Xie Chencheng, Alkhouri Naim, Elfeki Mohamed A
Department of Internal Medicine, University of South Dakota Sanford School of Medicine, Sioux Falls, SD 57105, United States.
Department of Hepatology, Avera Mckennan University Hospital and Transplant Institute, Sioux Falls, SD 57105, United States.
World J Hepatol. 2024 May 27;16(5):731-750. doi: 10.4254/wjh.v16.i5.731.
Metabolic dysfunction-associated steatotic liver disease (MASLD) has become the most common chronic liver disease worldwide, paralleling the rising pandemic of obesity and type 2 diabetes. Due to the growing global health burden and complex pathogenesis of MASLD, a multifaceted and innovative therapeutic approach is needed. Incretin receptor agonists, which were initially developed for diabetes management, have emerged as promising candidates for MASLD treatment. This review describes the pathophysiological mechanisms and action sites of three major classes of incretin/glucagon receptor agonists: glucagon-like peptide-1 receptor agonists, glucose-dependent insulinotropic polypeptide receptor agonists, and glucagon receptor agonists. Incretins and glucagon directly or indirectly impact various organs, including the liver, brain, pancreas, gastrointestinal tract, and adipose tissue. Thus, these agents significantly improve glycemic control and weight management and mitigate MASLD pathogenesis. Importantly, this study provides a summary of clinical trials analyzing the effectiveness and safety of incretin receptor agonists in MASLD management and provides an in-depth analysis highlighting their beneficial effects on improving liver function, hepatic steatosis, and intrahepatic inflammation. There are emerging challenges associated with the use of these medications in the real world, particularly adverse events, drug-drug interactions, and barriers to access, which are discussed in detail. Additionally, this review highlights the evolving role of incretin receptor agonists in MASLD management and suggests future research directions.
代谢功能障碍相关脂肪性肝病（MASLD）已成为全球最常见的慢性肝病，这与肥胖症和2型糖尿病的全球流行趋势同步上升。由于MASLD日益增加的全球健康负担和复杂的发病机制，需要一种多方面的创新治疗方法。最初为糖尿病管理而开发的肠促胰岛素受体激动剂已成为MASLD治疗的有希望的候选药物。本综述描述了三类主要的肠促胰岛素/胰高血糖素受体激动剂的病理生理机制和作用位点：胰高血糖素样肽-1受体激动剂、葡萄糖依赖性促胰岛素多肽受体激动剂和胰高血糖素受体激动剂。肠促胰岛素和胰高血糖素直接或间接影响包括肝脏、大脑、胰腺、胃肠道和脂肪组织在内的各种器官。因此，这些药物显著改善血糖控制和体重管理，并减轻MASLD的发病机制。重要的是，本研究总结了分析肠促胰岛素受体激动剂在MASLD管理中的有效性和安全性的临床试验，并提供了深入分析，突出了它们对改善肝功能、肝脂肪变性和肝内炎症的有益作用。在现实世界中使用这些药物存在一些新出现的挑战，特别是不良事件、药物相互作用和获取障碍，本文将详细讨论。此外，本综述强调了肠促胰岛素受体激动剂在MASLD管理中不断演变的作用，并提出了未来的研究方向。
