首页|Ⅱ型糖尿病胰高血糖素样肽-1受体激动剂的研究进展

Ⅱ型糖尿病胰高血糖素样肽-1受体激动剂的研究进展

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如今,胰高血糖素样肽-1(GLP-1)受体激动剂已成为治疗Ⅱ型糖尿病的降糖药物.他们的发展源于这样的认识,即由胰岛素分泌受损和胰高血糖素分泌过多组成的联合胰岛功能障碍,是高血糖症的关键缺陷.GLP-1 被证明可以针对这些缺陷,在发现二肽基肽酶4可以使天然GLP-1 失活之后,已经开发了几种不同的肽基肽酶4 抗性GLP-1 受体激动剂.它们是属于皮下给药,但在分子结构、分子大小和药代动力学方面存在差异,后者允许每天两次、每天一次或每周一次的给药.已被证明可有效减少糖化血红蛋白和体重,并且是安全和高度耐受的.心血管结局试验表明它们是中性的或有益的.在临床范例中,GLP-1 受体激动剂被定位为单独使用二甲双胍或与口服药物联合使用.它们在与胰岛素结合时也很有效,并且已经开发出与长效胰岛素的固定剂量组合.最近的发展包括非常长的给药时间表和口服可用性.从1990 年代初首次证明GLP-1 的抗糖尿病作用到今天积累的大量数据,研究代表了一个成功和合理的发展,其特点是集中在Ⅱ型糖尿病的管理中建立这种疗法.在临床范例中,GLP-1 受体激动剂被定位为单独使用二甲双胍或与口服药物联合使用.
Research Progress of Glucagon-like Peptide-1 Receptor Agonists in Type Ⅱ Diabetes Mellitus
Today,glucagon-like peptide-1(GLP-1)receptor agonists are established glucose-lowering drugs used in the management of type 2 diabetes.Their development emerged from the understanding that a combined islet dysfunction comprising of impaired insulin secretion and exaggerated glucagon secretion is the key defect of hyperglycemia.GLP-1 was shown to target these defects,and after the discovery that dipeptidyl peptidase-4 inactivates native GLP-1,several different dipeptidyl peptidase-4-resistant GLP-1 receptor agonists have been developed.They are administered subcutaneously,but show differences in molecular structure,molecular size and pharmacokinetics,the latter allowing twice-daily,once-daily or once-weekly administration.They have been shown to be efficient in reducing both glycated hemoglobin and bodyweight,and to be safe and highly tolerable.Cardiovascular outcomes trials have shown them to be neutral or beneficial.GLP-1 receptor agonists are positioned as add-ons to metformin alone or in combination with oral agents in the clinical paradigm.They are also efficient when combined with insulin,and fixed dose combinations with long-acting insulin have been developed.Recent development includes a very long administration schedule and oral availability.The research from the first demonstration of the antidiabetic action of GLP-1 in the early 1990s to the enormously accumulated data today represents a successful and rational development,which has been characterized by focused perseverance to establish this therapy in the management of type 2 diabetes.

glucagon-like peptide-1treatmenttype Ⅱ diabetes mellitusinsulin

孙健民、段小群

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桂林医学院,广西 桂林 541000

胰高血糖素样肽-1 治疗 Ⅱ型糖尿病 胰岛素

2024

广东化工
广东省石油化工研究院

广东化工

影响因子:0.288
ISSN:1007-1865
年,卷(期):2024.51(3)
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