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.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
547
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.
Nominal Change From Baseline in Percent Atheroma Volume
The nominal change from baseline in percent atheroma volume for all slices of anatomically comparable segments of the target coronary artery. Assessment completed at the Week 72 visit or Final Visit if treatment was prematurely discontinued.
Time frame: Baseline and Final Visit (up to 72 weeks)
Nominal Change From Baseline in Normalized Total Atheroma Volume
The nominal change in normalized total atheroma volume as measured by the average of plaque areas for all slices of anatomically comparable segments of the target coronary artery multiplied by the mean number of matched slices in the population. Assessment completed at the Week 72 visit or Final Visit if treatment was prematurely discontinued.
Time frame: Baseline and Final Visit (up to 72 weeks)
Number of Subjects Experiencing Any of the Composite Endpoint A Cardiovascular Events
Due to low event rates, number of subjects experiencing any of the composite endpoint A cardiovascular events is being reported instead of time to first occurrence. Endpoint A conditions listed in Limitations and Caveats section.
Time frame: Up to 72 weeks
Number of Subjects Experiencing Any of the Composite Endpoint B Cardiovascular Events
Due to low event rates, number of subjects experiencing any of the composite endpoint B cardiovascular events is being reported instead of time to first occurrence. Endpoint B conditions listed in Limitations and Caveats section.
Time frame: Up to 72 weeks
Number of Subjects Experiencing Any of the Composite Endpoint C Cardiovascular Events
Due to low event rates, number of subjects experiencing any of the composite endpoint C cardiovascular events is being reported instead of time to first occurrence. Endpoint C conditions listed in Limitations and Caveats section.
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...and 69 more locations
Time frame: Up to 72 weeks