Pioglitazone Decreases Carotid Intima-Media Thickness Independently of Glycemic Control in Patients With Type 2 Diabetes Mellitus

Abstract

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 (HbA 1c ) 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.