Exenatide: An incretin mimetic for the treatment of type 2 diabetes mellitus
Exenatide: An incretin mimetic for the treatment of type 2 diabetes mellitus
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DOI：
10.1016/j.clinthera.2006.05.006
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发表时间：
2006-05-01
影响因子：
3.2
通讯作者：
Campbell, R. Keith
中科院分区：
文献类型：
--
作者：
Iltz, Jason L.;Baker, Danial E.;Campbell, R. Keith
背景：艾塞那肽是一种皮下注射的肠促胰岛素模拟物。二甲双胍是一种磺酰脲类药物，可作为改善2型糖尿病（T2 DM）患者血糖控制的辅助治疗，这些患者已接受二甲双胍、磺酰脲类药物或两者联合治疗，但血糖控制仍不佳。目的：本文综述了现有的临床药理学信息，比较疗效，耐受性，药物相互作用，禁忌症和注意事项，剂量和管理，可用性和储存，方法：检索MEDLINE（1966年-2006年4月）和Web of Science（1995年-2006年4月），查找以英文发表的原始研究和综述文章。使用的检索词为艾塞那肽、艾塞那肽-4、胰高血糖素样肽-1、GLP-1和肠促胰岛素模拟物。还查阅了已识别文章的参考文献列表，以及从药品说明书中选择的信息。所有相关的比较疗效的研究，可在出版的形式被列入review.Results：天然存在的肠促胰岛素，如胰高血糖素样肽-1（GLP-1），表现出促胰岛素释放后，从肠道进入循环的特性。作为GLP-1激动剂，艾塞那肽通过模拟天然存在的GLP-1的作用来改善葡萄糖稳态。它通过结合已知机制降低空腹和餐后葡萄糖浓度来改善血糖控制，包括葡萄糖依赖性胰岛素分泌、恢复第一时相胰岛素反应、调节胰高血糖素分泌、延迟胃排空和减少食物摄入。确定了三项III期疗效比较试验，共招募了1446例患者，这些患者在现有二甲双胍、磺脲类药物或两者联合治疗的基础上接受艾塞那肽5 μ g SC BID、艾塞那肽10 μ g SC BID或安慰剂治疗30周。在这些试验中，艾塞那肽的添加与糖化血红蛋白（HbA（1c））值的显著降低相关（P < 0.001- P < 0.002），在接受艾塞那肽治疗的患者中，达到HbA（1c）10%的患者中，低血糖的比例更高结论：在临床试验期间，艾塞那肽加用现有的二甲双胍和/或磺脲类药物治疗T2 DM患者，可降低空腹和餐后血糖浓度，改善HbA（1c）和适度体重减轻。艾塞那肽治疗的主要不良反应是恶心。
Background: Exenatide is a subcutaneously injected incretin mimetic. It is indicated as adjunctive therapy to improve glycemic control in patients with type 2 diabetes mellitus (T2DM) who are already receiving therapy with metformin, a sulfonylurea, or both but continue to have suboptimal glycemic control.Objective: This article reviews available information on the clinical pharmacology, comparative efficacy, tolerability, drug interactions, contraindications and precautions, dosage and administration, availability and storage, and cost of exenatide.Methods: MEDLINE (1966-April 2006) and Web of Science (1995-April 2006) were searched for original research and review articles published in the English language. The search terms used were exenatide, exendin-4, glucagon-like peptide-1, GLP-1, and incretin mimetic. The reference lists of identified articles were also consulted, as was selected information from the package insert for exenatide. All relevant comparative efficacy studies that were available in published form were included in the review.Results: Naturally occurring incretins, such as glucagon-like peptide-1 (GLP-1), exhibit insulinotropic properties after release into the circulation from the gut. As a GLP-1 agonist, exenatide improves glucose homeostasis by mimicking the actions of naturally occurring GLP-1. It improves glycemic control by reducing fasting and postprandial glucose concentrations through a combination of known mechanisms, including glucose-dependent insulin secretion, restoration of first-phase insulin response, regulation of glucagon secretion, delaying gastric emptying, and decreasing food intake. Three Phase III comparative efficacy trials were identified that enrolled a total of 1446 patients who received exenatide 5 mu g SC BID, exenatide 10 mu g SC BID, or placebo for 30 weeks in addition to their existing therapy with metformin, sulfonylurea, or both. In these trials, the addition of exenatide was associated with significant reductions in glycosylated hemoglobin (HbA(1c)) values (P < 0.001- P < 0.002), greater proportions of patients achieving an HbA(1c) 10% of patients receiving exenatide were hypoglycemia (19.6%), diarrhea (12.8%), and vomiting (12.8%).Conclusions: During clinical trials, exenatide added to existing metformin and/or sulfonylurea therapy in patients with T2DM reduced fasting and postprandial glucose concentrations, with improvements in HbA(1c) and modest weight loss. The main adverse effect associated with exenatide therapy was nausea.