{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T22:55:53Z","timestamp":1772578553802,"version":"3.50.1"},"reference-count":16,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,3,10]],"date-time":"2021-03-10T00:00:00Z","timestamp":1615334400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2021,3,10]],"date-time":"2021-03-10T00:00:00Z","timestamp":1615334400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Diabetol Metab Syndr"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Dipeptidyl peptidase 4 (DPP4) is a serine exopeptidase able to inactivate various oligopeptides, and also a hepatokine. Hepatocyte-specific overexpression of DPP4 is associated with hepatic insulin resistance and liver steatosis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Method<\/jats:title>\n                    <jats:p>We examined whether weekly DPP4 inhibitor omarigliptin (OMG) can improve liver function as well as levels of inflammation and insulin resistance in type 2 diabetic patients with non-alcoholic fatty liver disease (NAFLD). Further, we investigated the effects of OMG in a diabetic patient with biopsy-confirmed nonalcoholic steatohepatitis (NASH).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In NAFLD patients, OMG significantly decreased levels of aminotransferase, aspartate aminotransferase, gamma-glutamyl transpeptidase, homeostatic model assessment of insulin resistance (HOMA-IR), and high-sensitivity C-reactive protein (hsCRP), while no significant change was seen in hemoglobin A1c or body mass index. In the NASH patient, liver function improved markedly, and levels of the hepatic fibrosis marker FIB-4 decreased in parallel with HOMA-IR and hsCRP. Slight but clear improvements in intrahepatic fat deposition and fibrosis appeared to be seen on diagnostic ultrasonography.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Weekly administration of the DPP4 inhibitor OMG in ameliorating hepatic insulin resistance may cause beneficial effects in liver with NAFLD\/NASH.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13098-021-00644-5","type":"journal-article","created":{"date-parts":[[2021,3,10]],"date-time":"2021-03-10T06:04:04Z","timestamp":1615356244000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Beneficial effect of omarigliptin on diabetic patients with non-alcoholic fatty liver disease\/non-alcoholic steatohepatitis"],"prefix":"10.1186","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4580-4382","authenticated-orcid":false,"given":"Sachiko","family":"Hattori","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kazuomi","family":"Nomoto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tomohiko","family":"Suzuki","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seishu","family":"Hayashi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2021,3,10]]},"reference":[{"key":"644_CR1","doi-asserted-by":"publisher","first-page":"60","DOI":"10.1186\/s13098-020-00570-y","volume":"12","author":"AF Godoy-Matos","year":"2020","unstructured":"Godoy-Matos AF, Silva J\u00fanior WS, Valerio CM. NAFLD as a continuum: from obesity to metabolic syndrome and diabetes. Diabetol Metab Syndr. 2020;12:60. https:\/\/doi.org\/10.1186\/s13098-020-00570-y (eCollection 2020).","journal-title":"Diabetol Metab Syndr."},{"issue":"6","key":"644_CR2","doi-asserted-by":"publisher","first-page":"499","DOI":"10.21037\/hbsn.2018.10.05","volume":"7","author":"WS Silva J\u00fanior","year":"2018","unstructured":"Silva J\u00fanior WS, Souza MDGC, Kraemer-Aguiar LG. Dipeptidyl peptidase 4 (DPP4), adipose inflammation, and insulin resistance: is it time to look to the hepatocyte? Hepatobiliary Surg Nutr. 2018;7(6):499\u2013500.","journal-title":"Hepatobiliary Surg Nutr"},{"key":"644_CR3","doi-asserted-by":"publisher","first-page":"5238013","DOI":"10.1155\/2019\/5238013","volume":"2019","author":"WS Silva J\u00fanior","year":"2019","unstructured":"Silva J\u00fanior WS, Souza MDGC, Nogueira Neto JF, et al. Dipeptidyl peptidase 4 activity is related to body composition, measures of adiposity, and insulin resistance in subjects with excessive adiposity and different degrees of glucose tolerance. J Diabetes Res. 2019;2019:5238013.","journal-title":"J Diabetes Res"},{"key":"644_CR4","doi-asserted-by":"publisher","first-page":"673","DOI":"10.1038\/nature26138","volume":"555","author":"DS Ghorpade","year":"2018","unstructured":"Ghorpade DS, Ozcan L, Zheng Z, et al. Hepatocyte-secreted DPP4 in obesity promotes adipose inflammation and insulin resistance. Nature. 2018;555:673\u20137.","journal-title":"Nature"},{"key":"644_CR5","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1186\/s13098-020-00533-3","volume":"12","author":"S Hattori","year":"2020","unstructured":"Hattori S. Omarigliptin decreases inflammation and insulin resistance in a pleiotropic manner in patients with type 2 diabetes. Diabetol Metab Syndr. 2020;12:24. https:\/\/doi.org\/10.1186\/s13098-020-00533-3.","journal-title":"Diabetol Metab Syndr."