Anti-Inflammatory Effects of Pioglitazone

• Change from baseline in plasma glucose/insulin homeostatic parameters and circulating markers of atherosclerosis [ Time Frame: Baseline and 4 months and 5 years after treatment ] [ Designated as safety issue: Yes ]
• Change from baseline in visceral fat [ Time Frame: Baseline and 4 months and 5 years after treatment ] [ Designated as safety issue: Yes ]
• All cardiovascular events and all cause death for 5 years [ Time Frame: Baseline and 4 months and 5 years after treatment ] [ Designated as safety issue: Yes ]

There is increasing evidence that inflammation plays a role in progression and destabilization of atherosclerotic plaque. FDG-PET can visualize activated metabolic activity of inflammatory cells. It is possible that FDG-PET can detect atherosclerotic plaque inflammation and that FDG-PET can monitor the effect of pioglitazone on plaque inflammation.

Atherosclerotic patients with impaired glucose tolerance and type 2 diabetes will undergo the FDG-PET/CT imaging at baseline and again following 4 months after treatment. Patients who meet eligibility criteria will be titrated up to a maximum of 30 mg/day pioglitazone or 4 mg/day glimepiride. Physical examinations will be done at baseline, 4 months, and 12 months. During study, subjects will have body weight, and vital signs (HR, BP, etc) assessed as well as waist circumference. Laboratory assessments will be done at each baseline, 4 month.

• Impaired Glucose Tolerance
• Type 2 Diabetes Mellitus
• Atherosclerosis

• Drug: Pioglitazone
  Subjects who meet eligibility criteria will be titrated up to a maximum of 30 mg/day pioglitazone.
  Other Name: CAS number: 111025-46-8, ATC code: A10BG03
• Drug: Glimepiride
  Subjects who meet eligibility criteria will be titrated up to a maximum of 4 mg/day glimepiride.
  Other Name: CAS number: 93479-97-1, ATC code: A10BB12

• Experimental: 1
  up to 30 mg pioglitazone, tablet, orally, once daily
  Intervention: Drug: Pioglitazone
• Active Comparator: 2
  up to 4 mg/day glimepiride, tablet, orally, once daily
  Intervention: Drug: Glimepiride

Inclusion Criteria:

• Subjects between the ages of 35 and 85 years
• Subjects with impaired glucose tolerance and type 2 diabetes, who had atherosclerosis detected by carotid ultrasound and/or CT
• Subjects who had vascular FDG uptake by FDG-PET

Exclusion Criteria:

• Subjects with insulin treatment
• Subjects with uncontrolled diabetes, hypertension, symptomatic coronary artery disease, symptomatic cerebrovascular disease
• Subjects taking more than three antidiabetic medications
• Subjects taking anti-platelet, statins, antidiabetic agents, thiazolidinediones (TZDs) within 8 weeks prior to randomization
• Subjects with cardiac failure (New York Heart Association Class > III) or left ventricular dysfunction (LVEF < 40%)
• Subjects with systemic disorders such as active inflammatory, liver, renal, hematopoietic, and malignant disease