Pharmacodynamics of the long-acting insulin analogues detemir and glargine following single-doses and under steady-state conditions in patients with type 1 diabetes

Abstract

Aim: The pharmacodynamic characteristics of the basal insulin analogues insulin detemir (IDet) and insulin glargine (IGlar) have been examined extensively via euglycaemic clamp studies. However, differences in clamp methodology and in the analysis of clamp data between trials have led to confusion over the duration of action of these two insulins. The aim of this study was to address these ambiguities in the literature by assessing the pharmacodynamic properties of IDet and IGlar over 30 h under single-dose and steady-state conditions using the definitions and procedures previously standardized by Heise and Pieber in 2007.

Methods: This was a single-centre, randomized, double-blind, glucose clamp trial involving 36 patients with type 1 diabetes.

Results: The mean duration of action of IDet was 25.9 h, compared with 19.8 h for IGlar after a single-dose (NS), and 23.3 h (IDet) versus 27.1 h (IGlar) at steady-state (p < 0.0001). IDet had a significantly higher area under the curve glucose infusion rate (AUCGIR ) than IGlar over 0-12 h after a single-dose (p = 0.0018). The steady-state AUCGIR for IDet was numerically higher than IGlar over 0-12 h (728 vs. 592 mg/kg, respectively; p = NS), but significantly lower than IGlar at 12-30 h (p = 0.0003).

Conclusions: The duration of action of IDet is 23 h (range: 4.0-30.0), while that of IGlar is 27 h (range: 10.5-29.0) (95% CI: -8.1, 0.6). This suggests both insulins can be used for once-daily dosing, but individual needs must be considered.

Keywords: diabetes mellitus; insulin analogues; pharmacology; type 1 diabetes.