},{"key":"644_CR6","doi-asserted-by":"publisher","first-page":"1254","DOI":"10.1016\/j.molmet.2017.07.016","volume":"6","author":"C Baumeier","year":"2017","unstructured":"Baumeier C, Schl\u00fcter L, Saussenthaler S, et al. Elevated hepatic DPP4 activity promotes insulin resistance and non-alcoholic fatty liver disease. Mol Metab. 2017;6:1254\u201363. https:\/\/doi.org\/10.1016\/j.molmet.2017.07.016.","journal-title":"Mol Metab"},{"key":"644_CR7","doi-asserted-by":"publisher","first-page":"1317","DOI":"10.1002\/hep.21178","volume":"43","author":"RK Sterling","year":"2006","unstructured":"Sterling RK, Lissen E, Clumeck N, et al. Development of a simple noninvasive index to predict significant fibrosis in patients with HIV\/HCV coinfection. Hepatology. 2006;43:1317\u201325.","journal-title":"Hepatology"},{"key":"644_CR8","unstructured":"Omarigliptin Pharmaceutical interview form 2016; 4th edition."},{"key":"644_CR9","doi-asserted-by":"publisher","first-page":"E506","DOI":"10.1152\/ajpendo.00586.2009","volume":"299","author":"N Kl\u00f6ting","year":"2010","unstructured":"Kl\u00f6ting N, Fasshauer M, Dietrich A, et al. Insulin-sensitive obesity. Am J Physiol Endocrinol Metab. 2010;299:E506\u201315.","journal-title":"Am J Physiol Endocrinol Metab"},{"key":"644_CR10","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1002\/hep.28431","volume":"64","author":"ZM Younossi","year":"2016","unstructured":"Younossi ZM, Koenig AB, Abdelatif D, et al. Global epidemiology of nonalcoholic fatty liver disease-Meta-analytic assessment of prevalence, incidence, and outcomes. 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Cell Metab. 2018;29:320\u201334. https:\/\/doi.org\/10.1016\/j.cmet.2018.10.001.","journal-title":"Cell Metab"},{"key":"644_CR13","doi-asserted-by":"publisher","first-page":"1917","DOI":"10.2337\/db10-1707","volume":"60","author":"D Lamers","year":"2011","unstructured":"Lamers D, Famulla S, Wronkowitz N, et al. Dipeptidyl peptidase 4 is a novel adipokine potentially linking obesity to the metabolic syndrome. Diabetes. 2011;60:1917\u201325.","journal-title":"Diabetes"},{"issue":"3","key":"644_CR14","doi-asserted-by":"publisher","first-page":"348","DOI":"10.1016\/j.bbrc.2016.02.019","volume":"471","author":"D R\u00f6hrborn","year":"2016","unstructured":"R\u00f6hrborn D, Br\u00fcckner J, Sell H, Eckel J. Reduced DPP4 activity improves insulin signaling in primary human adipocytes. Biochem Biophys Res Commun. 2016;471(3):348\u201354.","journal-title":"Biochem Biophys Res Commun."},{"key":"644_CR15","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1002\/hep4.1019","volume":"27","author":"N Akuta","year":"2017","unstructured":"Akuta N, Watanabe C, Kawamura Y, et al. Effect of sodium-glucose cotransporter 2 inhibitor in nonalcoholic fatty liver disease complicated by diabetes mellitus: preliminary prospective study based on serial liver biopsies. Hepatol Commun. 2017;27:46\u201352.","journal-title":"Hepatol Commun"},{"key":"644_CR16","doi-asserted-by":"publisher","first-page":"284","DOI":"10.1016\/j.clinre.2016.11.009","volume":"41","author":"Y Dong","year":"2017","unstructured":"Dong Y, Lv Q, Li S, et al. Efficacy and safety of glucagon-like peptide-1 receptor agonists in non-alcoholic fatty liver disease: a systemic review and meta-analysis. Clin Res Hepatol Gastroenterol. 2017;41:284\u201395.","journal-title":"Clin Res Hepatol Gastroenterol"}],"container-title":["Diabetology &amp; Metabolic Syndrome"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s13098-021-00644-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1186\/s13098-021-00644-5\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s13098-021-00644-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,3,10]],"date-time":"2021-03-10T06:17:50Z","timestamp":1615357070000},"score":1,"resource":{"primary":{"URL":"https:\/\/dmsjournal.biomedcentral.com\/articles\/10.1186\/s13098-021-00644-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3,10]]},"references-count":16,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2021,12]]}},"alternative-id":["644"],"URL":"https:\/\/doi.org\/10.1186\/s13098-021-00644-5","relation":{"has-preprint":[{"id-type":"doi","id":"10.21203\/rs.3.rs-128674\/v1","asserted-by":"object"}]},"ISSN":["1758-5996"],"issn-type":[{"value":"1758-5996","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,3,10]]},"assertion":[{"value":"8 December 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 February 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 March 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The case study was approved by the ethics committee at Tohto Clinic, and written informed consent was obtained from the patient in this study.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"All authors participated in drafting this article and gave final approval of the version to be submitted.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"28"}}