A 52-Week, Multinational, Open-Label, Parallel-Group, Noninferiority, Treat-to-Target Trial Comparing Insulin Detemir with Insulin Glargine in a Basal-Bolus Regimen with Mealtime Insulin Aspart in Patients with Type 2 Diabetes

Objective: This trial compared the efficacy and safety profiles of the insulin analogues detemir and glargine as the basal Insulin component of a basal-bolus regimen in patients with type 2 diabetes mellitus (T2DM) who were being treated with oral antidiabetic drugs (OADs) or insulin with or without OADs. Methods: This was a multinational, 52-week, open-label, parallel-group, noninferiority, treat-to-target trial. Patients with a diagnosis of T2DM for >= 12 months who had been receiving an OAD or insulin, with or without OADs, for >4 months were randomized in a 2:1 ratio to receive detemir or glargine. According to the approved labeling, detemir could be administered once or twice daily, and glargine was administered once daily. Insulin aspart was given at mealtimes. Insulin secretagogues and alpha-glucosidase inhibitors were discontinued at study entry, and existing OADs were Continued. Doses of detemir and glargine were titrated to achieve a prebreak-fast (and predinner for detemir administered twice daily) plasma glucose target of <= 6.0 mmol/L. Patients monitored their plasma glucose levels before breakfast and dinner on the 3 days before each of 13 scheduled visits, recorded their insulin doses on I of these 3 days, and recorded their 10-point self-monitored plasma glucose (SMPG) at baseline and after 24 and 52 weeks. The primary efficacy end point was glycosylated hemoglobin (HbA(1c)) at 52 weeks; secondary efficacy end points included changes in fasting plasma glucose (FPG), postprandial plasma glucose, insulin doses, and weight change at 52 weeks. Safety end points included the frequency of hypoglycemia and adverse events (AEs). Results: The intention-to-treat population Included 319 patients (58.0% male, 42.0% female; 78.4% white; mean age, 58 years; mean weight, 92.8 kg; mean duration of diabetes, 13.6 years). At study entry, 46.1% of patients were receiving insulin and >= 1 OAD, 35.4% were receiving insulin only, and 18.5% were receiving >= 1 OAD only. At 52 weeks, there was no significant difference between detemir and glargine in terms of mean HbA(1c) (7.19% and 7.03%, respectively; mean difference, 0.17% [95% CI, -0.07 to 0.40]) or the mean decrease in HbA(1c) from baseline (-1.52% and -1.68%). The reduction in HbA(1c) was not significantly affected by whether detemir was administered once or twice daily There were no significant differences between groups in terms of mean FPG (7.05 and 6.68 mmol/L) or the mean change in FPG from baseline (-2.56 and -2.92 mmol/L; mean difference, 0.36; 95% CI, -0.26 to 0.99). The overall shape of the 10-point SMPG profiles was not significantly different between groups. Mean weight gain at 52 weeks was significantly lower with detemir than with glargine (2.8 vs 3.8 kg; mean difference, -.1.04; 95% CI, -2.08 to -0.0 1; P < 0.05). Doses of basal and prandial insulins at the end of the Study were not significantly different between groups. Major hypoglycemic episodes were reported by 4.7% and 5.7% of patients in the respective treatment groups. There was no significant difference in the risk of hypoglycemia between groups. The proportion of patients with AEs and the number of AEs per patient were comparable between groups (185/214 patients [86.4%] reporting 743 AEs and 88/105 patients [83.8%] reporting 377 AEs). Conclusions: When used as indicated as part of a basal-bolus regimen in patients with T2DM who had previously received other insulin and/or OAD regimens, detemir was noninferior to glargine in its effects on overall glycemic control. Both basal insulins were associated with clinically relevant reductions in hyperglycemia. Both were well tolerated, with no significant difference in the frequency of hypoglycemia or AEs. (Clin Ther. 2008;30:1976-1.987) (C) 2008 Excerpta Medica Inc.