Insulin detemir, does a new century bring a better basal insulin?

Abstract

The treatment of diabetes was revolutionised shortly after the turn of the twentieth century by the extraction and purification of insulin. Methods to protract (i.e. prolong) the action of insulin were developed in the 1930s; little changed in the technology of insulin protraction until the turn of this century when, with renewed interest in the importance of basal insulin in controlling diabetes and thus preventing or delaying complications, technology advanced again. Two new long-acting insulin analogues have come to the market; some may be familiar with insulin glargine, which has been widely used for some years now. This review attempts to describe the novel method of protraction that insulin detemir (launched last summer) employs by albumin binding, to discuss the possible therapeutic benefits of this method of protraction and to describe the findings of studies comparing insulin detemir with other currently available long-acting insulin preparations. The intention of this article is not to review all of the currently available long-acting insulin analogues.

Consequences of Weight Gain Associated With Insulin Therapy in Adolescents

“…This finding is in contrast to NPH insulin, which was associated with weight gain of 0.7 to 0.8 kg over 6 months [41][42][43][44][45] 48 There was also a risk reduction for nocturnal hypoglycemia of some 50% with insulin detemir in this study. It is possible that the reduced risk of weight gain with insulin detemir might relate to the risk reduction for hypoglycemia, but other mechanisms, including a reduced ratio of peripheral:hepatic action 49 and a central effect on appetite, 50 have been suggested.…”

Long-acting insulin analogues elicit atypical signalling events mediated by the insulin receptor and insulin-like growth factor-I receptor

“…Longacting insulin analogue insulin detemir (B29Lys[ε-tetradecanoyl],desB30 human insulin), on the other hand, was generated by omitting a threonine residue at position B30 and by acylation of a lysine residue at position B29 with myristic acid, a C14 fatty acid chain. Insulin detemir binds in the blood to albumin via its fatty acid moiety [6]. The major protraction occurs via albumin binding and stabilisation of the hexamer by myristic acid in the subcutis at the injection depot, a process that results in delayed absorption.…”

Insulin detemir: A new option for the treatment of diabetes

“…The addition of the fatty acid chain on insulin detemir promotes increased self‐association of insulin detemir molecules and allows for the reversible binding of insulin detemir to albumin at the injection site, contributing to its novel mechanism for protracted action (Chapman & Perry, 2004; Novo Nordisk, 2005). Insulin detemir molecules can readily enter the circulation, where they again reversibly bind albumin, further delaying distribution to target tissues (Hordern & Russell‐Jones, 2005).…”

“…The lack of weight gain with insulin detemir may be, in part, because of decreased within‐patient variability and a reduction in the perceived risk of hypoglycemia (Haak et al; Russell‐Jones et al). However, the mechanisms behind the favorable weight effects of insulin detemir are not fully understood and are still being investigated (Hennige et al, 2006; Hordern & Russell‐Jones, 2005).…”