Clinical Efficacy and Safety of Once-Weekly Glucagon-Like Peptide-1 Agonists in Development for Treatment of Type 2 Diabetes Mellitus in Adults
Clinical Efficacy and Safety of Once-Weekly Glucagon-Like Peptide-1 Agonists in Development for Treatment of Type 2 Diabetes Mellitus in Adults
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DOI：
10.1345/aph.1q379
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发表时间：
2012-01-01
影响因子：
2.9
通讯作者：
Brackett, Adriane
中科院分区：
文献类型：
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作者：
Tzefos, Maria;Harris, Kira;Brackett, Adriane
目的：应用计算机检索MEDLINE数据库(1966-2011-08)，检索词：2型糖尿病、胰升糖素样肽-1激动剂、胰升糖素样肽-1激动剂、艾塞那肽长效释放片(LAR)、阿尔比鲁肽、他泊洛肽治疗2型糖尿病的药理、药代动力学、疗效及安全性。资料来源：应用计算机检索MEDLINE(1966-2011-08)，检索词：2型糖尿病、胰升糖素样肽-1激动剂、胰升糖素样肽-1激动剂、埃塞那替德长效缓释剂、丙二醛、他泊谷氨酸。DATA合成：在健康人中，天然的GLP-1增加了依赖葡萄糖的胰岛素的分泌，减少了胰高血糖素的分泌，并减缓了胃排空，但这些作用在T2 DM患者中可能会减弱。因为天然的GLP-1会被二肽基肽酶-IV迅速降解，所以它不是一个实用的治疗方案。目前，美国食品和药物管理局已经批准了两种GLP-1受体激动剂：艾塞那肽每天两次，利拉鲁肽每天一次。其他几种GLP-1激动剂，包括埃克塞那肽LAR、阿尔比路肽和他泊洛肽，正处于不同的临床试验阶段，并已被修改以延长其半衰期。这些药物已经显示出显著的改善血红蛋白A(1c)、空腹血糖和餐后血糖，以及体重、血压和血脂参数的改善。与一些现有的药物相比，这些药物可以减少给药计划的频率，改善全天的血糖控制，并提高治疗满意度。GLP-1激动剂耐受性良好，最常见的不良反应是与胃肠道相关的，在治疗早期发生，但通常在4-8周后消失。结论：每周一次的GLP-1激动剂在减轻体重方面提供了类似的血糖控制，并且总体上对患者的治疗满意度更高，因为它们易于使用，与一些可用的药物相比，需要较少的频繁剂量。
OBJECTIVE: To review pharmacologic, pharmacokinetic, efficacy, and safety data of once-weekly glucagon-like peptide-1 (GLP-1) agonists exenatide long-acting release (LAR), albiglutide, and taspoglutide in treatment of type 2 diabetes mellitus (T2DM).DATA SOURCES: A MEDLINE search (1966-August 2011) was conducted using the following key words: type 2 diabetes mellitus, glucagon-like peptide-1 agonists once weekly, glucagon-like peptide-1 agonists, exenatide LAR, albiglutide, and taspoglutide.STUDY SELECTION AND DATA EXTRACTION: All articles published in English identified from the data sources were evaluated, prioritizing randomized controlled trials with human data. The references of published articles identified were examined for additional studies appropriate for the review.DATA SYNTHESIS: Native GLP-1 increases glucose-dependent insulin secretion, decreases glucagon secretion, and slows gastric emptying in healthy individuals, but these effects may be blunted in patients with T2DM. Because native GLP-1 is rapidly degraded by dipeptidyl peptidase-IV, it is not a practical treatment option. Currently, 2 GLP-1 receptor agonists have been approved by the Food and Drug Administration: exenatide twice daily and liraglutide once daily. Several additional GLP-1 agonists, including exenatide LAR, albiglutide, and taspoglutide, are in various stages of clinical trials and have been modified to increase their half-lives. These agents have shown significant improvements in hemoglobin A(1c), fasting plasma glucose, and postprandial plasma glucose, as well as improvements in body weight, blood pressure, and lipid parameters. These agents allow for less-frequent dosing schedules, improved glycemic control throughout the day, and improved treatment satisfaction compared to some available agents. GLP-1 agonists have been well tolerated, with the most common adverse effects being gastrointestinal related, which occurred early in therapy but typically resolved after 4-8 weeks. The incidence of hypoglycemia was infrequent and mild during therapy.CONCLUSIONS: Once-weekly GLP-1 agonists provide similar glycemic control with weight reduction, as well as overall higher treatment satisfaction for patients because of their ease of use and need for less-frequent dosing compared to some available agents.