a Department of Medicine , University of Maryland School of Medicine , Baltimore , MD , USA.
Expert Opin Pharmacother. 2019 Feb;20(2):133-141. doi: 10.1080/14656566.2018.1552258. Epub 2018 Nov 30.
Glucagon-like peptide-1 (GLP-1) receptor agonists are highly potent antihyperglycemic drugs that impose low risk of hypoglycemia and also result in body weight reduction. Currently, all approved members of the class require administration by injection. Areas covered: This manuscript reviews oral semaglutide-an experimental GLP-1 receptor agonist in phase-3 clinical development. Available pharmacological and clinical data of the drug are reviewed, and important end-points described. Expert opinion: Oral peptide delivery has become possible with the discovery of absorption enhancers. The clinical development program of once-daily oral semaglutide has shown superiority in reducing glycosylated hemoglobin and body weight in comparison with placebo and active comparators (sitagliptin, liraglutide, and empagliflozin). Safety and tolerability of oral semaglutide is in line with injectable members of the class. Delayed gastric emptying, local increase in pH, and enhanced absorption do not seem to affect the exposure of a number of other oral drugs that have been tested (metformin, digoxin, oral contraceptive ethinylestradiol/levonorgestrel, lisinopril, warfarin, furosemide and rosuvastatin). Clinical questions for further investigation include the effectiveness and safety of oral semaglutide in cardiovascular indications.
胰高血糖素样肽-1（GLP-1）受体激动剂是高效的抗高血糖药物，低血糖风险低，还能减轻体重。目前，该类别中所有批准的成员都需要通过注射给药。
本文综述了处于 3 期临床开发阶段的实验性 GLP-1 受体激动剂口服司美格鲁肽。回顾了该药物的可用药理学和临床数据，并描述了重要的终点。
随着吸收增强剂的发现，口服肽类药物的递送成为可能。每日口服一次司美格鲁肽的临床开发项目显示，与安慰剂和活性对照药物（西格列汀、利拉鲁肽和恩格列净）相比，它在降低糖化血红蛋白和体重方面具有优越性。口服司美格鲁肽的安全性和耐受性与该类别中的注射用药物一致。胃排空延迟、局部 pH 值升高和吸收增强似乎不会影响其他一些已测试的口服药物（二甲双胍、地高辛、口服避孕药炔雌醇/左炔诺孕酮、赖诺普利、华法林、呋塞米和瑞舒伐他汀）的暴露。进一步研究的临床问题包括口服司美格鲁肽在心血管适应证中的有效性和安全性。
