{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T05:08:59Z","timestamp":1793164139535,"version":"4.5.0"},"reference-count":59,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T00:00:00Z","timestamp":1782172800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T00:00:00Z","timestamp":1782172800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100004312","name":"Eli Lilly and Company","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004312","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["dom-pubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Diabetes Obesity Metabolism"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Orforglipron is a novel small\u2010molecule, once daily oral non\u2010peptide GLP\u20101 receptor agonist. The hepatic safety profile in adults with obesity or overweight and\/or type 2 diabetes (T2D) across seven orforglipron Phase 3 clinical trials was assessed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods<\/jats:title>\n                    <jats:p>\n                      Overall, 11\u2009220 participants were included in this analysis (orforglipron\n                      <jats:italic>N<\/jats:italic>\n                      \u2009=\u20096920; pooled comparator [placebo, oral semaglutide, dapagliflozin, insulin glargine]\n                      <jats:italic>N<\/jats:italic>\n                      \u2009=\u20094300) for up to 104\u2009weeks, including safety follow\u2010up. Eligibility criteria for these Phase 3 trials included ALT\/AST &lt;\u20093\u2009\u00d7\u2009ULN in the weight management programme and \u2264\u20095\u2009\u00d7\u2009ULN in the T2D programme. The main analysis sets included placebo\u2010controlled trials by indication for pooled orforglipron doses. Changes from baseline in hepatic analytes were assessed continuously and categorically, and screening for drug\u2010induced liver injury\/Hy's Law was conducted. Hepatic AEs were summarised. Subgroup analyses were conducted in participants with elevated baseline aminotransferases.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Orforglipron treatment was associated with mean reductions in ALT\/AST. Categorical ALT\/AST elevations were generally balanced between orforglipron and comparators. Six (0.1%) orforglipron\u2010treated participants and six (0.1%) comparator\u2010treated participants had ALT or AST \u2265\u20093\u2009\u00d7\u2009ULN and TBIL \u2265\u20092\u2009\u00d7\u2009ULN; however, alternative etiologies accounted for all orforglipron cases and thus did not meet criteria for drug induced liver injury\/Hy's Law. The incidence of hepatic AEs was balanced between orforglipron and pooled comparators, suggesting no increased risk with orforglipron. Results were consistent in participants with normal and elevated baseline aminotransferases.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>In this pooled analysis of orforglipron Phase 3 clinical trials, orforglipron treatment was not associated with drug\u2010induced liver injury, demonstrating a hepatic safety profile similar to placebo or active comparators. There were no cases consistent with drug\u2010induced liver injury\/Hy's Law with orforglipron. Aminotransferase trajectories showed a hepatic profile consistent with the metabolic benefits of weight loss.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/dom.71032","type":"journal-article","created":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T04:36:10Z","timestamp":1782275770000},"page":"8347-8358","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Hepatic Safety of Orforglipron in Adults With Obesity or Overweight and\/or Type 2 Diabetes: A Pooled Analysis of the Orforglipron Phase 3 Clinical Trials"],"prefix":"10.1111","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0111-1530","authenticated-orcid":false,"given":"Sean","family":"Wharton","sequence":"first","affiliation":[{"name":"University of Toronto, and Wharton Weight Management Clinic  Toronto Ontario 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Asare","family":"Twum","sequence":"additional","affiliation":[{"name":"Eli Lilly and Company  Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6215-6885","authenticated-orcid":false,"given":"Max","family":"Denning","sequence":"additional","affiliation":[{"name":"Eli Lilly and Company  Indianapolis Indiana 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