Loma Linda University School of Medicine, Loma Linda, USA.
Diabetes Ther. 2011 Mar;2(1):29-39. doi: 10.1007/s13300-010-0013-5. Epub 2011 Jan 18.
Glucagon-like peptide-1 (GLP-1) has been the focus of considerable research activity in the treatment of type 2 diabetes mellitus (T2DM) because the incretin effect is significantly reduced or absent in individuals with T2DM. Thus, pharmacologic efforts to develop medications that mimic the actions of GLP-1 have become a target for improving or reversing chronic hyperglycemia. Two GLP-1 receptor agonists are commercially available: exenatide twice daily (b.i.d.) and liraglutide once daily (q.d.). Targeted and individualized intensification of diabetes management can best be accomplished with a thorough understanding of these new medications.
Information was gathered through a search of MEDLINE and PubMed for GLP-1 and glycemic management in patients with type 2 diabetes.
Activation of the GLP-1 receptors on the β-cells results in enhanced levels of insulin biosynthesis, β-cell proliferation, resistance to β-cell apoptosis, and enhanced β-cell survival in both humans and rodents; yet, the risk of hypoglycemia is minimized because insulin production and exocytosis occurs in a glucose-dependent manner. The efficacy and safety of the two commercially available GLP-1 receptor agonists, liraglutide and exenatide, in managing postprandial glycemia have been well documented in numerous clinical trials, in which reductions in glycosylated hemoglobin (HbA1c) levels of -0.79% to -1.12% have been demonstrated. Weight reduction/maintenance and improvements in blood pressure and lipidemia have also been reported.
Because GLP-1 receptor agonists work in a glucose-dependent manner, they are likely to reduce hyperglycemia safely, without a marked fluctuation toward hypoglycemia. In the process of acutely restoring β-cell function, GLP-1 agonists may allow patients to achieve HbA(1c) <7% without experiencing weight gain or hypoglycemia. The ability of GLP-1 receptor agonists to improve blood pressure and postprandial lipidemia in the context of weight neutrality or weight loss may have the potential to ameliorate some of the cardiovascular risks observed in patients with T2DM.
胰高血糖素样肽-1（GLP-1）在 2 型糖尿病（T2DM）的治疗中受到了相当多的研究关注，因为 T2DM 患者的肠促胰岛素效应显著降低或缺失。因此，开发模仿 GLP-1 作用的药物已成为改善或逆转慢性高血糖的目标。目前有两种 GLP-1 受体激动剂可供临床使用：每日两次给予艾塞那肽（b.i.d.）和每日一次给予利拉鲁肽（q.d.）。只有充分了解这些新药，才能对糖尿病进行有针对性和个体化的强化治疗。
通过在 MEDLINE 和 PubMed 上搜索 GLP-1 和 2 型糖尿病患者的血糖管理相关信息，收集资料。
激活β细胞上的 GLP-1 受体可增强胰岛素生物合成、β细胞增殖、抵抗β细胞凋亡和β细胞存活，在人类和啮齿动物中均如此；然而，由于胰岛素的产生和分泌呈葡萄糖依赖性，低血糖的风险最小化。两种已上市的 GLP-1 受体激动剂，即利拉鲁肽和艾塞那肽，在控制餐后血糖方面的疗效和安全性已在大量临床试验中得到充分证实，这些试验显示糖化血红蛋白（HbA1c）水平降低了 0.79%~1.12%。体重减轻/维持以及血压和血脂的改善也有报道。
由于 GLP-1 受体激动剂呈葡萄糖依赖性作用，因此它们可能在不引起明显低血糖波动的情况下安全地降低高血糖。在急性恢复β细胞功能的过程中，GLP-1 激动剂可能使患者的 HbA1c ＜7%，而不会发生体重增加或低血糖。GLP-1 受体激动剂在体重中性或减轻的情况下改善血压和餐后血脂的能力，可能有潜力改善 T2DM 患者观察到的一些心血管风险。
