Published online before print May 9, 2005, doi: 10.1161/01.CIR.0000165072.01672.21
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(Circulation. 2005;111:2525-2531.)
© 2005 American Heart Association, Inc.
Vascular Medicine |
Pioglitazone Decreases Carotid Intima-Media Thickness Independently of Glycemic Control in Patients With Type 2 Diabetes Mellitus
Results From a Controlled Randomized Study
From the Institute of Clinical Research and Development, Mainz (M.R.L., T.F., C.H., A.P.); Division of Endocrinology and Diabetology, Philipps University Medical School, Marburg (P.K.); Takeda Pharma, Aachen (G.L.); Institut für Stoffwechselforschung, Frankfurt (T.K., S.D.F.); ClinResearch GmbH, Cologne (C.S.); and University of Applied Sciences, Rheinbach (A.P.), Germany.
Correspondence to Professor Andreas Pfützner, MD, PhD, Institute of Clinical Research and Development GmbH, Parcusstr 8, 55116 Mainz, Germany. E-mail AndreasP{at}ikfe.de
Received July 29, 2004; revision received January 27, 2005; accepted January 28, 2005.
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.
Key Words: atherosclerosis • carotid arteries • diabetes mellitus • insulin resistance
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