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We conducted a target trial emulation study to evaluate whether GLP-1RA decreases the risk of liver and non-liver outcomes.Methods: Patients with T2D and MASLD initiating GLP-1RA or dipeptidyl peptidase-4 inhibitor (DPP-4i) were included from 2013 to 2022 in Merative\u2122 Marketscan\u00ae Research Databases. Primary outcomes included incidences of (1) hepatocellular carcinoma (HCC) and cirrhosis, and (2) cardiovascular disease (CVD), chronic kidney disease (CKD), and non-liver cancer. Inverse probability of treatment weighting was applied to balance baseline characteristics and Cox regression models were conducted to estimate hazard ratio (HR) and 95% confidence interval (CI).Results: In the intention-to-treat design, GLP-1RA, compared with DPP-4i, had a significantly lower incidence (per 1,000 person-years) of HCC (0.8 vs. 1.7; HR 0.53, 95% CI 0.39\u20130.71), of cirrhosis (29.3 vs. 32.9; HR 0.91, 95% CI 0.86\u20130.96), of CVD (57.2 vs. 73.9; HR 0.90, 95% CI 0.86\u20130.95), of CKD (4.5 vs. 6.8; HR 0.73, 95% CI 0.64\u20130.84), and of non-liver cancer (16.9 vs. 22.9; HR 0.82, 95% CI 0.77\u20130.89). In the per-protocol design, significant inverse associations for these study outcomes still were observed, with HR 0.60\u20130.77.Conclusions: In this emulated target trial of nationwide patients with T2D and MASLD, GLP-1RA use, when compared with DPP-4i, was associated with a significantly lower risk of liver and non-liver complications.<\/jats:p>","DOI":"10.3350\/cmh.2024.1096","type":"journal-article","created":{"date-parts":[[2025,4,23]],"date-time":"2025-04-23T19:56:24Z","timestamp":1745438184000},"page":"1084-1099","update-policy":"https:\/\/doi.org\/10.3350\/crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Glucagon-like peptide 1 receptor agonist and reduced liver and non-liver complications in adults with type 2 diabetes and metabolic dysfunction-associated steatotic liver disease: a target trial emulation study"],"prefix":"10.3350","volume":"31","author":[{"given":"Xianhua","family":"Mao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinrong","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rongtao","family":"Lai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ka-Shing","family":"Cheung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Man-Fung","family":"Yuen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramsey","family":"Cheung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wai-Kay","family":"Seto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6275-4989","authenticated-orcid":true,"given":"Mindie H.","family":"Nguyen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1902","reference":[{"key":"ref1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2023.04.036"},{"key":"ref2","doi-asserted-by":"publisher","DOI":"10.1016\/s2468-1253(22)00165-0"},{"key":"ref3","volume-title":""},{"key":"ref4","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2020.12.033"},{"key":"ref5","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2020.12.022"},{"key":"ref6","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.34637"},{"key":"ref7","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2019.06.021"},{"key":"ref8","first-page":"S49","volume-title":"4. 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