rosiglitazone versus a sulfonylurea on progression of atherosclerosis in patients with heart disease and type 2 diabetes

Conditions: Atherosclerosis

Summary: the purpose of this study is to test the safety and effectiveness of rosiglitazone against a sulfonylurea in reducing or slowing the development of atherosclerosis in the blood vessels of the heart.


Eligibility criteria:
inclusion criteria: * male or female between 30 to 80 years of age, inclusive. * established diagnosis of t2dm (based on diagnostic criteria of the american diabetes association (ada), who guidelines or local national guidelines). * subjects who are undergoing coronary angiography for evaluation of suspected or previously diagnosed coronary artery disease or who are undergoing pci. * subjects' prior anti-hyperglycemic diabetic therapy: diet and exercise only (drug naïve), with hba1c \>7.0 and £ 10.0%. hba1c \> 6.5 and \<= 8.5%. * left ventricular ejection fraction (ef) ³ 40% as assessed by contrast ventriculography (or previously documented in medical notes within one month prior to index procedure by other methods e.g. echocardiography or nuclear study) * female subjects must be postmenopausal (i.e., \>6 months without menstrual period), surgically sterile, or using effective contraceptive measures (oral contraceptives, norplant, depo-provera, an intra-uterine device (iud), a diaphragm with spermicide or a condom with spermicide). women of childbearing potential must use effective contraceptive measures for at least 1 month prior to visit 1a, and should continue to use the same contraceptive method during the study and for 30 days after discontinuing study medication. * willingness and ability to give informed consent prior to entering the study and available to complete the study. exclusion criteria: * type 1 diabetes and/or history of diabetic ketoacidosis. * exposure to a tzd or other ppar-g agonist within the 6 months prior to screening visit. * subjects treated with triple oad therapy or high dose dual combination oad therapy \[1\]. * subjects who have required chronic insulin use in the last 6 months (except during pregnancy or acute episodes such as hospitalization, trauma or infection). * st segment elevation myocardial infarction in the last 30 days. * subjects who have a history or are scheduled to receive coronary artery bypass graft surgery (cabg), valve repair or replacement, aneurysmectomy or planned major non-cardiac surgery during the study period. * subjects who have severe cardiac valvular disease * stroke or resuscitated in the past 6 months * history of congestive heart failure (nyha class i - iv) * history of significant hypersensitivity or reaction (e.g., difficulty swallowing, difficulty breathing, tachycardia or skin reaction) to any tzd, su, biguanide or insulin * prior history of severe edema or edema requiring medical treatment. * chronic disease requiring chronic or intermittent treatment with oral, intravenous, or injected corticosteroids (use of topical, inhaled, or nasal corticosteroids is permissible). * recent history or suspicion of current drug abuse or alcohol abuse within the last 6 months. * untreated hypo- or hyperthyroidism * a diagnosis of cancer (other than superficial squamous, basal cell skin cancer, or adequately treated cervical carcinoma in situ) in the past 3 years or current treatment for the active cancer. * any clinically significant abnormality identified at the screening visit, physical examination, laboratory tests, or electrocardiogram which, in the judgement of the investigator, would preclude safe completion of the study. * blood pressure: sbp \>170 or dbp \> 100 mmhg * significant anemia (hemoglobin \< 11 g/dl for males and \< 10 g/dl for females). * significant renal disease manifested by serum creatinine (\> 1.5mg/dl for males or \> 1.4mg/dl for females), or where the use of metformin is contra-indicated. * hepatic disease or biliary tract obstruction, or significant hepatic enzyme elevation (alt or ast \> 2.5 times upper limit of normal (uln) or bilirubin \>2x uln). * history of myopathy or history of elevated creatine kinase (ck) \> 3 times upper normal limit. * use of an investigational drug within 30 days or 5 half-lives (whichever is the longer). * women who are lactating, pregnant or planning to become pregnant during the course of the study. * unwillingness or inability to comply with the procedures described in this protocol.

Keywords: atheroma ivus intravascular ultrasound atherosclerosis