Neuville M F, Paquot N, Scheen A J
Service de Diabétologie, Nutrition et Maladies métaboliques, CHU Liège, Belgique.
Rev Med Liege. 2023 Jan;78(1):40-45.
Glucagon-like peptide-1 (GLP-1) receptor agonists have a privileged place in the management of type 2 diabetes (T2D). They not only improve glucose control without inducing hypoglycaemia and trigger weight loss, but also protect against atherosclerotic cardiovascular disease. Increasing the dose of three of them (liraglutide, semaglutide, dulaglutide) allows better glycaemic results and of potential interest a greater weight reduction. Liraglutide at a daily dose of 3.0 mg and semaglutide at a weekly dose of 2.4 mg received the indication for the therapy of obesity. A recent innovation consists in the development of dual unimolecular agonists that target GLP-1 and GIP («glucose-dependent insulinotropic polypeptide») receptors (tirzepatide) or GLP-1 and glucagon receptors (cotadutide). Tirzepatide, in the SURPASS programme, showed impressive reductions in glycated haemoglobin level and body weight, greater than those observed with dulaglutide or semaglutide. Tirzepatide received the indication of the treatment of T2D and is currently tested in obesity (SURMOUNT programme). Interestingly, triagonists GIP/GLP-1/glucagon are currently developed for the management of T2D and obesity, with also perspectives for treating metabolic-associated fatty liver disease.
胰高血糖素样肽-1（GLP-1）受体激动剂在2型糖尿病（T2D）的管理中占据重要地位。它们不仅能在不引起低血糖的情况下改善血糖控制并促使体重减轻，还能预防动脉粥样硬化性心血管疾病。增加其中三种药物（利拉鲁肽、司美格鲁肽、度拉糖肽）的剂量可带来更好的血糖控制效果，而且可能会有更大程度的体重减轻。每日剂量为3.0毫克的利拉鲁肽和每周剂量为2.4毫克的司美格鲁肽已获批用于肥胖症治疗。最近的一项创新是开发了靶向GLP-1和GIP（“葡萄糖依赖性促胰岛素多肽”）受体的双分子激动剂（替尔泊肽）或靶向GLP-1和胰高血糖素受体的双分子激动剂（可他肽）。在SURPASS项目中，替尔泊肽使糖化血红蛋白水平和体重显著降低，降幅大于度拉糖肽或司美格鲁肽。替尔泊肽已获批用于治疗T2D，目前正在进行肥胖症治疗试验（SURMOUNT项目）。有趣的是，目前正在开发GIP/GLP-1/胰高血糖素三联激动剂用于T2D和肥胖症的管理，也有望用于治疗代谢相关脂肪性肝病。
