Diabetes Research Group, Institute of Life Sciences College of Medicine, Swansea University, Singleton Park, Swansea SA2 8PP, UK.
Diabetes Metab. 2013 Dec;39(6):485-96. doi: 10.1016/j.diabet.2013.09.004. Epub 2013 Oct 22.
Metabolic consequences of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are the result of enhanced glucose-stimulated insulin secretion, inhibition of glucagon release, delayed gastric emptying and increased satiety. These attributes make GLP-1 agonists a treatment option in type 2 diabetes mellitus (T2DM). To optimise treatment choice, a detailed understanding of the effects of GLP-1 RAs on glucose homeostasis in individuals with T2DM is necessary. Although the various GLP-1 RAs share the same basic mechanisms of action, differences in pharmacokinetic/pharmacodynamic characteristics translate into differential effects on parameters of glycaemia. Head-to-head comparisons between long-acting non-prandial (liraglutide once daily and exenatide once weekly) and shorter-acting prandial (exenatide twice daily and lixisenatide once daily prandial) GLP-1 RAs confirm their differential effects on fasting plasma glucose (FPG) and post-prandial glucose (PPG). Liraglutide once daily and exenatide once weekly demonstrate greater reductions in FPG but lesser impacts on PPG excursions plasma than exenatide twice daily. Prandial GLP-1 RAs have a profound effect on post-prandial glycaemia, mediated by delaying gastric emptying, which is not subject to the tachyphylaxis occurring due to the sustained elevated plasma GLP-1 concentrations after treatment with long-acting GLP-1 RAs. Lixisenatide once-daily prandial, in contrast to liraglutide, strongly suppresses post-prandial glucagon secretion, further contributing to the more pronounced PPG-lowering effect found with lixisenatide. Evidence suggests that the GLP-1 RAs that predominantly target the prandial glucose excursions, such as exenatide twice daily and lixisenatide once-daily prandial, are therefore best used as combination therapy with basal insulin and will form an important new treatment option for individuals with T2DM.
胰高血糖素样肽-1 受体激动剂（GLP-1 RAs）的代谢作用是由于增强了葡萄糖刺激的胰岛素分泌、抑制了胰高血糖素的释放、延缓了胃排空和增加了饱腹感。这些特性使 GLP-1 激动剂成为 2 型糖尿病（T2DM）的治疗选择。为了优化治疗选择，需要详细了解 GLP-1 RA 在 T2DM 个体中对葡萄糖稳态的影响。虽然各种 GLP-1 RAs 具有相同的基本作用机制，但药代动力学/药效学特征的差异会导致对血糖参数的不同影响。长效非餐时（每日一次利拉鲁肽和每周一次艾塞那肽）和短效餐时（每日两次艾塞那肽和每日一次餐前利西那肽）GLP-1 RAs 的头对头比较证实了它们对空腹血糖（FPG）和餐后血糖（PPG）的不同影响。每日一次利拉鲁肽和每周一次艾塞那肽对 FPG 的降低作用更大，但对 PPG 波动的影响较小，而每日两次艾塞那肽则更小。餐时 GLP-1 RAs 通过延迟胃排空对餐后血糖产生深远影响，这不受长效 GLP-1 RAs 治疗后由于持续升高的血浆 GLP-1 浓度而发生的脱敏作用的影响。与利拉鲁肽不同，每日一次餐前利西那肽强烈抑制餐后胰高血糖素分泌，进一步导致利西那肽对 PPG 降低作用更明显。有证据表明，主要针对餐后血糖波动的 GLP-1 RAs，如每日两次艾塞那肽和每日一次餐前利西那肽，因此最好与基础胰岛素联合作为联合治疗，将成为 T2DM 患者的一种重要新治疗选择。
