An overview of once-weekly glucagon-like peptide-1 receptor agonists-available efficacy and safety data and perspectives for the future
An overview of once-weekly glucagon-like peptide-1 receptor agonists-available efficacy and safety data and perspectives for the future
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DOI：
10.1111/j.1463-1326.2011.01357.x
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发表时间：
2011-05-01
影响因子：
5.8
通讯作者：
Holst, J. J.
中科院分区：
文献类型：
--
作者：
Madsbad, S.;Kielgast, U.;Holst, J. J.
基于肠降血糖素的治疗，如注射用胰高血糖素样肽-1（GLP-1）受体激动剂和口服二肽基肽酶-4（DPP-4）抑制剂，最近已被引入临床实践。目前，GLP-1受体激动剂需要每天给药一次或两次。几种每周一次的GLP-1受体激动剂处于III期开发阶段。本综述检查了每周一次GLP-1受体激动剂的疗效、安全性和未来前景：艾塞那肽每周一次、他司鲁肽、阿必鲁肽、LY 2189265和CJC-1134-PC，并将其与目前可用的激动剂艾塞那肽BID和利拉鲁肽QD进行了比较。与艾塞那肽BID相比，每周一次GLP-1受体激动剂可使血红蛋白A1 c（HbA 1c）和空腹血糖降低更大，而每周一次GLP-1受体激动剂对餐后高血糖的影响较小。在大多数研究中，HbA 1c的降低幅度大于口服降糖药和甘精胰岛素。短效和长效激动剂之间的体重减轻没有差异。与艾塞那肽BID相比，每周一次激动剂的胃肠道副作用较少，但他司鲁肽除外。抗体似乎是最常见的每周一次艾塞那肽，而超敏反应已在少数患者接受他司鲁肽治疗。注射部位反应在长效GLP-1受体激动剂之间存在差异，并且比艾塞那肽BID和利拉鲁肽更常见。在人类中，没有发现表明每周一次激动剂与C细胞癌之间存在关联的信号。心血管安全性、血糖控制的持久性和对体重的影响将从几项正在进行的主要长期试验中显现出来。每周一次的GLP-1受体类似物是治疗2型糖尿病的有希望的候选药物，尽管其疗效可能不上级每日一次的类似物利拉鲁肽。
Incretin-based therapies, such as the injectable glucagon-like peptide-1 (GLP-1) receptor agonists and orally administered dipeptidyl peptidase-4 (DPP-4) inhibitors, have recently been introduced into clinical practice. At present, the GLP-1 receptor agonists need to be administered once or twice daily. Several once-weekly GLP-1 receptor agonists are in phase 3 development. This review examines the efficacy, safety and perspective for the future of the once-weekly GLP-1 receptor agonists: exenatide once weekly, taspoglutide, albiglutide, LY2189265 and CJC-1134-PC, and compared them to the currently available agonists, exenatide BID and liraglutide QD. A greater reduction in haemoglobin A1c (HbA1c) and fasting plasma glucose was found with the once-weekly GLP-1 receptor agonists compared with exenatide BID, while the effect on postprandial hyperglycaemia was modest with the once-weekly GLP-1 receptor agonist. The reduction in HbA1c was in most studies greater compared to oral antidiabetic drugs and insulin glargine. The reduction in weight did not differ between the short- and long-acting agonists. The gastrointestinal side effects were less with the once-weekly agonists compared with exenatide BID, except for taspoglutide. Antibodies seem to be most frequent with exenatide once weekly, while hypersensitivity has been described in few patients treated with taspoglutide. Injection site reactions differ among the long-acting GLP-1 receptor agonists and are observed more frequently than with exenatide BID and liraglutide. In humans, no signal has been found indicating an association between the once-weekly agonists and C-cell cancer. The cardiovascular safety, durability of glucose control and effect on weight will emerge from several ongoing major long-term trials. The once-weekly GLP-1 receptor analogues are promising candidates for the treatment of type 2 diabetes, although their efficacy may not be superior to once-daily analogue liraglutide.