Insulin detemir: from concept to clinical experience

Abstract

Insulin detemir (Levemir®, Novo Nordisk) is a novel, biologically engineered analogue of human insulin that has been successfully developed for clinical use in diabetes as a basal insulin. Its unique mechanism of prolongation of action, achieved through acylation to give reversible albumin binding and additional self-association, goes some way to addressing one of the fundamental limitations of previously available, subcutaneously administered basal insulins, a high level of within-person variability in time–action profile from one injection to another. The pharmacological profile of insulin detemir, characterised in a series of studies, suggested it had the potential to offer efficacy and tolerability advantages in the clinical setting. Such advantages, in comparison to NPH (neutral protamine Hagedorn) insulin, have subsequently been illustrated in trials. Despite glucose control targets that are identical to comparators, insulin detemir achieved levels of glycaemic control that, overall, were at least as good as NPH insulin in the Phase III development programme, with lower variability being a consistent finding. This was associated with consistent risk reductions in nocturnal hypoglycaemic events, which are closely linked with the basal component of insulin therapy. Another consistent finding has been a significantly reduced propensity for weight gain. An all-analogue regimen combining insulin detemir with the rapid-acting insulin aspart illustrated the potential benefits achievable when insulins that are designed to achieve defined pharmacokinetic profiles are employed clinically; blood glucose control, including hypoglycaemia, was significantly superior to a human insulin-based mealtime plus basal regimen. Insulin detemir is, therefore, a valuable addition to the range of exogenous insulins, as it should enable treatment regimens to be constructed that offer good outcomes of efficacy and tolerability.

Keywords::

• efficacy
• insulin analogue
• insulin detemir
• pharmacokinetics

Acknowledgements and conflict of interest

Philip Home has advised Novo Nordisk on the development of insulin detemir, including for some of the studies described, and received research funding in that regard. Peter Kurtzhals works in drug discovery at Novo Nordisk where he has been extensively involved in the development of insulin detemir and its pharmacological characterisation in preclinical studies.