{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:46:51Z","timestamp":1792788411244,"version":"4.5.0"},"reference-count":25,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2019,11,29]],"date-time":"2019-11-29T00:00:00Z","timestamp":1574985600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2019,11,29]],"date-time":"2019-11-29T00:00:00Z","timestamp":1574985600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Drug Effectiveness Review Project","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Syst Rev"],"published-print":{"date-parts":[[2019,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Fatty liver is associated with obesity, type 2 diabetes, hyperlipidemia, hypertension, and metabolic syndrome. While there are no approved drugs for the treatment of nonalcoholic fatty liver disease (NAFLD) or nonalcoholic steatohepatitis, strategies to ameliorate fatty liver often target these related diseases. We sought to determine if any medications approved by the US Food and Drug Administration to treat diabetes are helpful in reducing weight and improving steatohepatitis in patients with NAFLD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We conducted a systematic review of published and unpublished studies evaluating the comparative effectiveness and harms of diabetes medications for the treatment of NAFLD. We searched MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, and the Cochrane Central Register of Controlled Trials through 3rd quarter, 2019 using terms for included drugs and indications.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We screened 1591 citations and included 18 trials of diabetes drugs to treat NAFLD. Studies of metformin found no difference from placebo in steatosis, fibrosis, NAFLD activity score, or resolution of NASH. While weight and glucose control were improved with metformin, it did not substantially impact liver disease. Studies of pioglitazone in NASH patients found benefits in liver function, liver fat, and NASH resolution, though significant increases in weight may be cause for concern. Evidence for other thiazolinediones was more limited and had somewhat mixed results, but findings were generally consistent with those for pioglitazone: liver fat and function and glucose measures improved, but weight also increased. We found some evidence that liraglutide improves liver fat, liver function, and HbA1c and is effective at resolving NASH and reducing weight. Exenatide performed less well but also resulted in significant reductions in liver fat and weight.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Consistent with existing clinical practice guidelines, which recommend lifestyle intervention and treatment for comorbidities related to fatty liver disease as first-line treatment, trial evidence supports the efficacy of some diabetes drugs (especially pioglitazone) in patients with NAFLD or NASH, though weight gain with some diabetes drugs may warrant caution. Larger trials are needed to better characterize the efficacy and harms of diabetes pharmacotherapy in these patients.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13643-019-1200-8","type":"journal-article","created":{"date-parts":[[2019,11,29]],"date-time":"2019-11-29T10:03:04Z","timestamp":1575021784000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":65,"title":["Diabetes drugs for nonalcoholic fatty liver disease: a systematic review"],"prefix":"10.1186","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0164-6674","authenticated-orcid":false,"given":"Ian","family":"Blazina","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shelley","family":"Selph","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,11,29]]},"reference":[{"key":"1200_CR1","unstructured":"National Guideline C. National Institute for Health and Care Excellence: Guidance. Non-alcoholic fatty liver disease: assessment and management. London: National Institute for Health and Care Excellence (UK) Copyright (c) National Institute for Health and Care Excellence 2016.; 2016."},{"issue":"1","key":"1200_CR2","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1002\/hep.28431","volume":"64","author":"ZM Younossi","year":"2016","unstructured":"Younossi ZM, Koenig AB, Abdelatif D, Fazel Y, Henry L, Wymer M. Global epidemiology of nonalcoholic fatty liver disease-meta-analytic assessment of prevalence, incidence, and outcomes. Hepatology. 2016;64(1):73\u201384.","journal-title":"Hepatology."},{"issue":"6","key":"1200_CR3","doi-asserted-by":"publisher","first-page":"1245","DOI":"10.1016\/j.jhep.2016.07.033","volume":"65","author":"R Pais","year":"2016","unstructured":"Pais R, Barritt AS, Calmus Y, Scatton O, Runge T, Lebray P, et al. NAFLD and liver transplantation: current burden and expected challenges. Journal of hepatology. 2016;65(6):1245\u201357.","journal-title":"Journal of hepatology."},{"issue":"5","key":"1200_CR4","doi-asserted-by":"publisher","first-page":"535","DOI":"10.1080\/17512433.2017.1300059","volume":"10","author":"S Cernea","year":"2017","unstructured":"Cernea S, Cahn A, Raz I. Pharmacological management of nonalcoholic fatty liver disease in type 2 diabetes. Expert review of clinical pharmacology. 2017;10(5):535\u201347.","journal-title":"Expert review of clinical pharmacology."},{"key":"1200_CR5","doi-asserted-by":"publisher","first-page":"140","DOI":"10.1186\/1471-2288-12-140","volume":"12","author":"MS McDonagh","year":"2012","unstructured":"McDonagh MS, Jonas DE, Gartlehner G, Little A, Peterson K, Carson S, et al. Methods for the drug effectiveness review project. 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Liraglutide safety and efficacy in patients with non-alcoholic steatohepatitis (LEAN): a multicentre, double-blind, randomised, placebo-controlled phase 2 study. Lancet. 2016;387(10019):679\u201390.","journal-title":"Lancet."},{"issue":"8","key":"1200_CR10","first-page":"OC19","volume":"10","author":"H Rana","year":"2016","unstructured":"Rana H, Yadav SS, Reddy HD, Singhal S, Singh DK, Usman K. Comparative effect of insulin sensitizers and statin on metabolic profile and ultrasonographical score in non alcoholic fatty liver disease. Journal of Clinical and Diagnostic Research. 2016;10(8):OC19\u201323.","journal-title":"Journal of Clinical and Diagnostic Research."},{"issue":"4","key":"1200_CR11","doi-asserted-by":"publisher","first-page":"333","DOI":"10.1016\/j.jceh.2012.10.010","volume":"2","author":"BC Sharma","year":"2012","unstructured":"Sharma BC, Kumar A, Garg V, Reddy RS, Sakhuja P, Sarin SK. 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