Vajo Z, Duckworth W C
Section of Endocrinology, Veterans Affairs Medical Center, Phoenix, Arizona 85012, USA.
Pharmacol Rev. 2000 Mar;52(1):1-9.
Tight glucose control is essential to minimize complications in diabetic patients. However, the pharmacokinetic characteristics of the currently available rapid-, intermediate-, and long-acting preparations of human insulin make it almost impossible to achieve sustained normoglycemia. Until recently, improvements in insulin formulations were seriously limited as advances were only achieved in insulin purity, species, and characteristics of the retarding agent. The availability of molecular genetic techniques opened new windows to create insulin analogs by changing the structure of the native protein and to improve the therapeutic properties. The first clinically available insulin analog, Lispro, confirmed the hopes by showing that improved glycemic control can be achieved without an increase in hypoglycemic events. This requires, however, optimal basal insulin replacement, either by multiple daily injections of neutral protein Hagedorn (NPH) insulin or by insulin pump. Evidence suggests that short-acting insulin analogs would be better matched by a true basal insulin than by the erratically absorbed and rather short-acting NPH insulin. Therefore, future availability of long-acting analogs raises the hope to realize the true potential benefits of the currently available short-acting analog, Lispro, and of those still awaiting approval. The introduction of new short-acting and the first truly long-acting analogs, the development of analogs with increased stability, less variability and perhaps selective action will help to develop more individualized treatment strategies targeted to specific patient characteristics and to achieve further improvements in glycemic control.
严格控制血糖对于将糖尿病患者的并发症降至最低至关重要。然而，目前可用的速效、中效和长效人胰岛素制剂的药代动力学特性使得几乎不可能实现持续的血糖正常。直到最近，胰岛素制剂的改进受到严重限制，因为进展仅体现在胰岛素纯度、种类以及阻滞剂特性方面。分子遗传学技术的出现为通过改变天然蛋白质结构来制造胰岛素类似物并改善治疗特性打开了新的窗口。首个临床可用的胰岛素类似物赖脯胰岛素证实了人们的期望，即可以在不增加低血糖事件的情况下实现更好的血糖控制。然而，这需要通过每日多次注射中性鱼精蛋白锌胰岛素（NPH）或胰岛素泵来进行最佳的基础胰岛素替代。有证据表明，与吸收不稳定且作用时间较短的NPH胰岛素相比，短效胰岛素类似物与真正的基础胰岛素更匹配。因此，长效类似物的未来可用性增加了实现当前可用的短效类似物赖脯胰岛素以及那些仍在等待批准的类似物真正潜在益处的希望。新型短效和首个真正长效类似物的推出，具有更高稳定性、更低变异性以及可能具有选择性作用的类似物的开发，将有助于制定更具个性化的治疗策略，针对特定患者特征，并进一步改善血糖控制。
