Muzurović Emir, Haluzik Martin, Horváth Ludek, Vlacho Bogdan, Mauricio Didac
Department of Internal Medicine, Endocrinology Section, Clinical Centre of Montenegro, Podgorica, Montenegro.
Faculty of Medicine, University of Montenegro, Podgorica, Montenegro.
Curr Pharm Des. 2025 Jul 9. doi: 10.2174/0113816128378484250619080753.
Metabolic-dysfunction-associated steatotic liver disease (MASLD) is the most prevalent liver disease worldwide, primarily driven by the rising prevalence of both obesity and type 2 diabetes mellitus (T2DM). Historically, treatment options for patients with more advanced stages of hepatic dysfunction (steatohepatitis, fibrosis, cirrhosis) have been limited, with only resmetirom, a thyroid hormone receptor-β agonist, recently being approved for use as a metabolic dysfunction-associated steatohepatitis (MASH)-specific treatment option. Incretin-based receptor agonists are emerging as promising treatments for MASLD, and multiple liver-biopsy powered trials are underway. This group of drugs has gained attention as possible treatment options for MASLD/MASH, due to their significant weight-loss and body fat reduction effects, and there is also a growing body of evidence that incretin-based agents lead to a significant reduction in liver fat content. However, the evidence concerning improvement of steatohepatitis and/or fibrosis is limited. Most authorities consider incretin mimetics to be only one contributing factor to the treatment paradigm of the MASLD/MASH/ fibrosis/cirrhosis continuum. Specifically, according to the data to date, incretin-based treatments may improve metabolic abnormalities in MASLD/MASH patients, especially in patients with obesity and/or T2DM, and may mitigate its progression at the early stages. However, no incretin-based treatment is officially approved in this indication yet. This review discusses the rationale for the use of incretin-based treatment options in patients with MASLD/MASH, explaining the pathophysiological background of this disorder and describing the possible mechanism of action of these drugs.
代谢功能障碍相关脂肪性肝病（MASLD）是全球最常见的肝脏疾病，主要由肥胖症和2型糖尿病（T2DM）患病率的上升所驱动。从历史上看，对于肝功能障碍更晚期（脂肪性肝炎、纤维化、肝硬化）患者的治疗选择一直有限，最近只有甲状腺激素受体-β激动剂resmetirom被批准用作代谢功能障碍相关脂肪性肝炎（MASH）的特异性治疗选择。基于肠促胰素的受体激动剂正成为治疗MASLD的有前景的方法，多项基于肝活检的试验正在进行中。由于这类药物具有显著的减肥和减少体脂的作用，它们作为MASLD/MASH的可能治疗选择受到了关注，而且越来越多的证据表明基于肠促胰素的药物可使肝脏脂肪含量显著降低。然而，关于改善脂肪性肝炎和/或纤维化的证据有限。大多数权威人士认为，肠促胰素类似物只是MASLD/MASH/纤维化/肝硬化连续体治疗模式的一个促成因素。具体而言，根据迄今为止的数据，基于肠促胰素的治疗可能改善MASLD/MASH患者的代谢异常，尤其是肥胖和/或T2DM患者，并可能在疾病早期减轻其进展。然而，目前尚无基于肠促胰素的治疗在该适应症上获得官方批准。本综述讨论了在MASLD/MASH患者中使用基于肠促胰素的治疗选择的基本原理，解释了这种疾病的病理生理背景，并描述了这些药物可能的作用机制。
