Department of Medicine, Samuel Lunenfeld Research Institute, Mt Sinai Hospital, University of Toronto, Toronto, Ontario, Canada.
J Clin Endocrinol Metab. 2011 Jul;96(7):2027-31. doi: 10.1210/jc.2011-0599.
Antidiabetic therapies based on potentiation of incretin action are now widely used; however, understanding of their long-term safety remains incomplete.
We searched articles in PubMed for data assessing the safety of incretin-based therapies.
Three major areas of interest are reviewed: incretin action in the cardiovascular system, pancreatitis, and cancer. Incretin therapies reduce weight gain, minimize hypoglycemia, decrease inflammation, and are cardioprotective in preclinical studies. However, data permitting conclusions about whether incretin therapies modify the development of cardiovascular events in humans are not available. Case reports link incretin therapies to pancreatitis, but retrospective case control studies do not associate pancreatitis with glucagon-like peptide-1 receptor (GLP-1R) agonists or dipeptidyl peptidase-4 inhibitors. Preclinical studies of pancreatitis have yielded conflicting results, and mechanisms linking incretin receptor activation to pancreatic inflammation have not yet been forthcoming. GLP-1R activation promotes C-cell hyperplasia and medullary thyroid cancer in rodents; however, long-term clinical studies of sufficient size and duration to permit conclusions regarding cancer and incretin therapeutics have not yet been completed.
The available data on incretin action and incidence of cardiovascular events, pancreatitis, or cancer are not yet sufficient or robust enough to permit firm conclusions regarding associations with incretin-based therapies in humans with diabetes. The forthcoming results of long-term cardiovascular safety studies should provide more conclusive information about the safety of GLP-1R agonists and dipeptidyl peptidase-4 inhibitors in diabetic patients.
基于肠促胰岛素作用增强的抗糖尿病疗法目前已广泛应用；然而，其长期安全性仍不完全清楚。
我们在 PubMed 中搜索了评估肠促胰岛素疗法安全性的数据。
综述了三个主要关注领域：肠促胰岛素在心血管系统、胰腺炎和癌症中的作用。肠促胰岛素疗法可减轻体重增加、最大限度地减少低血糖、减少炎症，并在临床前研究中具有心脏保护作用。然而，尚无数据可得出关于肠促胰岛素疗法是否可改变人类心血管事件发展的结论。病例报告将肠促胰岛素疗法与胰腺炎联系起来，但回顾性病例对照研究并未将胰腺炎与胰高血糖素样肽-1 受体（GLP-1R）激动剂或二肽基肽酶-4 抑制剂联系起来。胰腺炎的临床前研究结果相互矛盾，且将肠促胰岛素受体激活与胰腺炎症联系起来的机制尚未明确。GLP-1R 激活可促进啮齿动物 C 细胞增生和甲状腺髓样癌；然而，尚未完成足够大和持续时间足够长的可对癌症和肠促胰岛素治疗相关的长期临床研究。
关于肠促胰岛素作用和心血管事件、胰腺炎或癌症发生率的现有数据还不够充分或稳健，无法对糖尿病患者应用肠促胰岛素类药物的安全性得出明确结论。即将进行的长期心血管安全性研究结果应提供更明确的信息，了解 GLP-1R 激动剂和二肽基肽酶-4 抑制剂在糖尿病患者中的安全性。
