Efficacy Study of Pioglitazone Compared to Glimepiride on Coronary Atherosclerotic Disease Progression in Subjects With Type 2 Diabetes Mellitus
Condition: Diabetes Mellitus
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2
Study type: Interventional
Phase: Phase 3

Summary: 
      The purpose of this study was to determine the efficacy of pioglitazone, once daily (QD),
      compared to glimepiride on atherosclerotic disease measured by intravascular ultrasound.
    

Detailed description: 
      Diabetes is a chronic disease with multiple metabolic defects that result in hyperglycemia
      arising from inadequate insulin activity. Type 2 diabetes is usually the result of a
      progression from reduced sensitivity of hepatic and peripheral tissue cells to circulating
      insulin (ie, insulin resistance) to a progressive inability of the body to produce adequate
      insulin to overcome insulin resistance (ie, insulin deficiency due to beta-cell
      insufficiency) 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. The goal of treating type 2 diabetes is to control
      blood glucose and thereby prevent long-term complications. Adequate glycemic control is
      paramount in attempting to avert chronic complications, including blindness; renal
      dysfunction resulting in dialysis or renal transplantation; neuropathy; non-traumatic
      amputations; and macrovascular complications, including myocardial ischemia and myocardial
      infarction, stroke, and peripheral arterial disease. Intensive glucose management in the
      early stages of diabetes may help forestall such complications.

      Therapeutic agents have been developed to address each of the major functional metabolic
      defects associated with type 2 diabetes: decreased beta-cell function, elevated hepatic
      glucose output, and insulin resistance. Thiazolidinediones increase glucose utilization,
      decrease gluconeogenesis, and increase glucose disposal by binding to nuclear receptors known
      as peroxisome proliferator-activated receptors. Thiazolidinediones reduce insulin resistance
      by enhancing insulin sensitivity in muscle cells, adipose tissue, and hepatic cells
      (inhibiting hepatic gluconeogenesis), with no direct impact on insulin secretion. Thus,
      thiazolidinediones improve glycemic control and result in reduced levels of circulating
      insulin without predisposing patients to hypoglycemia. Peroxisome proliferator-activated
      receptors are found in tissues important for insulin action, such as adipose tissue, skeletal
      muscle, and the liver. The greatest concentration of peroxisome proliferator-activated
      receptors-gamma receptors is in adipose tissue.

      This study was designed to compare the effects of pioglitazone compared to glimepiride on
      progression of atherosclerotic disease, as measured by intravascular ultrasound.
    

Intervention name(s): Pioglitazone; Glimepiride
Intervention type(s): Drug; Drug
Intervention description(s): Up to 45 mg pioglitazone (optimized for glucose control), tablets, orally, once daily for up to 72 weeks.; Up to 4 mg of glimepiride (optimized for glucose control), tablets, orally, once daily for up to 72 weeks.
Other intervention name(s): ACTOS®; AD4833
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; Atherosclerosis