{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T05:37:14Z","timestamp":1769751434553,"version":"3.49.0"},"reference-count":20,"publisher":"Georg Thieme Verlag KG","issue":"04","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Drug Res (Stuttg)"],"published-print":{"date-parts":[[2023,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>\n          Background This study aimed to evaluate the effectiveness of metformin and\n                    pioglitazone in combination with vitamin E on sonography grade and liver enzymes\n                    level in patients with non-alcoholic fatty liver disease.<\/jats:p><jats:p>\n          Methods A randomized controlled clinical trial was designed with 68\n                    patients diagnosed with non-alcoholic fatty liver disease by sonography and\n                    clinical examinations. Sixty-eight patients were randomly divided into two\n                    groups; 34 were assigned to receive 15\u2009mg of pioglitazone per day and 34\n                    were assigned to receive 1000\u2009mg of metformin per day for 6 months. All\n                    of the patients received vitamin E at a dose of 800 IU daily for six months. The\n                    sonography grade of fatty liver and the levels of alanine aminotransferase and\n                    aspartate aminotransferase of patients were evaluated at baseline, and within\n                    three and six months after initiation of the intervention.<\/jats:p><jats:p>\n          Results The use of metformin or pioglitazone in combination with vitamin E\n                    decreased the sonography grade of non-alcoholic fatty liver disease patients\n                    after 6 months of treatment (p-value&lt;0.05); however, patients in\n                    metformin group benefit more compared to pioglitazone group. Patients who\n                    received metformin and vitamin E had a significant reduction in the levels of\n                    alanine aminotransferase and aspartate aminotransferase (p-value&lt;0.05).\n                    There were no significant changes in the liver enzymes level of the patients who\n                    received pioglitazone and vitamin E (p-value&gt;0.05).<\/jats:p><jats:p>\n          Major conclusion The concomitant use of metformin and vitamin E\n                    significantly improves the sonography grade of fatty liver and the level of\n                    liver enzymes in patients with non-alcoholic fatty liver disease.<\/jats:p>","DOI":"10.1055\/a-1997-0401","type":"journal-article","created":{"date-parts":[[2023,2,16]],"date-time":"2023-02-16T00:03:38Z","timestamp":1676505818000},"page":"232-237","source":"Crossref","is-referenced-by-count":5,"title":["Comparison of the efficacy of pioglitazone and metformin on\n                    ultrasound grade and liver enzymes level in patients with non-alcoholic fatty\n                    liver disease: A randomized controlled clinical trial"],"prefix":"10.1055","volume":"73","author":[{"given":"Manouchehr","family":"Khoshbaten","sequence":"additional","affiliation":[{"name":"Liver and Gastrointestinal Diseases Research Center, Tabriz University\n                    of Medical Sciences, Tabriz, Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Samineh","family":"Beheshtirouy","sequence":"additional","affiliation":[{"name":"Department of clinical pharmacy, Faculty of pharmacy, Tabriz University\n                    of Medical, Sciences, Tabriz, Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shahrzad","family":"Shayanrad","sequence":"additional","affiliation":[{"name":"Student Research Committee, Faculty of Pharmacy, Tabriz University of\n                    Medical Sciences, Tabriz, Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Afshin","family":"Gharekhani","sequence":"additional","affiliation":[{"name":"Department of clinical pharmacy, Faculty of pharmacy, Tabriz University\n                    of Medical, Sciences, Tabriz, Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haleh","family":"Rezaee","sequence":"additional","affiliation":[{"name":"Department of clinical pharmacy, Faculty of pharmacy, Tabriz University\n                    of Medical, Sciences, Tabriz, Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"194","published-online":{"date-parts":[[2023,2,15]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1080\/03602532.2017.1293683","article-title":"Non-alcoholic fatty liver disease (NAFLD)\u2013pathogenesis, classification,\n                    and effect on drug metabolizing enzymes and transporters","volume":"49","author":"E Cobbina","year":"2017","journal-title":"Drug metabolism reviews"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"1017","DOI":"10.1016\/j.metabol.2016.01.012","article-title":"Epidemiology and natural history of non-alcoholic fatty liver disease","volume":"65","author":"Y Fazel","year":"2016","journal-title":"Metabolism"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1055\/s-0035-1562942","article-title":"Diagnosis and Assessment of NAFLD: Definitions and Histopathological\n                    Classification","volume":"35","author":"A D Burt","year":"2015","journal-title":"Semin Liver Dis"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"1038","DOI":"10.1016\/j.metabol.2015.12.012","article-title":"The