AIMS: This study investigated the
pharmacodynamic and
pharmacokinetic characteristics of the novel long-acting
insulin analogue insulin detemir (IDet) under single-dose and steady-state conditions in comparison with those of
NPH insulin at steady state. METHODS: Twenty-five subjects with
Type 1 diabetes [seven females, 18 males,
mean age (+/- sd) 39 +/- 12 years,
body mass index 24 +/- 3 kg/m(2)] participated in three 24-h
glucose clamps. IDet or NPH were given at 12-h intervals in fixed, individualized doses. The first clamp assessed the
metabolic effect of NPH at steady state, the second investigated the effect of two single injections of IDet. Subjects continued IDet treatment for 7-14 days, after which the third clamp was performed to investigate IDet at steady state. RESULTS: At steady state, the
metabolic effect of IDet was constant over 24 h while a clear peak in the
metabolic effect [expressed as
glucose infusion rates (GIR)] was observed with NPH after each injection. The fluctuation in the
metabolic effect (maximum GIR divided by the
average of the GIR values at the interval ends) was significantly lower in the second 12 h of the experiments with IDet under steady-state conditions compared with NPH (fluctuation(12-24 h) 1.27 +/- 0.17 vs. 1.56 +/- 0.72, P < 0.05). The overall
metabolic effect of IDet at steady state was comparable with that of NPH [GIR-area under curve (AUC)(0-24 h): 5697 +/- 1861 vs. 5929 +/- 1965 mg/kg] whereas a significantly lower effect (5187 +/- 1784 mg/kg, P = 0.01 vs. steady state) was observed following the first two IDet injections. GIR values at the end of clamp day 2 (first doses) and clamp day 3 (steady state) were comparable [GIR(trough 24 h) 3.7 +/- 1.7 vs. 3.8 +/- 1.6 mg/(kg x min) NS], indicating that IDet had reached steady state after the first two injections. CONCLUSIONS: IDet administered twice daily reached steady state after the second injection and showed a constant
metabolic effect over time under steady-state conditions. This should facilitate basal
insulin substitution and decrease the risk of
hypoglycaemia in insulin-treated subjects.
