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

• Published in: Pediatric diabetes Vol. 9; no. 6; pp. 554 - 560
• Main Authors: Danne, Thomas, Datz, Nicolin, Endahl, Lars, Haahr, Hanne, Nestoris, Claudia, Westergaard, Lisbet, Fjording, Marianne Scheel, Kordonouri, Olga
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01-12-2008
• Subjects: Adolescent; Child; Cross-Over Studies; Diabetes Mellitus, Type 1 - drug therapy; Double-Blind Method; Female; Humans; Insulin - analogs & derivatives; Insulin - pharmacokinetics; Insulin Detemir; Insulin Glargine; Insulin, Long-Acting; Male; pediatric; type 1 diabetes; within-subject variability
• ISSN: 1399-543X; 1399-5448
• DOI: 10.1111/j.1399-5448.2008.00443.x

:  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 (Cmax), 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.