Insulin detemir: A review

Abstract

Patients with diabetes are at increased risk of mortality and morbidity from micro- and macrovascular complications (1, 2). Landmark studies in type 1 and 2 diabetes have clearly shown that improved glycemic control leads to better outcomes (3-6). With the introduction of the General Medical Service contract, the England and Wales National Service Framework, and other schemes, there is a national drive to improve control in patients with diabetes. The treatment of diabetes was revolutionized shortly after the turn of the 20th century by the extraction and purification of insulin. Since methods to protract (i.e., prolong) the action of insulin were developed in the 1930s, little changed in this technology until the turn of this century. At this time there was renewed interest in the importance of basal insulin in controlling diabetes and thus preventing or delaying complications, and so technology advanced again. Two new basal insulin analogues have come to the market: insulin glargine, which has been widely used for some years now, and detemir. This review describes the novel method of protraction employed by insulin detemir, discusses the possible therapeutic benefits of this method of protraction, and describes the findings of studies comparing insulin detemir with other currently available basal insulin preparations. It is not the intention of this paper to be a review of all the currently available long-acting insulin analogues.

Reductive amination of ω-conotoxin MVIIA: synthesis, determination of modification sites, and self-assembly

“…For example, Detemir is a new insulin analog prepared by removing Thr from the B30 position of human insulin and attaching a myristic acid side chain to lysine at the B29 position. After subcutaneous injection, the myristic acid side chain can effectively promote the formation of insulin hexamer and reversible binding with HSA, thus slowing down the diffusion of insulin in vivo and making the drug release slow (Kurtzhals 2007 ; Hordern 2006 ; Home and Kurtzhals 2006 ). Liraglutide, used in the treatment of type 2 diabetes and obesity, replaces the lysine at position 34 of human glucagon-like peptide 1 (GLP-1) with Arg and introduces a Glu-mediated 16-carbon palmitic acid side chain at position 26 Lys, which can form colloidal cluster-like aggregates at the subcutaneous injection site and is chemically stable and less susceptible to degradation (Ladenheim 2015 ; Nuffer and Trujillo 2015 ; Jacobsen et al 2016 ; Iepsen et al 2015 ).…”

Human insulin A‐chain peptide analog(s) with in vitro biological activity

“…Myristic acid substitution). 10,11 These analogs are produced by genetic processing, a procedure which is rather long and expensive, with low and variable yield. To avoid these practical drawbacks, several approachs are currently in progress to produce insulin or insulin-derived peptides by combinatory-like chemistry or by chemical synthesis.…”