The purpose of this study is to evaluate the cardiovascular effects of pioglitazone, once daily (QD), versus glyburide when administered to patients with type 2 diabetes mellitus and mild cardiac disease.
Diabetes is a chronic disease involving multiple metabolic defects that include inadequate insulin activity and resultant hyperglycemia. Individuals' differing genetic predisposition, level of physical activity, and age all contribute to variations in the onset and severity of type 2 diabetes. However, progression of this disease typically follows a characteristic pattern that begins as a reduced sensitivity of hepatic and peripheral-tissues to circulating insulin (ie, insulin resistance). The body's decreasing ability to produce adequate insulin to overcome insulin resistance (ie, insulin deficiency due to beta-cell insufficiency) results in impaired glucose tolerance and ultimately overt diabetes. In the United States, an estimated 17 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 and resultant dialysis or renal transplantation, neuropathy, and nontraumatic amputations. Intensive glucose management in the early stages of diabetes may help forestall complications. Pioglitazone is a thiazolidinedione developed by Takeda Chemical Industries, Ltd. Glyburide, is an oral antidiabetic agent of the sulfonylurea class. The primary purpose of this study is to evaluate the cardiovascular effects of pioglitazone versus glyburide when administered to patients with type 2 diabetes mellitus and mild cardiac disease Study participation is anticipated to be approximately 1 year and 2 weeks.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
300
Pioglitazone 15 mg to 45 mg, tablets, orally, once daily and glyburide placebo-matching capsules, orally, once daily for up to 52 weeks.
Glyburide 2.5 mg to 15 mg, capsules, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 52 weeks.
Pioglitazone 15 mg or 30 mg, tablets, orally, once daily and glyburide placebo-matching capsules, orally once daily for up to 52 weeks.
Change in the walking distance during a standardized 6-minute walk test.
Time frame: Weeks 2, 16, 24, 40, and 52 or Final Visit
Morbidity and Mortality Due to Cardiovascular Events.
Time frame: At occurrence or Weeks 2, 4, 6, 8, 12, 16, 24, 32, 36, 40, 48, and 52 or Final Visit
Change in Cardiovascular Treatment Program.
Time frame: At occurrence or Weeks 2, 4, 6, 8, 12, 16, 24, 32, 36, 40, 48, and 52 or Final Visit
Change from Baseline in 12-lead Electrocardiogram Parameter (Ventricular Heart Rate)
Time frame: Weeks 24 and 52 or Final Visit
Change from Baseline in Electrocardiogram Parameter (Left Ventricular Mass)
Time frame: Week 52 or Final Visit
Change from Baseline in Electrocardiogram Parameter (Left Ventricular Ejection Fraction)
Time frame: Week 52 or Final Visit
Change from Baseline in Electrocardiogram Parameter (Cardiac Index)
Time frame: Week 52 or Final Visit
Change from Baseline in Electrocardiogram Parameter (Fractional Shortening)
Time frame: Week 52 or Final Visit
Change in Blood Pressure
Time frame: Weeks 2, 4, 6, 8, 12, 16, 24, 32, 40, 48, and 52 or Final Visit
Change in Heart Rate
Time frame: Weeks 24 and 52 or Final Visit
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Glyburide 5 mg or 10 mg, capsules, orally, once daily and pioglitazone placebo-matching tablets, orally once daily for up to 52 weeks.
Change in Body Weight
Time frame: Weeks 2, 4, 6, 8, 12, 16, 24, 32, 40, 48, and 52 or Final Visit