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Several glucagon\u2010like peptide\u20101 receptor agonists (GLP\u20101RAs) and other agents are in various phases of clinical development for use in MASH; an ideal therapy should reduce liver fat content, improve chronic liver disease, help mitigate metabolic comorbidities and decrease all\u2010cause mortality. Because of interconnected disease mechanisms, metabolic dysfunction\u2010associated steatotic liver disease\/MASH often coexists with type 2 diabetes (T2D), obesity and cardiovascular disease. Various GLP\u20101RAs are Food and Drug Administration\u2010approved for use in T2D, and two, liraglutide and semaglutide, are approved for overweight and obesity. GLP\u20101RAs decrease glucose levels and body weight and improve cardiovascular outcomes in people with T2D who are at high risk of cardiovascular disease. In addition, GLP\u20101RAs have been reported to reduce liver fat content and liver enzymes, reduce oxidative stress and improve hepatic de novo lipogenesis and the histopathology of MASH. Weight loss may contribute to these effects; however, the exact mechanisms are unknown. Adverse events that are commonly associated with GLP\u20101RAs include vomiting, nausea and diarrhoea. There is a lack of evidence from meta\u2010analyses regarding the increased risk of acute pancreatitis and various forms of cancer with GLP\u20101RAs. Large\u2010scale, phase 3 trials, which will provide definitive data on GLP\u20101RAs and other potential therapies in MASH, are ongoing. Given the spectrum of modalities under investigation, it is hoped that these trials will support the identification of pharmacotherapies that provide clinical benefit for patients with MASH.<\/jats:p>","DOI":"10.1111\/dom.15524","type":"journal-article","created":{"date-parts":[[2024,3,21]],"date-time":"2024-03-21T05:34:31Z","timestamp":1710999271000},"page":"2001-2016","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":43,"title":["The role of glucagon\u2010like peptide\u20101 receptor agonists in metabolic dysfunction\u2010associated steatohepatitis"],"prefix":"10.1111","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5001-8618","authenticated-orcid":false,"given":"Manal F.","family":"Abdelmalek","sequence":"first","affiliation":[{"name":"Division of Gastroenterology and Hepatology Mayo Clinic  Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen A.","family":"Harrison","sequence":"additional","affiliation":[{"name":"Radcliffe Department of Medicine University of Oxford  Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arun J.","family":"Sanyal","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Hepatology and Nutrition Virginia Commonwealth University, School of Medicine  Richmond Virginia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,3,21]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.28431"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1097\/hep.0000000000000520"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.29466"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1053\/gast.2001.23256"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1053\/jhep.2002.30692"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0002\u20109343(99)00271\u20105"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v20.i27.9072"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep4.1689"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2020.2298"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1161\/atv.0000000000000153"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers13225844"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/dom.14322"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/oby.23263"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhepr.2019.07.002"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eprac.2022.03.010"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2022.06.023"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41575\u2010019\u20100144\u20108"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/dom.14569"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2023.07.033"},{"key":"e_1_2_10_21_1","unstructured":"US Food and Drug Administration.Highlights of prescribing information (exenatide for subcutaneous use).2020. 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