Clinically effective pharmacological treatment(s) for metabolic dysfunction-associated steatotic liver disease (MASLD) and its progressive form metabolic dysfunction-associated steatohepatitis (MASH) represent a largely unmet need in medicine. Since glucagon-like peptide-1 receptor agonists (GLP-1RAs) have been licensed for the treatment of type 2 diabetes mellitus and obesity, they were one of the first drug classes to be examined in individuals with MASLD/MASH. Successful phase 2 randomised clinical trials with these agents have resulted in progression to phase 3 clinical trials (principally testing the long-term efficacy of subcutaneous semaglutide). Over the last few years, in addition to GLP-1RAs, newer agents with glucose-dependent insulinotropic peptide and/or glucagon receptor agonist functions have been tested, with increasing evidence from phase 2 randomised clinical trials of histological improvements in MASLD/MASH, as well as benefits on MASLD-related extrahepatic complications. Based on this background of evidence, single, dual or triple incretin receptor agonists are becoming an attractive and promising treatment option for MASLD or MASH, particularly in individuals with coexisting obesity or type 2 diabetes mellitus. In this narrative review, we examine the rapidly expanding body of clinical evidence supporting a role of incretin-based pharmacotherapies in delaying or reversing MASH progression. We also discuss the biology of incretins and the putative hepatoprotective mechanisms of incretin-based pharmacotherapies for managing MASLD or MASH.

中文翻译：

---

基于肠促胰岛素的 MASLD 治疗的最新进展：从单抗胰胰岛素受体激动剂到双抗或三抗肠促胰岛素受体激动剂


代谢功能障碍相关脂肪性肝病 （MASLD） 及其进展形式的代谢功能障碍相关脂肪性肝炎 （MASH） 的临床有效药物治疗代表了医学上基本未满足的需求。由于胰高血糖素样肽-1 受体激动剂 （GLP-1RAs） 已被批准用于治疗 2 型糖尿病和肥胖症，因此它们是首批在 MASLD/MASH 患者中进行检查的药物类别之一。使用这些药物的成功 2 期随机临床试验已进展到 3 期临床试验（主要测试皮下注射 semaglutide 的长期疗效）。在过去的几年里，除了 GLP-1RA 之外，还测试了具有葡萄糖依赖性促胰岛素肽和/或胰高血糖素受体激动剂功能的新型药物，来自 2 期随机临床试验的更多证据表明 MASLD/MASH 的组织学改善，以及对 MASLD 相关肝外并发症的益处。基于这一证据背景，单、双或三抗促胰岛素受体激动剂正在成为 MASLD 或 MASH 的有吸引力且有前途的治疗选择，尤其是在共存肥胖或 2 型糖尿病的个体中。在这篇叙述性综述中，我们研究了迅速扩展的临床证据，这些证据支持基于肠促胰岛素的药物治疗在延缓或逆转 MASH 进展中的作用。我们还讨论了肠促胰岛素的生物学和基于肠促胰岛素的药物治疗治疗 MASLD 或 MASH 的假定保肝机制。