{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T20:43:40Z","timestamp":1791319420011,"version":"4.3.1"},"reference-count":43,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"16","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2020,8,18]]},"abstract":"<jats:sec xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">Epeleuton is 15\u2010hydroxy eicosapentaenoic acid ethyl ester, a second\u2010generation synthetic n\u20103 fatty acid derivative of eicosapentaenoic acid. The primary objective was to assess the effect of epeleuton on markers of nonalcoholic fatty liver disease (NAFLD) with post hoc analyses of cardiometabolic markers.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Methods and Results<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              In a multicenter, randomized, double\u2010blind, placebo\u2010controlled trial, 96 adults with nonalcoholic fatty liver disease and body mass index 25 to 40 were randomized in a 1:1:1 ratio to receive epeleuton 2\u00a0g\/day, epeleuton 1\u00a0g\/day, or placebo for 16\u00a0weeks. A total of 27% of patients had diabetes mellitus. Primary end points of changes in alanine aminotransferase and liver stiffness did not improve at week 16. Secondary and post hoc analyses investigated changes in cardiometabolic markers. Epeleuton 2\u00a0g\/day significantly decreased triglycerides, very\u2010low\u2010density lipoprotein cholesterol, and total cholesterol without increasing low\u2010density lipoprotein cholesterol. Despite a low mean baseline hemoglobin A1C (HbA\n              <jats:sub>1C<\/jats:sub>\n              ; 6.3\u00b11.3%), epeleuton 2\u00a0g\/day significantly decreased HbA\n              <jats:sub>1c<\/jats:sub>\n              (\u22120.4%;\n              <jats:italic>P<\/jats:italic>\n              =0.026). Among patients with baseline HbA\n              <jats:sub>1c<\/jats:sub>\n              &gt;6.5%, epeleuton 2\u00a0g\/day decreased HbA\n              <jats:sub>1c<\/jats:sub>\n              by 1.1% (\n              <jats:italic>P<\/jats:italic>\n              =0.047; n=26). Consistent dose\u2010dependent reductions were observed for fasting plasma glucose, insulin, and insulin resistance indices. Epeleuton 2\u00a0g\/day decreased circulating markers of cardiovascular risk and endothelial dysfunction. Epeleuton was well tolerated, with a safety profile not different from placebo.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              While epeleuton did not meet its primary end points on alanine aminotransferase or liver stiffness, it significantly decreased triglycerides, HbA\n              <jats:sub>1C<\/jats:sub>\n              , plasma glucose, and inflammatory markers. These data suggest epeleuton may have potential for cardiovascular risk reduction and nonalcoholic fatty liver disease by simultaneously targeting hypertriglyceridemia, hyperglycemia, and systemic inflammation. Further trials are planned.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Registration<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              URL:\n              <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/www.clinicaltrials.gov\">https:\/\/www.clini\u200bcaltr\u200bials.gov<\/jats:ext-link>\n              ; Unique identifier: NCT02941549.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.119.016334","type":"journal-article","created":{"date-parts":[[2020,8,11]],"date-time":"2020-08-11T09:15:30Z","timestamp":1597137330000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":25,"title":["Effects of Epeleuton, a Novel Synthetic Second\u2010Generation n\u20103 Fatty Acid, on Non\u2010Alcoholic Fatty Liver Disease, Triglycerides, Glycemic Control, and Cardiometabolic and Inflammatory Markers"],"prefix":"10.1161","volume":"9","author":[{"given":"John","family":"Climax","sequence":"first","affiliation":[{"name":"Afimmune Dublin Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip N.","family":"Newsome","sequence":"additional","affiliation":[{"name":"National Institute for Health Research Biomedical Research Centre at University Hospitals Birmingham NHS Foundation Trust and the University of Birmingham United Kingdom"},{"name":"Centre for Liver and Gastrointestinal Research Institute of Immunology and Immunotherapy University of Birmingham United Kingdom"},{"name":"Liver Unit University Hospitals Birmingham NHS Foundation Trust Birmingham United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4139-2464","authenticated-orcid":false,"given":"Moayed","family":"Hamza","sequence":"additional","affiliation":[{"name":"Afimmune Dublin Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus","family":"Weissbach","sequence":"additional","affiliation":[{"name":"Afimmune Dublin Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Coughlan","sequence":"additional","affiliation":[{"name":"Afimmune Dublin Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1604-2593","authenticated-orcid":false,"given":"Naveed","family":"Sattar","sequence":"additional","affiliation":[{"name":"Institute of Cardiovascular and Medical Sciences University of Glasgow United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darren K.","family":"McGuire","sequence":"additional","affiliation":[{"name":"University of Texas Southwestern Medical Center Dallas TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1278-6245","authenticated-orcid":false,"given":"Deepak L.","family":"Bhatt","sequence":"additional","affiliation":[{"name":"Brigham and Women\u2019s Hospital Heart &amp; Vascular Center Harvard Medical School Boston MA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.g4596"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.115.307611"},{"key":"e_1_3_2_4_2","first-page":"117","article-title":"Global, regional, and national age\u2013sex specific all\u2010cause and cause\u2010specific mortality for 240 causes of death, 1990\u20132013: a systematic analysis for the Global Burden of Disease Study 2013","author":"Anon","year":"2015","unstructured":"Anon . 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