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The continuing quest for better subcutaneously administered prandial insulins: a review of recent developments and potential clinical implications.
Diabetes, Obesity and Metabolism ( IF 5.8 ) Pub Date : 2020-02-03 , DOI: 10.1111/dom.13963
David R Owens 1 , Geremia B Bolli 2
Affiliation  

The class of rapid-acting insulin analogues were introduced more than 20 years ago to control postprandial plasma glucose (PPG) excursions better than unmodified regular human insulin. Insulins, lispro, aspart and glulisine all achieved an earlier onset of action, greater peak effect and shorter duration of action resulting in lower PPG levels and a reduced risk of late postprandial hypoglycaemia. However, the subcutaneous absorption rate of these analogues still fails to match the physiological profile of insulin in the systemic circulation following a meal. Recent reformulations of aspart and lispro have generated a second generation of more rapid-acting insulin analogue candidates, including fast-acting aspart (faster aspart), ultra-rapid lispro and BioChaperone Lispro. These modifications have the potential to mimic physiological prandial insulin secretion better with an even earlier onset of action with improved PPG control, shorter duration of effect and reduced risk of hypoglycaemia. Recent phase 3 trials in type 1 and type 2 diabetes show that faster aspart and ultra-rapid lispro compared with conventional aspart and lispro, achieved fewer PPG excursions with a small increase in post-meal hypoglycaemia but similar or marginally superior glycated haemoglobin levels, and suggest the need for parallel optimization of basal insulin replacement. Phase 1 trials for BioChaperone Lispro are equally encouraging with phase 3 trials yet to be initiated. Comparative analysis of the clinical and pharmacological evidence for these new prandial insulin candidates in the treatment of type 1 and type 2 diabetes is the main focus of this review.

中文翻译:

持续寻求更好的皮下注射膳食胰岛素的方法:最新进展及其潜在临床意义的综述。

与未经修饰的普通人胰岛素相比,该类速效胰岛素类似物已于20多年前推出,以更好地控制餐后血浆葡萄糖(PPG)偏移。胰岛素,赖脯胰岛素,天冬氨酸和草甘膦都可以更早地起效,峰值作用更大,作用时间更短,从而降低PPG水平并降低餐后低血糖的风险。然而,这些类似物的皮下吸收速率仍不能与餐后全身循环中胰岛素的生理特性相匹配。最近对aspart和lispro的重新配方产生了第二代更速效的胰岛素类似物候选物,包括速效的aspart(更快的aspart),超快的lispro和BioChaperone Lispro。这些修饰具有更好的模仿生理性胰岛素分泌的潜力,甚至可以更早地发挥作用,改善PPG的控制,缩短作用时间,降低低血糖的风险。最近在1型和2型糖尿病中进行的3期试验显示,与传统的aspart和lispro相比,更快的aspart和超快lispro可使PPG偏移减少,餐后低血糖增加较小,但糖化血红蛋白水平相似或略高,并且提示需要并行优化基础胰岛素替代。BioChaperone Lispro的1期试验同样令人鼓舞,但尚未启动3期试验。
更新日期:2020-02-03
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