Chiu Wei-Yih, Shih Shyang-Rong, Tseng Chin-Hsiao
Department of Internal Medicine, National Taiwan University College of Medicine, Taipei 10002, Taiwan.
Exp Diabetes Res. 2012;2012:924168. doi: 10.1155/2012/924168. Epub 2012 May 28.
There is a concern on the risk of thyroid cancer associated with glucagon-like peptide-1 (GLP-1) analogs including liraglutide and exenatide. In this article, we review related experimental studies, clinical trials and observational human studies currently available. In rodents, liraglutide activated the GLP-1 receptors on C-cells, causing an increased incidence of C-cell neoplasia. Animal experiments with monkeys demonstrated no increase in calcitonin release and no C-cell proliferation after long-term liraglutide administration. Longitudinal 2-year data from clinical trials do not support any significant risk for the activation or growth of C-cell cancer in humans in response to liraglutide. However, an analysis of the FDA adverse event reporting system database suggested an increased risk for thyroid cancer associated with exenatide after its marketing. Noticeably, a recent study discovered that GLP-1 receptor could also be expressed in human papillary thyroid carcinomas (PTC), but the impact of GLP-1 analogs on PTC is not known. Therefore, GLP-1 analogs might increase the risk of thyroid C-cell pathology in rodents, but its risk in humans awaits confirmation. Since GLP-1 receptor is also expressed in PTC besides C-cells, it is important to investigate the actions of GLP-1 on different subtypes of thyroid cancer in the future.
人们担心胰高血糖素样肽-1（GLP-1）类似物（包括利拉鲁肽和艾塞那肽）与甲状腺癌风险有关。在本文中，我们回顾了目前可用的相关实验研究、临床试验和人类观察性研究。在啮齿动物中，利拉鲁肽激活了C细胞上的GLP-1受体，导致C细胞瘤变的发生率增加。对猴子进行的动物实验表明，长期给予利拉鲁肽后，降钙素释放没有增加，C细胞也没有增殖。临床试验的两年纵向数据不支持利拉鲁肽会使人类C细胞癌激活或生长的任何显著风险。然而，对美国食品药品监督管理局（FDA）不良事件报告系统数据库的分析表明，艾塞那肽上市后与甲状腺癌风险增加有关。值得注意的是，最近一项研究发现GLP-1受体也可在人甲状腺乳头状癌（PTC）中表达，但GLP-1类似物对PTC的影响尚不清楚。因此，GLP-1类似物可能会增加啮齿动物甲状腺C细胞病变的风险，但其在人类中的风险有待证实。由于除了C细胞外，GLP-1受体在PTC中也有表达，未来研究GLP-1对不同亚型甲状腺癌的作用很重要。
