This study was designed to compare the safety and efficacy of pioglitazone HCl and glyburide
in the long-term (52 weeks) treatment of patients with type 2 diabetes mellitus and mild
cardiac disease (NYHA I).
Inclusion Criteria:
- Men or women greater or equal to 18 years and less than 80 years of age, diagnosed
with type 2 diabetes mellitus.
- Patients who were naïve to oral antidiabetic pharmacologic therapy, who were currently
taking sulfonylurea monotherapy, who were currently taking sulfonylurea/metformin
combination therapy, or who were currently taking metformin monotherapy. Patients who
were currently taking oral antidiabetic pharmacologic therapy must have been on a
stable dose for at least 30 days prior to Visit 1.
- Patients with mild cardiac disease (NYHA I).
- Patients who had participated in dietary counseling.
- HbA1c equal to or higher than 7. 5 percent and lower than 12 percent at Screening if
naïve to oral antidiabetic pharmacologic therapy or taking metformin monotherapy, or
equal to or higher than 6. 5 percent and lower than 12 percent if currently taking
sulfonylurea monotherapy or taking sulfonylurea/metformin combination therapy.
- Patients on stable therapy for cardiovascular dysfunction, defined as no change in
therapy for at least 4 weeks prior to Randomization.
Exclusion Criteria:
- Patients who within the past 30 days were treated with rosiglitazone, pioglitazone, or
troglitazone or those previously treated with rosiglitazone, pioglitazone, or
troglitazone but discontinued from therapy because of lack of efficacy or clinical or
laboratory signs of intolerance.
- Patients intolerant of or did not respond to prior sulfonylurea treatment.
- Patients who were currently taking insulin or had been on continuous insulin therapy
for control of their diabetes within 1 month of Screening.
- Patients with type 1 (insulin-dependent) diabetes mellitus or a history of
ketoacidosis.
- Pregnant or lactating women.
- Patients with cardiac disease and NYHA functional Class II, III, or IV at Screening,
or previous history of Class III or IV.
- Patients who had any of the following within 3 months prior to Visit 1: myocardial
infarction, coronary angioplasty or bypass graft, unstable angina pectoris, transient
ischemic attacks, or documented cerebrovascular accident that, in the investigator's
opinion, would warrant exclusion from the study.
- Abdominal, thoracic, or vascular surgery during the 3 months prior to Visit 1 that, in
the investigator's opinion, warranted exclusion from the study.
- BMI greater than 48 kg/m2 as calculated by [weight (kg)/height (m)2].
- Patients with anemia having hemoglobin below 10. 5 g/dL for men and 10. 0 g/dL for
women.
- Patients with a triglyceride level above 500 mg/dL.
- Patients with clinical evidence of active liver disease or alanine transaminase (ALT)
levels more than 2. 5 times the upper limit of normal.
- Serum creatinine above 2. 0 mg/dL for men and 1. 8 mg/dL for women or urinalysis protein
(albumin) excretion levels above 2+ on Combistix or equivalent and on repeat 24-hour
results with more than 3 g macroproteinuria (if elevated, may have been rescreened in
1 month).
- Patients with a systolic BP above 160 mm Hg or diastolic BP above 90 mm Hg at
Screening.
- Patients with symptomatic orthostatic hypotension or systolic BP below 90 mm Hg.
- Patients with severe, advanced peripheral vascular disease (limb-threatening ischemia)
or claudication resulting in the inability to walk more than 1 block or to climb 10
stairs without interruption.
- Patients with lower extremity amputation that would prevent the patient from
performing the exercise test.
