Muñoz-Garach Araceli, Molina-Vega María, Tinahones Francisco J
Department of Endocrinology and Nutrition, Virgen de la Victoria Universitary Hospital, Malaga, Spain.
Department of Endocrinology and Nutrition, IBIMA foundation, Malaga, Spain.
Diabetes Ther. 2017 Feb;8(1):9-22. doi: 10.1007/s13300-016-0214-7. Epub 2016 Nov 28.
Lack of control in diabetic patients has stimulated the development of new insulin analogues. One of these was basal insulin peglispro (BIL) or LY2605541; it had a large hydrodynamic size, flat pharmacokinetic profile, half life of 2-3 days and acted preferably in the liver.
We reviewed the recent literature examining the pharmacokinetics, pharmacodynamics, efficacy and safety of BIL treatment in type 2 diabetes patients.
The pharmacodynamic and pharmacokinetic outline of BIL seemed to have an advantage over neutral protamine Hagedorn and glargine insulins. Recently, phase 3 studies suggested BIL was superior to glargine in reducing glucose levels in type 1 and type 2 diabetes patients in addition to causing less weight gain. It showed a different hypoglycaemia rate profile depending on the study population, with less nocturnal hypoglycaemia compared to glargine. Unfortunately, it caused higher transaminase and triglyceride levels, which led the company to discontinue development. The decision came after it had been analysed by the regulatory authorities and other external experts concerning the worse liver profile data from the IMAGINE trials.
BIL was an adequate basal insulin analogue with interesting specific properties. Unfortunately the disadvantages as shown in the lipid values and liver function tests led to its failure.
糖尿病患者血糖控制不佳促使了新型胰岛素类似物的研发。其中一种是基础胰岛素聚乙二醇化赖脯胰岛素（BIL）或LY2605541；它具有较大的流体力学尺寸、平稳的药代动力学特征、2至3天的半衰期，且主要在肝脏发挥作用。
我们回顾了近期有关BIL治疗2型糖尿病患者的药代动力学、药效学、疗效和安全性的文献。
BIL的药效学和药代动力学概况似乎优于中性精蛋白锌胰岛素和甘精胰岛素。最近的3期研究表明，BIL在降低1型和2型糖尿病患者血糖水平方面优于甘精胰岛素，且体重增加较少。根据研究人群的不同，它显示出不同的低血糖发生率，与甘精胰岛素相比，夜间低血糖较少。不幸的是，它导致转氨酶和甘油三酯水平升高，这使得该公司停止了研发。这一决定是在监管机构和其他外部专家对IMAGINE试验中较差的肝脏数据进行分析之后做出的。
BIL是一种具有有趣特殊性质的合适基础胰岛素类似物。不幸的是，脂质值和肝功能测试中显示的缺点导致了它的失败。
