{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T08:47:37Z","timestamp":1790412457376,"version":"4.1.0"},"reference-count":39,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2012,11,19]],"date-time":"2012-11-19T00:00:00Z","timestamp":1353283200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Aliment Pharmacol Ther"],"published-print":{"date-parts":[[2013,1]]},"abstract":"<jats:title>Summary<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Non\u2010alcoholic fatty liver disease has reached epidemic proportions in type 2 diabetes (T2D). Glucagon\u2010like peptide\u20101 analogues are licensed in T2D, yet little data exist on efficacy and safety in liver injury.<\/jats:p><\/jats:sec><jats:sec><jats:title>Aim<\/jats:title><jats:p>To assess the safety and efficacy of 26\u2010week liraglutide on liver parameters in comparison with active\u2010placebo.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Individual patient data meta\u2010analysis was performed using patient\u2010level data combined from six 26\u2010week, phase\u2010<jats:styled-content style=\"fixed-case\">III<\/jats:styled-content>, randomised controlled T2D trials, which comprise the \u2018Liraglutide Effect and Action in Diabetes\u2019 (<jats:styled-content style=\"fixed-case\">LEAD<\/jats:styled-content>) program. The <jats:styled-content style=\"fixed-case\">LEAD<\/jats:styled-content>\u20102 sub\u2010study was analysed to assess the effect on <jats:styled-content style=\"fixed-case\">CT<\/jats:styled-content>\u2010measured hepatic steatosis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Of 4442 patients analysed, 2241 (50.8%) patients had an abnormal <jats:styled-content style=\"fixed-case\">ALT<\/jats:styled-content> at baseline [mean <jats:styled-content style=\"fixed-case\">ALT<\/jats:styled-content> 33.8(14.9)\u00a0<jats:styled-content style=\"fixed-case\">IU<\/jats:styled-content>\/L in females; 47.3(18.3)\u00a0<jats:styled-content style=\"fixed-case\">IU<\/jats:styled-content>\/L in males]. Liraglutide 1.8\u00a0mg reduced <jats:styled-content style=\"fixed-case\">ALT<\/jats:styled-content> in these patients vs. placebo (\u22128.20 vs. \u22125.01\u00a0<jats:styled-content style=\"fixed-case\">IU<\/jats:styled-content>\/L; <jats:italic>P<\/jats:italic>\u00a0=\u00a00.003), and was dose\u2010dependent (no significant differences vs. placebo with liraglutide 0.6 or 1.2\u00a0mg). This effect was lost after adjusting for liraglutide's reduction in weight (mean <jats:styled-content style=\"fixed-case\">ALT<\/jats:styled-content> difference vs. placebo \u22121.41\u00a0<jats:styled-content style=\"fixed-case\">IU<\/jats:styled-content>\/L, <jats:italic>P\u00a0<\/jats:italic>=\u00a00.21) and HbA1c (+0.57\u00a0<jats:styled-content style=\"fixed-case\">IU<\/jats:styled-content>\/L, <jats:italic>P\u00a0<\/jats:italic>=\u00a00.63). Adverse effects with 1.8\u00a0mg liraglutide were similar between patients with and without baseline abnormal <jats:styled-content style=\"fixed-case\">ALT<\/jats:styled-content>. In <jats:styled-content style=\"fixed-case\">LEAD<\/jats:styled-content>\u20102 sub\u2010study, liraglutide 1.8\u00a0mg showed a trend towards improving hepatic steatosis vs. placebo (liver\u2010to\u2010spleen attenuation ratio +0.10 vs. 0.00; <jats:italic>P\u00a0<\/jats:italic>=\u00a00.07). This difference was reduced when correcting for changes in weight (+0.06, <jats:italic>P\u00a0<\/jats:italic>=\u00a00.25) and HbA<jats:sub>1c<\/jats:sub> (0.00, <jats:italic>P\u00a0<\/jats:italic>=\u00a00.93).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Twenty\u2010six weeks' liraglutide 1.8\u00a0mg is safe, well tolerated and improves liver enzymes in patients with type 2 diabetes. This effect appears to be mediated by its action on weight loss and glycaemic control.<\/jats:p><\/jats:sec>","DOI":"10.1111\/apt.12149","type":"journal-article","created":{"date-parts":[[2012,11,20]],"date-time":"2012-11-20T04:35:37Z","timestamp":1353386137000},"page":"234-242","source":"Crossref","is-referenced-by-count":218,"title":["Safety and efficacy of liraglutide in patients with type 2 diabetes and elevated liver enzymes: individual patient data meta\u2010analysis of the LEAD program"],"prefix":"10.1111","volume":"37","author":[{"given":"M. J.","family":"Armstrong","sequence":"first","affiliation":[{"name":"Centre for Liver Research and NIHR Liver Biomedical Research Unit University of Birmingham Birmingham UK"},{"name":"Liver Unit Queen Elizabeth University Hospital Birmingham Birmingham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D. D.","family":"Houlihan","sequence":"additional","affiliation":[{"name":"Centre for Liver Research and NIHR Liver Biomedical Research Unit University of Birmingham Birmingham UK"},{"name":"Liver Unit Queen Elizabeth University Hospital Birmingham Birmingham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I. A.","family":"Rowe","sequence":"additional","affiliation":[{"name":"Centre for Liver Research and NIHR Liver Biomedical Research Unit University of Birmingham Birmingham UK"},{"name":"Liver Unit Queen Elizabeth University Hospital Birmingham Birmingham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W. H. O.","family":"Clausen","sequence":"additional","affiliation":[{"name":"Statistics Larix A\/S Ballerup Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B.","family":"Elbr\u00f8nd","sequence":"additional","affiliation":[{"name":"Global Medical Affairs Novo Nordisk A\/S Soeborg Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S. C. L.","family":"Gough","sequence":"additional","affiliation":[{"name":"Oxford Centre for Diabetes Endocrinology and Metabolism and NIHR Oxford Biomedical Research Centre Churchill Hospital Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. W.","family":"Tomlinson","sequence":"additional","affiliation":[{"name":"Centre for Endocrinology Diabetes and Metabolism University of Birmingham Birmingham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P. 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