Brown Dominique Xavier, Butler Emma Louise, Evans Marc
Diabetes Department, University Hospital Llandough, Cardiff, UK.
Drug Des Devel Ther. 2013 Dec 13;8:25-38. doi: 10.2147/DDDT.S45108.
Many patients with type 2 diabetes mellitus do not achieve target glycosylated hemoglobin A1c levels despite optimally titrated basal insulin and satisfactory fasting plasma glucose levels. Current evidence suggests that HbA1c levels are dictated by both basal glucose and postprandial glucose levels. This has led to a consensus that postprandial glucose excursions contribute to poor glycemic control in these patients. Lixisenatide is a once-daily, prandial glucagon-like peptide 1 (GLP-1) receptor agonist with a four-fold affinity for the GLP-1 receptor compared with native GLP-1. Importantly, lixisenatide causes a significant delay in gastric emptying time, an important determinant of the once-daily dosing regimen. An exendin-4 mimetic with six lysine residues removed at the C-terminal, lixisenatide has pronounced postprandial glucose-lowering effects, making it a novel incretin agent for use in combination with optimally titrated basal insulin. Lixisenatide exerts profound effects on postprandial glucose through established mechanisms of glucose-dependent insulin secretion and glucagon suppression in combination with delayed gastric emptying. This review discusses the likely place that lixisenatide will occupy in clinical practice, given its profound effects on postprandial glucose and potential to reduce glycemic variability.
尽管基础胰岛素已进行了最佳滴定且空腹血糖水平令人满意，但许多2型糖尿病患者仍未达到糖化血红蛋白A1c的目标水平。目前的证据表明，糖化血红蛋白A1c水平受基础血糖和餐后血糖水平的共同影响。这已形成一种共识，即餐后血糖波动是导致这些患者血糖控制不佳的原因。利司那肽是一种每日一次的餐时胰高血糖素样肽1（GLP-1）受体激动剂，与天然GLP-1相比，它对GLP-1受体的亲和力高四倍。重要的是，利司那肽会使胃排空时间显著延迟，这是每日一次给药方案的一个重要决定因素。利司那肽是一种C末端去除了六个赖氨酸残基的艾塞那肽类似物，具有显著的餐后降糖作用，使其成为一种可与最佳滴定的基础胰岛素联合使用的新型肠促胰岛素药物。利司那肽通过葡萄糖依赖性胰岛素分泌和胰高血糖素抑制的既定机制，结合胃排空延迟，对餐后血糖产生深远影响。鉴于利司那肽对餐后血糖的深远影响以及降低血糖变异性的潜力，本综述讨论了其在临床实践中可能占据的地位。
