title: 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: 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 within-subject 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 +/- SD: age 13 +/- 2.5 yr and T1DM duration 6.3 +/- 3.0 yr) with a hemoglobin A1c (HbA1c) of 7.9 +/- 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 [AUC((0-16) (h))] 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.
authors.affiliation: Center for Pediatric Endocrinology and Diabetes, Kinderkrankenhaus auf der Bult, Hannover Medical School, Hannover, Germany. danne@hka.de
authors.forename: Thomas
authors.initials: T
authors.lastname: Danne
authors.forename: Nicolin
authors.initials: N
authors.lastname: Datz
authors.forename: Lars
authors.initials: L
authors.lastname: Endahl
authors.forename: Hanne
authors.initials: H
authors.lastname: Haahr
authors.forename: Claudia
authors.initials: C
authors.lastname: Nestoris
authors.forename: Lisbet
authors.initials: L
authors.lastname: Westergaard
authors.forename: Marianne Scheel
authors.initials: MS
authors.lastname: Fjording
authors.forename: Olga
authors.initials: O
authors.lastname: Kordonouri