Grandl Gerald, Novikoff Aaron, Liu Xue, Müller Timo D
Institute for Diabetes and Obesity, Helmholtz Munich, Neuherberg, Germany.
German Center for Diabetes Research (DZD), Neuherberg, Germany.
Lancet Reg Health Eur. 2024 Nov 9;47:101100. doi: 10.1016/j.lanepe.2024.101100. eCollection 2024 Dec.
Pharmacological management of obesity long suffered from a reputation of a 'Mission Impossible,' with inefficient weight loss and/or unacceptable tolerability. However, the tide has turned with recent progress in biochemical engineering and the development of long-acting agonists at the receptor for glucagon-like peptide-1 (GLP-1), and with unimolecular peptides that simultaneously possess activity at the receptors for GLP-1, the glucose-dependent insulinotropic polypeptide (GIP) and glucagon. Some of these novel therapeutics not only improve body weight and glycemic control in individuals with obesity and type 2 diabetes with hitherto unmet efficacy and tolerable safety, but also exhibit potential therapeutic value in diverse areas such as neurodegenerative diseases, fatty liver disease, dyslipidemia, atherosclerosis, and cardiovascular diseases. In this review, we highlight recent advances in incretin-based therapies and discuss their pharmacological potential within and beyond the treatment of obesity and diabetes, as well as their limitations in use, side effects, and underlying molecular mechanisms.
肥胖症的药物治疗长期以来一直背负着“不可能完成的任务”之名，减肥效果不佳且/或耐受性不可接受。然而，随着生物化学工程的最新进展以及胰高血糖素样肽-1（GLP-1）受体长效激动剂的开发，以及同时在GLP-1、葡萄糖依赖性促胰岛素多肽（GIP）和胰高血糖素受体上具有活性的单分子肽的出现，情况已经发生了转变。其中一些新型疗法不仅能改善肥胖症和2型糖尿病患者的体重和血糖控制，疗效前所未有的好且安全性可耐受，还在神经退行性疾病、脂肪性肝病、血脂异常、动脉粥样硬化和心血管疾病等不同领域展现出潜在的治疗价值。在这篇综述中，我们重点介绍基于肠促胰岛素疗法的最新进展，并讨论其在肥胖症和糖尿病治疗内外的药理学潜力，以及其使用局限性、副作用和潜在分子机制。
