Abstract
In a randomized multicenter open-label parallel group trial, we compared efficacy and safety of insulin detemir (detemir), a novel long-acting soluble insulin analogue, versus neutral protamine hagedorn (NPH) insulin in subjects with type 2 diabetes treated with an oral hypoglycemic agent (OHA). Subjects were 371 insulin-naïve subjects with type 2 diabetes treated with an OHA and randomly assigned either to the detemir or NPH group. 180 subjects were exposed to detemir and 183 to NPH once daily for 36 weeks.
The mean difference (detemir-NPH) in the primary endpoint, baseline-adjusted HbA1c at end of trial was 0.07%, 95% confidence interval for the difference being (-0.07, 0.21), which satisfied the predefined criterion for claiming noninferiority that the upper limit of the confidence interval should be less then 0.4%. The noninferiority of detemir to NPH was established in glycemic control as assessed by HbA1c. No significant interaction on HbA1c was seen between treatment and OHA treatment. Fasting plasma glucose at end of trial decreased by an average of 40 mg/dl from baseline in both treatment groups. The mean daily insulin dose at end of trial was 0.17 unit/kg in the detemir group and 0.14 unit/kg in the NPH group, the dose ratio (detemir/NPH) being 1.189.
The incidences of both daily hypoglycemia and nocturnal hypoglycemia were lower in the detemir group than in the NPH group, but differences were not statistically significant. The relative risk (detemir/NPH) of having daily hypoglycemia was 0.71 and that of having nocturnal hypoglycemia was 0.60, respectively. The baseline-adjusted mean body weight at end of trial was significantly lower in the detemir group than in the NPH group (p=0.04). Other safety parameters, including the incidence of adverse events and laboratory parameters, were similar in the two treatment groups. Subjects treated with insulin detemir showed a significantly higher development of insulin detemir-specific and cross-reacting antibodies, compared to subjects treated with NPH, but no positive correlation was observed between antibody development and change in HbA1c from baseline, suggesting that glycemic control was not impaired because of increased antibodies and that no findings suggesting formation of neutralizing antibodies were seen.
Based on the results and the benefits of detemir, once-daily insulin detemir treatment add-on to OHA is considered useful in treatment of patients with type 2 diabetes mellitus.
