肥胖药物治疗的未来方向：新靶点与在研疗法。
完整摘要 · 中文译文
肥胖药物治疗可对抗机体对减重的适应性机制，这些机制会导致饥饿感和食物渴望增加、饱腹感降低以及能量消耗减少。第二代肥胖药物治疗包括基于营养刺激激素（NuSH）的疗法。具体而言，胰高血糖素样肽-1受体激动剂（GLP-1 RA）已显示出显著且持久的减重效果，包括FDA批准的司美格鲁肽和利拉鲁肽。替尔泊肽是一种GLP-1和葡萄糖依赖性促胰岛素多肽（GIP）双受体激动剂，已显示出更显著的减重和代谢获益。肥胖药物治疗的未来方向包括更多靶向胰高血糖素受体的共激动剂疗法，以及靶向GLP、GIP和胰高血糖素受体的三重激动剂，如瑞他鲁肽。基于胰淀素的药物可补充GLP-1 RA的作用，如卡格列肽-司美格鲁肽所展示的那样。此外，具有更高生物利用度的口服药物即将问世，如orforglipron，以及可能有助于保留肌肉量的药物如比马鲁单抗。基于NuSH的每月给药疗法如MariTide也正在研究中。本章探讨肥胖药物治疗的未来方向，包括新靶点以及处于2期和3期研发阶段的管线疗法。
完整摘要 · 英文原文
Obesity medications counteract the body's adaptive mechanisms to weight loss, which result in increased hunger and food cravings, reduced satiety, and decreased energy expenditure. Second generation obesity pharmacotherapy includes nutrient-stimulated hormone (NuSH)-based therapies. Specifically, GLP-1 RA have demonstrated significant and persistent weight loss and include the FDA approved therapies semaglutide and liraglutide. Tirzepatide is a dual GLP-1 and GIP RA that has demonstrated even more weight loss and metabolic benefits. Future directions in obesity pharmacotherapy include more co-agonist therapies targeting glucagon receptors as well as triple agonists targeting GLP, GIP and glucagon receptors like retatrutide. Amylin-based agents complement GLP-1 RA as demonstrated by cagrilinitide-semaglutide. Additionally, oral agents with increased bioavailability are on the horizon like orforglipron along with agents that may help preserve muscle mass like bimagrumab. NuSH-based therapies with monthly dosing like MariTide are also being researched. This chapter explores the future directions in obesity pharmacotherapy including the novel targets and pipeline therapies in phase 2 and phase 3 development.