Choice of monotherapy in newly diagnosed Type 2 diabetic patients: clinical perspective of ADOPT

A Diabetes Outcome Progression Trial (ADOPT) investigated the durability of the antihyperglycemic effects of rosiglitazone (RSG; maximum dose 4 mg twice daily), metformin (MET, maximum dose 1 g twice daily) and glyburide (or glibencamide [GB]; maximum dose 7.5 mg twice daily) in 4360 drug-naive patients with Type 2 diabetes mellitus. The therapeutic goal in the trial was a fasting plasma glucose level below 140 mg/dl (7.8 mmol/l) and the primary end point was the time from randomization to treatment failure, defined as an fasting plasma glucose above 180 mg/dl (10 mmol/l). The results showed a cumulative incidence of monotherapy failure at 5 years of 15% for RSG, 21% for MET and 34% for GB, equating to risk reductions in primary end point for RSG therapy of 32% relative to MET and 63% relative to GB (p < 0.001 for both comparisons). There were significant withdrawals from each of the study groups and when glycosylated hemoglobin was used as the measure of long-term glycemic control, the differences between groups were more modest. RSG also resulted in greater weight gain and, notably, a significantly increased fracture rate in the upper and lower limbs of women (9.3%) compared with MET (5.1%) and GB (3.5%). Overall, taking into account the modest glycemic benefit of RSG over MET, the cost difference between these treatments and safety concerns with RSG, MET remains the rational choice of initial treatment of Type 2 diabetes mellitus.