Efficacy Study of Pioglitazone and Glimepiride on the Rate of Progression of Atherosclerotic Disease.

Inclusion Criteria * Females of childbearing potential who are sexually active must agree to use adequate contraception, and can neither be pregnant nor lactating from Screening throughout the duration of the study. Women of childbearing potential must have a negative serum pregnancy test within 48 hours prior to the time of randomization. * Diagnosis of type 2 diabetes mellitus. * Has received appropriate counseling on lifestyle modification for type 2 diabetes, including diet and exercise. * Naïve to or not currently taking antidiabetic therapy, or is currently treated with monotherapy or combination antidiabetic therapy. * Glycosylated hemoglobin greater than or equal to 6.0% and less than 9% at screening if taking antidiabetic medication or glycosylated hemoglobin greater than or equal to 6.5% and less than 10% at screening if naïve to or not taking antidiabetic medication. Exclusion Criteria * Type 1 diabetes mellitus. * Taking more than 2 antidiabetic therapies at screening. For combination medications, each component is counted as 1 therapy. * Symptomatic coronary artery disease, cerebrovascular disease, or peripheral vascular disease at the time of screening. * Taking or have taken pioglitazone or other thiazolidinediones within 12 weeks of randomization or were discontinued from thiazolidinedione therapy due to lack of efficacy or clinical or laboratory signs of intolerance. * Was discontinued from glimepiride or other sulfonylureas due to lack of efficacy or clinical or laboratory signs of intolerance. * Participating in another investigational study or has participated in an investigational study within the past 30 days or is scheduled to participate in an investigational study during the time frame of this study. * Women who are pregnant, intend to become pregnant during the course of the study, or are lactating. * Men who have serum creatinine greater than or equal to 2.0 mg/dL (greater than or equal to 1.5 mg/dL if taking metformin) and women with serum creatinine greater than or equal to 1.8 mg/dL (greater than or equal to1.4 mg/dL if taking metformin). * Unexplained microscopic hematuria of greater than plus 1 confirmed by repeat testing. * History of drug abuse or a history of alcohol abuse (defined as regular or daily consumption of more than 4 alcoholic drinks per day) within the past 2 years. * Clinical cardiac failure as defined by New York Heart Association class III or IV, or known left ventricular dysfunction measured as left ventricular ejection fraction less than 40%, or by current use of diuretics or angiotensin converting enzyme inhibitors for the treatment of heart failure. Use of these agents for other therapeutic reasons is not an exclusion. * Alanine transaminase level of greater than 2.5 times the upper limit of normal, active liver disease or jaundice. * Weighs greater than 300 pounds or has a body mass index greater than 45 kg/m2 as calculated by weight (kg)/height (m)2 or weight (pounds)/height (inches)2 x 703. * Has taken excluded medications. * Known or suspected malignancy or recurrence of malignancy within the past 5 years, with the exception of basal cell carcinoma and Stage 1 squamous cell carcinoma of the skin. * Any disease where, in the opinion of the investigator, survival is expected to be less than 18 months. * Anticipated to undergo coronary bypass surgery or cardiac intervention during the course of the study. * Has, in the opinion of the investigator, clinically significant valvular heart disease likely to require surgical repair or replacement during the course of the study. * Has had uncontrolled hypertension (ie, sitting systolic blood pressure greater than160 mm Hg or sitting diastolic blood pressure greater than 100 mm Hg) at randomization. * Men who have hemoglobin less than10.5 g/dL and women who have hemoglobin less than10.0 g/dL. * Triglycerides greater than 500 mg/dL. * Unwilling or unable to comply with the protocol or scheduled appointments. * Unable to understand verbal and/or written English or any other language for which a certified translation of the informed consent is available. * Known or suspected hypersensitivity to blood, blood products, or albumin. * Subjects for whom it is not possible to obtain good quality images of the common carotid artery for technical reasons. * Potentially clinically significant stenosis of the carotid artery as determined according to current guidelines by the physician assessing carotid intima-media thickness results. In these cases, the carotid intima-media thickness results should be reviewed by the investigator in consultation with the carotid intima-media thickness physician prior to determining whether the subject should be randomized. * Has had bilateral endarterectomies, bilateral carotid stents, or radiation to the head or neck. * Has received radiation therapy in the past year, who has had more than one computed tomography scan in the past year, or who is unable to raise one's arms above one's head while in a prone position.