Farrugia Marwin A, Pini Enzo, Tran Albert, Chevalier Nicolas, Anty Rodolphe, Gual Philippe
Université Côte d'Azur, CHU, INSERM, U1065, C3M, Nice, France.
Université Côte d'Azur, INSERM, U1065, C3M, Nice, France.
Curr Obes Rep. 2025 Jun 25;14(1):56. doi: 10.1007/s13679-025-00646-8.
The aim of this paper is to provide an overview of metabolic dysfunction-associated steatotic liver disease (MASLD) pathogenesis, focusing on how incretin analogues might affect liver function and disease. It also summarizes the latest preclinical studies and clinical trials evaluating the impact of incretin analogues (single or multi-agonists) on metabolic dysfunction-associated steatohepatitis (MASH) and liver fibrosis.
Incretin analogues have recently been added to the therapeutic arsenal of diabetologists, and their therapeutic effects on insulin resistance and T2DM are now well established. These treatments have also demonstrated beneficial effects on cardiovascular complications. In addition, the weight loss associated with these molecules has recently extended their indication to the treatment of obesity. On the other hand, pharmacological treatments for MASLD are still very limited, and mainly target liver functions. As weight loss is the cornerstone of MASLD treatment, studies evaluating these analogues and combinations with other compounds are very promising. Incretin analogues appear to be effective treatments for MASH and fibrosis in a large number of clinical trials. Phase 3 studies are currently ongoing to confirm these results. Further treatments may emerge, such as double and triple receptor agonists. A multidisciplinary approach, involving diabetologists and hepatologists, is optimal for the management of MASLD.
本文旨在概述代谢功能障碍相关脂肪性肝病（MASLD）的发病机制，重点关注肠促胰岛素类似物如何影响肝功能和疾病。本文还总结了评估肠促胰岛素类似物（单激动剂或多激动剂）对代谢功能障碍相关脂肪性肝炎（MASH）和肝纤维化影响的最新临床前研究和临床试验。
肠促胰岛素类似物最近已被纳入糖尿病专家的治疗手段，其对胰岛素抵抗和2型糖尿病的治疗效果现已得到充分证实。这些治疗方法对心血管并发症也显示出有益效果。此外，与这些分子相关的体重减轻最近将其适应证扩展到了肥胖症的治疗。另一方面，MASLD的药物治疗仍然非常有限，主要针对肝功能。由于体重减轻是MASLD治疗的基石，评估这些类似物以及与其他化合物联合使用的研究非常有前景。在大量临床试验中，肠促胰岛素类似物似乎是治疗MASH和纤维化的有效方法。目前正在进行3期研究以证实这些结果。可能会出现进一步的治疗方法，如双受体和三受体激动剂。对于MASLD的管理，采用糖尿病专家和肝病专家参与的多学科方法最为理想。
