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However, therapeutic options for MAFLD are currently limited. Glucolipid dysregulation drives MAFLD pathogenesis through intertwined glucose metabolic imbalance and lipid accumulation. Patients with type 2 diabetes mellitus (T2DM) are particularly prone to developing MASH and are at a higher risk of progressing to cirrhosis and hepatocellular carcinoma. The coexistence of MAFLD and T2DM correlates with clinical prognosis and elevates the risk of extrahepatic complications. Given the close association between MAFLD and T2DM, glucagon\u2010like peptide\u20101 receptor agonists (GLP\u20101RAs), which have been approved for the treatment of T2DM and obesity, were the first to be investigated in patients with MAFLD\/MASH. Recently, beyond GLP\u20101RAs, novel combination agents integrating glucose\u2010dependent insulinotropic peptide receptor (GIPR) and\/or glucagon receptor (GCR) agonists have also been explored. A large number of phase II randomized clinical trials have demonstrated significant improvements in body weight, insulin resistance, and liver parameters. Thus, GLP\u20101RAs and dual\/triple agonists are promising for MAFLD\/MASH, especially in those with obesity or T2DM. This study explores mechanisms and clinical evidence of incretin\u2010based therapies for MAFLD by targeting its core pathogenesis\u2014glucolipid disorders. With growing evidence, it also forecasts the broad clinical prospects on MAFLD treatment.<\/jats:p>","DOI":"10.1002\/cpt.70131","type":"journal-article","created":{"date-parts":[[2025,11,17]],"date-time":"2025-11-17T08:27:52Z","timestamp":1763368072000},"page":"336-349","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Advances in Incretin\u2010Based Therapies for MAFLD: Mechanisms and Clinical Evidence"],"prefix":"10.1002","volume":"119","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-3319-8089","authenticated-orcid":false,"given":"Wenqi","family":"Dong","sequence":"first","affiliation":[{"name":"Department of Gastroenterology Union Hospital, Tongji Medical College, Huazhong University of Science and Technology  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7669-5353","authenticated-orcid":false,"given":"Haiming","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Integrated Traditional Chinese and Western Medicine The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-7810-0690","authenticated-orcid":false,"given":"Shaowei","family":"Mu","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary Surgery Peking University People\u2019s Hospital  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-2265-0114","authenticated-orcid":false,"given":"Shuyi","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Union Hospital, Tongji Medical College, Huazhong University of Science and Technology  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2792-3094","authenticated-orcid":false,"given":"Junli","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Union Hospital, Tongji Medical College, Huazhong University of Science and Technology  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-4600-0034","authenticated-orcid":false,"given":"Keshu","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Union Hospital, Tongji Medical College, Huazhong University of Science and Technology  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,11,17]]},"reference":[{"key":"e_1_2_11_1_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2020.03.039"},{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2019.11.312"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12072-020-10094-2"},{"key":"e_1_2_11_4_1","first-page":"955","article-title":"Guideline for the prevention and treatment of metabolic dysfunction\u2010associated fatty liver disease (version 2024)","volume":"12","author":"Fan J.\u2010G.","year":"2024","journal-title":"J. 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