Efficacy Study of Pioglitazone and Glimepiride on the Rate of Progression of Atherosclerotic Disease.
- Registration Number
- NCT00225264
- Lead Sponsor
- Takeda
- Brief Summary
The primary purpose of this study is to compare the effects of pioglitazone, once daily (QD), versus glimepiride on the amount of thickening of the carotid artery.
- Detailed Description
Diabetes is a chronic disease with multiple metabolic defects that result in hyperglycemia arising from inadequate insulin activity. Type 2 diabetes usually is the result of a progression from reduced sensitivity of hepatic and peripheral tissue cells to circulating insulin to a progressive inability of the body to produce adequate insulin to overcome insulin resistance, resulting in impaired glucose tolerance and ultimately overt diabetes. In the United States, an estimated 21 million people have diabetes, with type 2 diabetes occurring in approximately 90% to 95% of cases.
Type 2 diabetes also represents an important risk group for the development of accelerated atherosclerosis. Atherosclerosis can be measured with different procedures. One of the noninvasive, commonly used procedures is carotid B-mode ultrasound measurement of carotid intima-media thickness, which has been shown to be a useful measurement for clinical cardiovascular events in multiple studies.
Coronary artery calcification is a marker of coronary artery disease, and electron beam tomography is a sensitive tool for evaluation of coronary artery calcium. Electron beam tomography measurements produce a coronary artery calcium score that represents plaque burden. Subjects with diabetes mellitus have accelerated coronary artery disease. Even after treatment of elevated lipid levels, rates for coronary events still exceed those seen in non-diabetic subjects treated with the same lipid-lowering agents. Diabetic subjects also continue to have increased mortality rates compared with non-diabetic subjects after a myocardial infarction. Therefore, detection of sub-clinical atherosclerosis and prevention of myocardial infarction in subjects with diabetes remains an important priority.
Pioglitazone is a thiazolidinedione developed by Takeda Chemical Industries, Ltd, and depends on the presence of insulin for its mechanism of action. Data suggests that thiazolidinediones may inhibit the development of atherosclerosis in non-diabetic, atherosclerosis mouse models. These findings suggest that this class of drugs may have an effect on vessel walls to suppress development of atherosclerotic lesions.
This study will investigate the effects of pioglitazone and glimepiride on the rate of progression of atherosclerotic disease as measured by carotid intima-media thickness and by electron beam tomography of the coronary arteries in subjects with type 2 diabetes.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 458
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Pioglitazone QD Pioglitazone - Glimepiride QD Glimepiride -
- Primary Outcome Measures
Name Time Method Absolute change from Baseline in carotid intima-media thickness. Weeks 24, 48 and Final Visit.
- Secondary Outcome Measures
Name Time Method Change from Baseline in coronary artery calcium-volume score. At Final Visit Change from Baseline in abdominal adipose tissue content and distribution. At Final Visit Change from Baseline in carotid intima-media thickness. Weeks 24, 48 and Final Visit. Incidence of cardiovascular events as a composite of cardiovascular mortality, nonfatal MI, nonfatal stroke, coronary revascularization, carotid endarterectomy/stenting, hospitalization for unstable angina and hospitalization for CHF At each occurrence Incidence of cardiovascular events as a composite of cardiovascular mortality, nonfatal myocardial infarction and nonfatal stroke At each occurrence