Background: Many patients with poorly controlled type 2 diabetes mellitus (DM) receive, as initial insulin treatment, the addition of a basal formulation to an existing regimen of oral antidiabetic drug (OAD) therapy. Used this way, the insulin analogue detemir has been associated with improved glycemic control of a magnitude similar to neutral protamine Hagedorn (NPH), with lower rates of hypoglycemia and weight gain. Initial studies investigated detemir administered BID, but pharmacologic data suggest that detemir might be effective with QD administration.
Objectives: The aims of this study were to compare the effectiveness and tolerability of detemir versus NPH administered QD together with > or =1 OAD in poorly controlled type 2 DM, and to compare different administration times of detemir.
Methods: This 20-week, multicenter, randomized, open-label, 3-arm, parallel-group trial was conducted at 91 centers across Europe and the United States. Men and women were eligible for participation if they were aged > or =18 years, had a body mass index (BMI) < or =40 kg/m(2), had a diagnosis of type 2 DM of at least 12 months' duration, and were insulin naive. Eligible patients also had a glycosylated hemoglobin (HbA(1c)) concentration value not outside the range of 7.5% to 11.0% following at least 3 months' treatment with > or =10 AD. Patients were randomly assigned to receive an evening SC injection of detemir, a prebreakfast injection of detemir, or an evening injection of NPH insulin (1:1:1), administered at initial doses of 10 IU (U).
Results: A total of 504 patients were enrolled 5 men, 219 women; mean [SD] age, 59 [11] years; mean [SD] BMI, 30 [5] kg/m2; insulin detemir before breakfast, 168; insulin detemir evening, 170; NPH insulin evening, 166). The intent-to-treat population comprised 498 patients. Morning and evening detemir were associated with reductions in HbA(1c) similar to those with evening NPH (raw mean decreases, -1.58%, -1.48%, and -1.74%, respectively). Nine-point profile and fasting and predinner plasma glucose data found morning detemir to be associated with a different diurnal glycemic profile compared with the evening regimens. Compared with evening NPH, 24-hour and nocturnal hypoglycemia were reduced by 53% (P = 0.019) and 65% (P = 0.031), respectively, with evening detemir. Incidences of hypoglycemia did not differ significantly between groups that received morning and evening detemir, but nocturnal hypoglycemia was reduced further, by 87%, with morning detemir compared with evening NPH (P < 0.001). Weight gain was 1.2, 0.7, and 1.6 kg with morning detemir, evening detemir, and NPH, respectively (P = 0.005 for evening detemir vs NPH). No between-treatment differences were seen in other tolerability end points.
Conclusions: The results of this study in patients whose type 2 DM was poorly controlled with > or =1 OAD suggest that insulin detemir QD in the morning or evening can be used to improve glycemic control. Compared with NPH, insulin detemir may offer some tolerability advantages in this role.