Abstract
In a randomized multicenter open-label parallel group trial, we compared 48-week treatment efficacy and safety of insulin detemir (detemir), a novel long-acting soluble insulin analogue, versus neutral protamine hagedorn (NPH) insulin in subjects with insulin requiring diabetes mellitus in a basal-bolus regimen.
Subjects were 294 with type 1 diabetes (detemir group: 196, NPH group: 98) and 102 with type 2 diabetes (detemir group: 67, NPH group: 35).
In those with type 1 diabetes, the mean difference (detemir-NPH) in the primary endpoint, HbA1c at the end of the trial was 0.03%, with the 95% confidence interval for the difference being (-0.14, 0.21), which satisfied the predefined criterion for claiming noninferiority that the upper limit of confidence interval should be less than 0.4%. The noninferiority of insulin detemir to NPH was thus established in glycemic control as assessed by HbA1c in subjects with type 1 diabetes. Baseline-adjusted mean fasting plasma glucose (FPG) (before breakfast) at the end of the trial and intrasubject variability of FPG alike were significantly lower in the detemir group than in the NPH group. Subjects in the detemir group had a significantly lower risk of nocturnal hypoglycemia compared to those in the NPH group (p<0.05), the relative risk (detemir/NPH) being 0.69 [95% confidence interval of (0.47, 0.99)]. The baseline-adjusted mean body weight at the end of the trial was significantly lower in the detemir group than in the NPH group.
Other safety parameters, including the incidence of adverse events and laboratory parameters, were similar in the two groups. An evaluation of insulin antibodies indicated an increase in detemir-specific antibodies, but no positive correlation was observed between the change in cross-reacting antibodies and the change in HbA1c from baseline, suggesting that glycemic control was not impaired due to the antibody increase.
The sample size in the subgroup with type 2 diabetes was small and should be taken into account in interpreting results in type 2 diabetic subjects, which were generally similar to those in type 1 diabetes.
Based on these results and the benefits of detemir, insulin detemir is considered useful as a basal insulin with no safety concerns.
