胰高血糖素和胰高血糖素受体激动剂在代谢功能障碍相关性脂肪肝中的作用:机遇与挑战。

IF 2.5 Q2 GASTROENTEROLOGY & HEPATOLOGY
Chencheng Xie, Naim Alkhouri, Mohamed A Elfeki
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引用次数: 0

摘要

代谢功能障碍相关性脂肪性肝病(MASLD)已成为全球最常见的慢性肝病,与此同时,肥胖症和 2 型糖尿病的发病率也在不断上升。由于代谢相关性脂肪性肝病对全球健康造成的负担日益加重,且发病机制复杂,因此需要一种多方面的创新治疗方法。最初开发用于糖尿病治疗的内分泌受体激动剂已成为治疗 MASLD 的有前途的候选药物。本综述介绍了三大类增量素/胰高血糖素受体激动剂的病理生理机制和作用部位: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。胰岛素和胰高血糖素直接或间接影响多个器官,包括肝脏、大脑、胰腺、胃肠道和脂肪组织。因此,这些药物能明显改善血糖控制和体重管理,减轻 MASLD 的发病机制。重要的是,本研究总结了分析增量素受体激动剂在MASLD治疗中的有效性和安全性的临床试验,并深入分析了这些药物对改善肝功能、肝脂肪变性和肝内炎症的有益作用。本综述详细讨论了在现实世界中使用这些药物所面临的新挑战,特别是不良事件、药物间相互作用和使用障碍。此外,本综述还强调了增量素受体激动剂在 MASLD 治疗中不断演变的作用,并提出了未来的研究方向。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Role of incretins and glucagon receptor agonists in metabolic dysfunction-associated steatotic liver disease: Opportunities and challenges.

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.

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来源期刊
World Journal of Hepatology
World Journal of Hepatology GASTROENTEROLOGY & HEPATOLOGY-
CiteScore
4.10
自引率
4.20%
发文量
172
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