【medical-news】以肠降血糖素为基础的2型糖尿病治
CONTEXT: Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are incretins secreted from enteroendocrine cells post-prandially in part to regulate glucose homeostasis. Dysregulation of these hormones is evident in T2DM. Two new drug classes, exenatide (GLP-1 mimetic) and sitagliptin (dipeptidyl peptidase [DPP] 4 inhibitor) have been approved by regulatory agencies for treating T2DM. Liraglutide (GLP-1 mimetic) and vildagliptin (DPP 4 inhibitor) are expected to arrive on the market soon. EVIDENCE ACQUISITION: The background of incretin-based therapy and selected clinical trials of these four drugs are reviewed. A MEDLINE search was conducted for published articles using the key words incretin, GIP, GLP-1, exendin-4, exenatide, DPP 4, liraglutide, sitagliptin, and vildagliptin. EVIDENCE SYNTHESIS: Exenatide and liraglutide are injection-based. Three-year follow-up data on exenatide showed a sustained weight loss and HbA1c reduction of 1%. Nausea and vomiting are common. Results from phase 3 studies are pending on liraglutide. Sitagliptin and vildagliptin are orally active. In 26-week studies, sitagliptin educes HbA1c by 0.6-0.8% as monotherapy, by 1.8% as initial combination therapy with metformin, and by 0.7% as add-on therapy to metformin. Vildaglitpin monotherapy lowered HbA1c by 1.0-1.4% after 24 weeks. Their major side effects are urinary tract and nasopharyngeal infections and headaches. Exenatide and liraglutide cause weight loss while sitagliptin and vildagliptin do not. CONCLUSION: The availability of GLP-1 mimetics and DPP 4 inhibitors has increased our armamentarium for treating T2DM. Unresolved issues such as the effects of GLP-1 mimetics and DPP 4 inhibitors on beta cell mass, the mechanism by which GLP-1 mimetics lowers glucagon levels, and exactly how DPP 4 inhibitors lead to a decline in plasma glucose levels without an increase in insulin secretion, need further research.
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(GIP) are incretins secreted from enteroendocrine cells post-prandially in part to regulate glucose homeostasis. Dysregulation of these hormones is evident in T2DM. Two new drug classes, exenatide (GLP-1 mimetic) and sitagliptin (dipeptidyl peptidase [DPP] 4 inhibitor) have been approved by regulatory agencies for treating T2DM. Liraglutide (GLP-1 mimetic) and vildagliptin (DPP 4 inhibitor) are expected to arrive on the market soon. EVIDENCE ACQUISITION: The background of incretin-based therapy and selected clinical trials of these four drugs are reviewed. A MEDLINE search was conducted for published articles using the key words incretin, GIP, GLP-1, exendin-4, exenatide, DPP 4, liraglutide, sitagliptin, and vildagliptin. EVIDENCE SYNTHESIS: Exenatide and liraglutide are injection-based. Three-year follow-up data on exenatide showed a sustained weight loss and HbA1c reduction of 1%. Nausea and vomiting are common. Results from phase 3 studies are pending on liraglutide. Sitagliptin and vildagliptin are orally active. In 26-week studies, sitagliptin educes HbA1c by 0.6-0.8% as monotherapy, by 1.8% as initial combination therapy with metformin, and by 0.7% as add-on therapy to metformin. Vildaglitpin monotherapy lowered HbA1c by 1.0-1.4% after 24 weeks. Their major side effects are urinary tract and nasopharyngeal infections and headaches. Exenatide and liraglutide cause weight loss while sitagliptin and vildagliptin do not. CONCLUSION: The availability of GLP-1 mimetics and DPP 4 inhibitors has increased our armamentarium for treating T2DM. Unresolved issues such as the effects of GLP-1 mimetics and DPP 4 inhibitors on beta cell mass, the mechanism by which GLP-1 mimetics lowers glucagon levels, and exactly how DPP 4 inhibitors lead to a decline in plasma glucose levels without an increase in insulin secretion, need further research.
背景：胰高糖素样肽1(GLP-1)和糖依赖性胰岛素释放肽(GIP)是肠内分泌细胞分泌的肠促胰岛素，属于调节餐后糖平衡的一部分。T2DM患者的这些调节明显失调。两类新药exenatide(GIP-1类似物)和sitagliptin(二肽基肽酶 [DPP] 4 抑制剂) 用来治疗糖尿病已经被管理机构认可。Liraglutide(GIP-1类似物)和vildagliptin (DPP4 抑制剂)有望很快走向市场。
证据获得：我们回顾了肠促胰岛素为基础的治疗背景和一些有关这四种药物的临床试验。用肠促胰岛素、GIP、GLP-1、exendin-4、DPP4、liraglutide,、sitagliptin和vildagliptin作为关键词在MEDLINE搜索发表的文献。
证据综合：Exenatide 和liraglutide以注射剂为基础。exenatide 的3年随访数据显示有持续的体重减轻，HbA1c下降了1%。恶性和呕吐较常见。Liraglutide三阶段的研究结果尚未出来。Sitagliptin和vildagliptin口服是有效的。在26周的研究里，sitagliptin 单药治疗HbA1c降低了0.6-0.8%，一开始即联合二甲双胍是1.8%，二甲双胍基础上再加用则是0.7%。Vildaglitpin单药治疗24周后降低HbA1c 1.0-1.4%，主要的副作用是泌尿系统和鼻咽部感染以及头痛。Exenatide和liraglutide可以减轻体重， sitagliptin和vildagliptin则没有。
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作者:admin@医学,生命科学 2011-04-30 17:14
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