A diabetes outcome progression trial (ADOPT): an international multicenter study of the comparative efficacy of rosiglitazone, glyburide, and metformin in recently diagnosed type 2 diabetes.

OBJECTIVE: Therapies with metformin, sulfonylureas, or insulin improve glycemic control in the short term but do not prevent progressive islet beta-cell failure or long-term deterioration in glycemia. Our goal was to evaluate, in patients recently diagnosed with type 2 diabetes (<3 years), the long-term efficacy of monotherapy with rosiglitazone on glycemic control and on the progression of pathophysiological abnormalities associated with type 2 diabetes as compared with metformin or glyburide monotherapy. RESEARCH DESIGN AND METHODS: A Diabetes Outcome Progression Trial (ADOPT) is a randomized, double-blind, parallel-group study consisting of a screening visit, a 4-week placebo run-in, a 4-year treatment period, and an observational follow-up of approximately 3,600 drug-naïve patients with type 2 diabetes diagnosed within the previous 3 years. After run-in, patients will be randomized to rosiglitazone, glyburide, or metformin titrated to the maximum effective daily doses (8 mg rosiglitazone, 15 mg glyburide, or 2 g metformin). The primary outcome is time to monotherapy failure, defined as the time following titration to the maximal effective or tolerated dose when fasting plasma glucose exceeds 180 mg/dl (10 mmol/l). Secondary outcomes include measures of islet beta-cell function, insulin sensitivity, dyslipidemia, changes in urinary albumin excretion, plasminogen activator inhibitor-1 antigen, fibrinogen, and C-reactive protein. Safety and tolerability will also be evaluated. Patient-reported outcomes and resource utilization data will be collected and analyzed. CONCLUSIONS: ADOPT will provide data on the effect of mechanistically differing treatment options on metabolic control, beta-cell function, and markers of macrovascular disease risk in type 2 diabetes.

Efficacy and safety of rosiglitazone plus metformin in Mexicans with type 2 diabetes.

BACKGROUND: Type 2 diabetes is a growing problem in Mexico. The present study was undertaken to evaluate the efficacy and safety of rosiglitazone 2 mg or 4 mg twice daily (bd) in combination with metformin 2.5 g/day in Mexican patients whose type 2 diabetes was inadequately controlled with metformin alone. METHODS: This randomized, double-blind, placebo-controlled study was conducted at four centers in Mexico. A total of 116 patients were randomized to metformin 2.5 g/day plus placebo (n=39), metformin 2.5 g/day plus rosiglitazone 2 mg bd (n=37), or metformin 2.5 g/day plus rosiglitazone 4 mg bd (n=40) for 26 weeks. RESULTS: Mean hemoglobin A(1c) (HbA(1c)) levels decreased significantly from baseline to Week 26 in the rosiglitazone 2 mg bd (-0.7%; p=0.0052) and 4 mg bd (-1.2%; p=0.0008) groups, but increased in the placebo group (+0.3%; p=0.2651). Mean fasting plasma glucose and fructosamine levels also improved significantly with metformin plus rosiglitazone therapy in a dose-ordered manner compared with placebo (p