Home Philip, Kurtzhals Peter
School of Clinical Medical Sciences--Diabetes, University of Newcastle upon Tyne, Framlington Place, NE2 4HH, UK.
Expert Opin Pharmacother. 2006 Feb;7(3):325-43. doi: 10.1517/14656566.7.3.325.
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.
地特胰岛素（Levemir，诺和诺德公司）是一种新型的、经过生物工程改造的人胰岛素类似物，已成功开发用于临床糖尿病治疗，作为基础胰岛素。它独特的作用延长机制是通过酰化实现的，从而产生可逆的白蛋白结合和额外的自聚集，在一定程度上解决了先前皮下注射基础胰岛素的一个基本局限性，即不同注射之间个体内时间 - 作用曲线的高度变异性。在一系列研究中表征的地特胰岛素的药理学特征表明，它在临床环境中具有提供疗效和耐受性优势的潜力。与NPH（中性鱼精蛋白锌）胰岛素相比，这些优势随后在试验中得到了证实。尽管血糖控制目标与对照药物相同，但在地特胰岛素的III期开发项目中，其血糖控制水平总体上至少与NPH胰岛素一样好，变异性更低是一个一致的发现。这与夜间低血糖事件风险的持续降低相关，夜间低血糖事件与胰岛素治疗的基础成分密切相关。另一个一致的发现是体重增加的倾向显著降低。将地特胰岛素与速效胰岛素门冬胰岛素联合使用的全类似物方案表明，当临床上使用设计用于实现特定药代动力学特征的胰岛素时可获得潜在益处；血糖控制，包括低血糖控制，明显优于基于人胰岛素的餐时加基础胰岛素方案。因此，地特胰岛素是外源性胰岛素系列中的一个有价值的补充，因为它应能构建出具有良好疗效和耐受性结果的治疗方案。
