{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T12:18:07Z","timestamp":1787833087708,"version":"build-2784847793"},"reference-count":15,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T00:00:00Z","timestamp":1786406400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T00:00:00Z","timestamp":1786406400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Liver International"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    The patatin\u2010like phospholipase 3 (PNPLA3) I148M genetic variant is highly associated with steatotic liver disease. In the SURPASS\u20103 MRI substudy, tirzepatide significantly reduced liver fat content (LFC) versus insulin degludec in insulin\u2010na\u00efve patients with type 2 diabetes with metabolic dysfunction\u2010associated steatotic liver disease. The influence of PNPLA3 I148M allele on changes in LFC in response to tirzepatide is unknown. This post hoc analysis evaluated changes in MRI\u2010assessed LFC\u00a0and cardiometabolic parameters by presence (genotypes GG and CG) or absence (genotype CC) of the PNPLA3 I148M\u00a0allele after 52\u2010week treatment. Tirzepatide\u2010treated participants experienced significant reductions in LFC, weight, HbA\n                    <jats:sub>1c<\/jats:sub>\n                    , and overall greater improvement in lipids and liver enzymes regardless of the presence of PNPLA3 I148M allele. Findings were consistent across genotype subgroups. In this exploratory analysis, the presence of PNPLA3 I148M allele did not seem to affect tirzepatide\u2010induced improvement in LFC and several cardiometabolic parameters in patients with type 2 diabetes.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Trial Registration:<\/jats:bold>\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/clinicaltrials.gov\">ClinicalTrials.gov<\/jats:ext-link>\n                    identifier: NCT03882970\n                  <\/jats:p>","DOI":"10.1111\/liv.70837","type":"journal-article","created":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T07:21:29Z","timestamp":1786432889000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Liver Fat Changes in Patients With Type 2 Diabetes by Presence of Genetic Hepatic Steatosis: A Post Hoc Analysis of\n                    <scp>SURPASS<\/scp>\n                    \u20103\n                    <scp>MRI<\/scp>"],"prefix":"10.1111","volume":"46","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8629-418X","authenticated-orcid":false,"given":"Kenneth","family":"Cusi","sequence":"first","affiliation":[{"name":"Division of Endocrinology, Diabetes and Metabolism The University of Florida  Gainesville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2594-1651","authenticated-orcid":false,"given":"Amalia","family":"Gastaldelli","sequence":"additional","affiliation":[{"name":"Institute of Clinical Physiology, CNR  Pisa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura Fern\u00e1ndez","family":"Land\u00f3","sequence":"additional","affiliation":[{"name":"Eli Lilly and Company  Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Palash","family":"Sharma","sequence":"additional","affiliation":[{"name":"Eli Lilly and Company  Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3276-1296","authenticated-orcid":false,"given":"Amelia","family":"Torcello\u2010G\u00f3mez","sequence":"additional","affiliation":[{"name":"Eli Lilly and Company  Cork Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8721-9539","authenticated-orcid":false,"given":"\u00c1ngel","family":"Rodr\u00edguez","sequence":"additional","affiliation":[{"name":"Lilly Spain  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,11]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.50.8.1844"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.2337\/dci24\u20100094"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.2337\/dci22\u20100034"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc26\u2010S004"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.257"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(21)01443-4"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2213\u20108587(22)00070\u20105"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2213\u20108587(22)00077\u20108"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.2337\/db23\u2010759\u2010P"},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/jgh.12656"},{"key":"e_1_2_13_12_1","doi-asserted-by":"publisher","DOI":"10.3945\/ajcn.111.012369"},{"key":"e_1_2_13_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/hepr.12552"},{"key":"e_1_2_13_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125\u2010018\u20104675\u20102"},{"key":"e_1_2_13_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12020\u2010020\u201002470\u20107"},{"key":"e_1_2_13_16_1","doi-asserted-by":"publisher","DOI":"10.1097\/HEP.0000000000001193"}],"container-title":["Liver International"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/liv.70837","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/liv.70837","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/liv.70837","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T11:24:23Z","timestamp":1787829863000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/liv.70837"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,11]]},"references-count":15,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2026,9]]}},"alternative-id":["10.1111\/liv.70837"],"URL":"https:\/\/doi.org\/10.1111\/liv.70837","archive":["Portico"],"relation":{},"ISSN":["1478-3223","1478-3231"],"issn-type":[{"value":"1478-3223","type":"print"},{"value":"1478-3231","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,11]]},"assertion":[{"value":"2025-11-25","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-30","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-11","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70837"}}