Efficacy Study of Pioglitazone and Glimepiride on the Rate of Progression of Atherosclerotic Disease.
Condition: Diabetes Mellitus
MeSH terms: Diabetes Mellitus
Study type: Interventional
Phase: Phase 3

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.
    

Intervention name(s): Pioglitazone; Glimepiride
Intervention type(s): Drug; Drug
Intervention description(s): Pioglitazone 15 mg titrated up to 45 mg, tablets, orally, once daily and glimepiride placebo-matching capsules, orally, once daily for up to 72 weeks.; Pioglitazone placebo-matching tablets, orally, once daily and glimepiride 1 mg titrated up to 4 mg, capsules, orally, once daily for up to 72 weeks.
Other intervention name(s): Actos; AD-4833; Amaryl
Intervention MeSH terms: Pioglitazone; Glimepiride
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Glucose Metabolism Disorder; Dysmetabolic Syndrome; Type II Diabetes; Diabetes Mellitus, Lipoatrophic; Dyslipidemia; Drug Therapy