Insulin detemir is characterized by a more reproducible pharmacokinetic profile than insulin glargine in children and adolescents with type 1 diabetes: results from a randomized, double-blind, controlled trial*

Abstract

Original ArticleInsulin detemir is characterized by a more reproducible pharmacokinetic profile than insulin glargine in children and adolescents with type 1 diabetes: results from a randomized, double-blind, controlled trial* Danne T, Datz N, Endahl L, Haahr H, Nestoris C, Westergaard L, Fjording MS, Kordonouri O. Insulin detemir is characterized by a more reproducible pharmacokinetic profile than insulin glargine in children and adolescents with type 1 diabetes: results from a randomized, double-blind, controlled trial. Pediatric Diabetes 2008: 9: 554-560.Abstract: Insulin detemir (detemir) has previously been shown to be associated with lower within-subject variability compared with other basal insulin preparations in adults with type 1 diabetes mellitus (T1DM). This randomized, double-blind, crossover trial compared the withinsubject variability of detemir and insulin glargine (glargine) in pharmacokinetic properties in children and adolescents with T1DM. The trial enrolled 32 children and adolescents (19 girls and 13 boys; mean AE SD: age 13 AE 2.5 yr and T1DM duration 6.3 AE 3.0 yr) with a hemoglobin A1c (HbA1c) of 7.9 AE 1.0%. Participants were randomized to a specific treatment sequence in which a dose of 0.4 U/kg of detemir and glargine was injected subcutaneously 24 h apart at each of two dosing visits. Insulin concentrations were measured at frequent intervals for a period of 16-h post-dosing. Detemir showed statistically significantly less within-subject variability compared with glargine with a 3.1-fold and 2.9-fold lower coefficient of variation (CV, %) for the area under the concentration-time curve ] and the maximum concentration (C max ), respectively. Separate analyses demonstrated a 2.5-fold and 2.9-fold lower CV (%) with detemir in children (8-12 yr) and a 4-fold and 3.8-fold lower CV (%) with detemir in adolescents (13-17 yr). No safety concerns were raised during the trial. In conclusion, within-subject variability in pharmacokinetic properties was significantly lower for detemir than for glargine in children and adolescents with T1DM. This indicates a less variable absorption with detemir, which is expected to be associated with a more predictable therapeutic effect also in this population.

Once daily insulin detemir in cystic fibrosis with insulin deficiency

“…Once daily insulin detemir has not been studied. Insulin detemir has a stable absorption profile, with day-to-day variability less than that of insulin glargine and markedly less than that of insulin NPH 5 6. When given once daily with breakfast, detemir has the potential to avoid hypoglycaemia (particularly nocturnal).…”

Influence of the Type of Basal Insulin and Other Variables on Clinical Outcomes in Children with Newly Diagnosed Type 1 Diabetes

“…Glargine has a duration of action independent of dose and should theoretically last longer for young patients taking small doses (<0.4 units/kg/day) than detemir, which has a dose-dependent duration of action [3]. However, two studies found lower within-subject variability with detemir, one of these studies being performed in children [5, 6]. Conflicting data exists as to the HbA1c lowering effect of detemir compared to glargine, with studies finding no difference, a decrease, and an increase [7–9].…”

“…Another study examined the AUC of insulin concentration in children and adolescents with type 1 diabetes. It found significantly less within-subject variability with detemir in comparison to glargine; however the measurements only continued for 16 hours after the dose and perhaps did not reflect the variable duration of detemir [6]. …”

Abstract 14

“…for infants and toddlers who are reluctant to eat). Insulin detemir is approved for children above 2 years of age and has shown lowest within-subject variability,[30] reduced hypoglycemia rates, improved adherence, and greater treatment satisfaction. [2328]…”