Article Summary A double-blind, randomized, dose-response study investigating the pharmacodynamic and pharmacokinetic properties of the long-acting insulin analog detemir. Plank J, Bodenlenz M, Sinner F, et al. Diabetes Care. 2005;28:1107-1112. Objective: To investigate the 24-hour pharmacodynamic (PD) profile, duration of action, and dose-response relationship for 5 doses of insulin detemir (0.1, 0.2, 0.4, 0.8, and 1.6 U/kg) and 1 dose of NPH insulin (0.3 IU/kg) in patients with type 1 diabetes. Methods: Single-center, double-blind, randomized, 6-period, dose-response, crossover trial. Patients were randomized to specific treatment sequences encompassing 5 doses of insulin detemir and 1 dose of NPH insulin. Assessments were carried out as a 24-hour isoglycemic clamp (7.2 mmol/L). The primary end point was duration of action, and the secondary end points were numerous PD and pharmacokinetic (PK) parameters. Blood samples for PK evaluations were drawn every hour. Results: Insulin detemir showed a clear dose-dependent effect with a duration of action of 5.7 hours at the lowest dose (0.1 U/kg) to 23.2 hours at the highest dose (1.6 U/kg). NPH insulin (0.3 IU/kg) had an estimated duration of action of 12.7 hours. The total and maximal insulin exposure for insulin detemir was clearly dose dependent. There was no clear dose dependency related to the time to maximal insulin exposure. Conclusion: Over a range of clinically relevant doses, insulin detemir showed a linear dose response and provided a flat and prolonged PD profile.