multiple-hit pathogenesis of non-alcoholic fatty liver disease (NAFLD","volume":"65","author":"E Buzzetti","year":"2016","journal-title":"Metabolism"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.metabol.2017.02.014","article-title":"The use of statins alone, or in combination with pioglitazone and other drugs,\n                    for the treatment of non-alcoholic fatty liver disease\/non-alcoholic\n                    steatohepatitis and related cardiovascular risk. An Expert Panel Statement","volume":"71","author":"V G Athyros","year":"2017","journal-title":"Metabolism"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"367","DOI":"10.4172\/2472-1891.100014","article-title":"Pathology of non-alcoholic fatty liver disease","volume":"2","author":"L Wang","year":"2016","journal-title":"Int J Dig Dis"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1136\/gutjnl-2016-312431","article-title":"Current and upcoming pharmacotherapy for non-alcoholic fatty liver disease","volume":"66","author":"Y Rotman","year":"2017","journal-title":"Gut"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"1773","DOI":"10.1007\/s10620-012-2118-3","article-title":"Lipid-lowering agents in nonalcoholic fatty liver disease and steatohepatitis:\n                    human studies","volume":"57","author":"W Nseir","year":"2012","journal-title":"Dig Dis Sci"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"1179552218787502","DOI":"10.1177\/1179552218787502","article-title":"An Evidence-Based Review of Statin Use in Patients With Nonalcoholic Fatty Liver\n                    Disease","volume":"11","author":"M A Sigler","year":"2018","journal-title":"Clin Med Insights Gastroenterol"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"253","DOI":"10.1042\/CS20110386","article-title":"Cellular and molecular mechanisms of metformin: an overview","volume":"122","author":"B Viollet","year":"2012","journal-title":"Clin Sci (Lond)"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"e6099","DOI":"10.5812\/hepatmon.6099","article-title":"Effects of metformin, pioglitazone, and silymarin treatment on non-alcoholic\n                    Fatty liver disease: a randomized controlled pilot study","volume":"12","author":"A A Hajiaghamohammadi","year":"2012","journal-title":"Hepat Mon"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"703","DOI":"10.1093\/ajcn\/76.4.703","article-title":"The European perspective on vitamin E: current knowledge and future\n                    research","volume":"76","author":"R Brigelius-Floh\u00e9","year":"2002","journal-title":"The American Journal of Clinical Nutrition"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"3361","DOI":"10.3748\/wjg.v24.i30.3361","article-title":"Current guidelines for the management of non-alcoholic fatty liver disease: A\n                    systematic review with comparative analysis","volume":"24","author":"S Leoni","year":"2018","journal-title":"World J Gastroenterol"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1007\/s11695-013-1044-6","article-title":"Does a Calculated \u201cNAFLD Fibrosis Score\u201d Reliably Negate the\n                    Need for Liver Biopsy in Patients Undergoing Bariatric Surgery?","volume":"24","author":"K A Simo","year":"2014","journal-title":"Obesity Surgery"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"172","DOI":"10.1111\/j.1365-2036.2008.03869.x","article-title":"Clinical trial: pilot study of metformin for the treatment of non-alcoholic\n                    steatohepatitis","volume":"29","author":"R Loomba","year":"2009","journal-title":"Aliment Pharmacol Ther"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"1082","DOI":"10.1111\/j.1572-0241.2005.41583.x","article-title":"A randomized controlled trial of metformin versus vitamin E or prescriptive diet\n                    in nonalcoholic fatty liver disease","volume":"100","author":"E Bugianesi","year":"2005","journal-title":"Am J Gastroenterol"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"57","DOI":"10.3892\/br.2012.18","article-title":"Metformin in non-alcoholic fatty liver disease: A systematic review and\n                    meta-analysis","volume":"1","author":"Y Li","year":"2013","journal-title":"Biomed Rep"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"1659","DOI":"10.1001\/jama.2011.520","article-title":"Effect of vitamin E or metformin for treatment of nonalcoholic fatty liver\n                    disease in children and adolescents: the TONIC randomized controlled trial","volume":"305","author":"J E Lavine","year":"2011","journal-title":"Jama"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"1180","DOI":"10.1001\/jama.298.10.1180","article-title":"Pioglitazone and risk of cardiovascular events in patients with type 2 diabetes\n                    mellitus: a meta-analysis of randomized trials","volume":"298","author":"A M Lincoff","year":"2007","journal-title":"Jama"},{"key":"ref20","doi-asserted-by":"publisher","first-page":"1675","DOI":"10.1056\/NEJMoa0907929","article-title":"Pioglitazone, vitamin E, or placebo for nonalcoholic steatohepatitis","volume":"362","author":"A J Sanyal","year":"2010","journal-title":"N Engl J Med"}],"container-title":["Drug 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