Alkhouri Naim, Charlton Michael, Gray Meagan, Noureddin Mazen
Department of Hepatology, Arizona Liver Health, Phoenix, AZ, USA.
Transplant Institute, Center for Liver Diseases, University of Chicago Biological Sciences, Chicago, IL, USA.
Expert Opin Investig Drugs. 2025 Mar;34(3):169-195. doi: 10.1080/13543784.2025.2473062. Epub 2025 Mar 17.
INTRODUCTION: Glucagon-like peptide-1 receptor agonists (GLP-1RAs), and dual GLP-1/glucose-dependent insulinotropic peptide (GIP) or glucagon receptor agonists have emerged as promising agents to treat metabolic dysfunction-associated steatotic liver disease (MASLD)/metabolic dysfunction-associated steatohepatitis (MASH). Although the beneficial effects of GLP-1RAs on glycemic control and weight are well-established, clinicians may be unfamiliar with other potential benefits of this class. AREAS COVERED: We examined the pleiotropic effects of GLP-1RAs and how they relate to gastroenterologists for MASLD/MASH treatment. Our narrative review of English articles included four GLP-1RAs (subcutaneous semaglutide, liraglutide, dulaglutide, and efpeglenatide), a dual GLP-1/GIP agonist (tirzepatide), a dual GLP-1/glucagon receptor agonist (survodutide), MASLD/MASH, related disorders, clinical management, treatment outcomes and landscape. EXPERT OPINION: In Phase I - III trials, GLP-1RAs are associated with clinically relevant hepatic improvements including MASH resolution, liver fat reduction, and preventing worsening fibrosis. Effects on cardiometabolic parameters align with type 2 diabetes/obesity Phase III data, comprising substantial improvements in glycemic, weight, and cardiovascular outcomes. Promising data also suggest benefits in common comorbidities, including obstructive sleep apnea, polycystic ovary syndrome, chronic kidney disease, and heart failure with preserved ejection fraction.GLP-1RAs represent a valuable pharmacotherapeutic option for gastroenterologists managing individuals with MASLD/MASH and cardiometabolic comorbid conditions.
引言:胰高血糖素样肽-1受体激动剂(GLP-1RAs)以及双重GLP-1/葡萄糖依赖性促胰岛素多肽(GIP)或胰高血糖素受体激动剂已成为治疗代谢功能障碍相关脂肪性肝病(MASLD)/代谢功能障碍相关脂肪性肝炎(MASH)的有前景的药物。尽管GLP-1RAs对血糖控制和体重的有益作用已得到充分证实,但临床医生可能并不熟悉这类药物的其他潜在益处。 涵盖领域:我们研究了GLP-1RAs的多效性作用以及它们在MASLD/MASH治疗中与胃肠病学家的关联。我们对英文文章的叙述性综述包括四种GLP-1RAs(皮下注射司美格鲁肽、利拉鲁肽、度拉鲁肽和依弗那肽)、一种双重GLP-1/GIP激动剂(替尔泊肽)、一种双重GLP-1/胰高血糖素受体激动剂(苏沃鲁肽)、MASLD/MASH、相关疾病、临床管理、治疗结果及现状。 专家观点:在I - III期试验中,GLP-1RAs与临床上相关的肝脏改善有关,包括MASH的缓解、肝脏脂肪减少以及预防纤维化恶化。对心脏代谢参数的影响与2型糖尿病/肥胖症的III期数据一致,包括血糖、体重和心血管结局的显著改善。有前景的数据还表明,GLP-1RAs在常见合并症中也有益处,包括阻塞性睡眠呼吸暂停、多囊卵巢综合征、慢性肾脏病以及射血分数保留的心力衰竭。对于管理患有MASLD/MASH及心脏代谢合并症的个体的胃肠病学家而言,GLP-1RAs是一种有价值的药物治疗选择。
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