Imperial College Healthcare NHS Trust, London, UK.
School of Medicine, Ulster University, Derry~Londonderry, UK.
Intern Emerg Med. 2023 Jun;18(4):1019-1030. doi: 10.1007/s11739-023-03237-4. Epub 2023 May 30.
Substantial leaps have been made in the drug discovery front in tackling the growing pandemic of obesity and its metabolic co-morbidities. Greater mechanistic insight and understanding of the gut-brain molecular pathways at play have enabled the pursuit of novel therapeutic agents that possess increasingly efficacious weight-lowering potential whilst remaining safe and tolerable for clinical use. In the wake of glucagon-like peptide 1 (GLP-1) based therapy, we look at recent advances in gut hormone biology that have fermented the development of next generation pharmacotherapy in diabesity that harness synergistic potential. In this paper, we review the latest data from the SURPASS and SURMOUNT clinical trials for the novel 'twincretin', known as Tirzepatide, which has demonstrated sizeable body weight reduction as well as glycaemic efficacy. We also provide an overview of amylin-based combination strategies and other emerging therapies in the pipeline that are similarly providing great promise for the future of chronic management of obesity.
在应对肥胖症及其代谢合并症日益严重的问题上，药物发现领域取得了重大进展。对肠道-大脑分子途径的作用机制有了更深入的了解，这使得人们能够追求新型治疗药物，这些药物具有越来越有效的减肥潜力，同时保持安全和耐受临床使用。在基于胰高血糖素样肽 1 (GLP-1) 的治疗之后，我们着眼于肠道激素生物学的最新进展，这些进展促进了下一代治疗糖尿病肥胖症的药物的发展，利用了协同潜力。在本文中，我们回顾了新型“双激素”——Tirzepatide 的 SURPASS 和 SURMOUNT 临床试验的最新数据，该药物已证明具有显著的体重减轻和血糖疗效。我们还概述了基于胰淀素的联合策略和其他正在研发中的新兴疗法，这些疗法同样为肥胖症的慢性管理的未来提供了巨大的希望。
