Insulin resistance was also improved only in the pioglitazone group (homeostasis model assessment, -2.2+/-3.4 versus -0.3+/-3.3; P<0.0001 between groups). Reduction of IMT correlated with improvement in insulin resistance (r=0.29, P<0.0005) and was independent of improvement in glycemic control (r=0.03, P=0.68).

Conclusions: We found a substantial regression of carotid IMT, independent of improved glycemic control, after 12 and 24 weeks of pioglitazone treatment. This finding may have important prognostic implications for patients with type 2 diabetes mellitus.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Cardiovascular Diseases / etiology
  • Cardiovascular Diseases / prevention & control
  • Carotid Arteries / pathology*
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Female
  • Humans
  • Hyperglycemia / drug therapy*
  • Hypoglycemic Agents / administration & dosage*
  • Hypoglycemic Agents / pharmacology
  • Insulin Resistance
  • Male
  • Middle Aged
  • Pioglitazone
  • Prognosis
  • Thiazolidinediones / administration & dosage*
  • Thiazolidinediones / pharmacology
  • Treatment Outcome
  • Tunica Intima / drug effects*
  • Tunica Media / drug effects*


  • Hypoglycemic Agents
  • Thiazolidinediones
  • Pioglitazone