Clinical Research, Copenhagen University Hospital - Steno Diabetes Center Copenhagen, Herlev, Denmark.
Center for Clinical Metabolic Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark.
Diabetologia. 2023 Oct;66(10):1846-1858. doi: 10.1007/s00125-023-05966-9. Epub 2023 Jul 27.
In the last few decades, glucagon-like peptide-1 receptor (GLP-1R) agonists have changed current guidelines and improved outcomes for individuals with type 2 diabetes. However, the dual glucose-dependent insulinotropic polypeptide receptor (GIPR)/GLP-1R agonist, tirzepatide, has demonstrated superior efficacy regarding improvements in HbA and body weight in people with type 2 diabetes. This has led to increasing scientific interest in incretin hormones and incretin interactions, and several compounds based on dual- and multi-agonists are now being investigated for the treatment of metabolic diseases. Herein, we highlight the key scientific advances in utilising incretins for the treatment of obesity and, potentially, non-alcoholic fatty liver disease (NAFLD). The development of multi-agonists with multi-organ targets may alter the natural history of these diseases.
在过去的几十年中，胰高血糖素样肽-1 受体（GLP-1R）激动剂改变了当前的指南，并改善了 2 型糖尿病患者的预后。然而，双重葡萄糖依赖性胰岛素促分泌多肽受体（GIPR）/GLP-1R 激动剂替西帕肽在改善 2 型糖尿病患者的 HbA 和体重方面显示出更好的疗效。这导致人们对肠降血糖素激素和肠降血糖素相互作用越来越感兴趣，目前正在研究几种基于双重和多重激动剂的化合物来治疗代谢性疾病。在此，我们重点介绍了利用肠降血糖素治疗肥胖症的关键科学进展，并有可能治疗非酒精性脂肪性肝病（NAFLD）。具有多器官靶点的多重激动剂的开发可能会改变这些疾病的自然病程。
