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

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 (HbA(1c)), 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/m(2); HbA(1c), 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.