A randomized, controlled trial of the effects of rosiglitazone on adipokines, and inflammatory and fibrinolytic markers in diabetic patients: study design and protocol.

BACKGROUND:Although rosiglitazone may offer vascular benefits beyond lowering glucose, recently, concern has been raised that this drug may paradoxically increase cardiovascular risk. OBJECTIVE:To assess the effects of rosiglitazone compared with standard oral hypoglycemic therapies on adipokines, and inflammatory and fibrinolytic markers in subjects with type 2 diabetes. METHODS:A 12-week, randomized, open-label, parallel-group study will be conducted on 100 type 2 diabetic subjects with suboptimal glycemic control (glycosylated hemoglobin 0.075 or greater) despite management with lifestyle alone (drug-naive) or with monotherapy (either metformin or sulfonylurea). Drug-naive patients will be randomly assigned to receive either rosiglitazone (4 mg/day to 8 mg/day) or metformin (500 mg/day to 2000 mg/day). Patients on pre-existing monotherapy will be randomly assigned to the addition of rosiglitazone (4 mg/day to 8 mg/day), or to either metformin (500 mg/day to 2000 mg/day) or glyburide (5 mg/day to 20 mg/day) (depending on background treatment). The primary end point of the study is the change in adiponectin level (from baseline to 12 weeks) in the rosiglitazone versus metformin or sulfonylurea arms. Secondary end points include changes in leptin, high-sensitivity C-reactive protein, interleukin-6, tumour necrosis factor-alpha, matrix metalloproteinase-9, vascular cell adhesion molecule-1, plasminogen activator inhibitor type 1, insulin sensitivity, glycosylated hemoglobin and lipid levels. Additionally, all patients will be required to be treated with an inhibitor of the renin-angiotensin system, namely an angiotensin receptor antagonist, as per national diabetes treatment guidelines, to a target systolic blood pressure of less than 130 mmHg and a diastolic blood pressure of less than 80 mmHg, or for the optimal suppression of microalbuminuria.