{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,18]],"date-time":"2026-01-18T01:28:02Z","timestamp":1768699682188,"version":"3.49.0"},"reference-count":20,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2023,10,26]],"date-time":"2023-10-26T00:00:00Z","timestamp":1698278400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2023,10,26]],"date-time":"2023-10-26T00:00:00Z","timestamp":1698278400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Diabetol Metab Syndr"],"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Pemafibrate has been reported to ameliorate lipid profiles and liver dysfunction. However, which patients derive benefit from the hepatoprotective effects of pemafibrate is unclear.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>We conducted a sub-analysis of the PARM-T2D study where subjects with type 2 diabetes complicated by hypertriglyceridemia were prospectively treated with pemafibrate or conventional therapies for 52 weeks. From the original cohort, subjects who had metabolic-associated fatty liver disease without changing their treatment regimens for comorbidities were analyzed. Eligible subjects (n\u2009=\u2009293) (average age 61.2\u2009\u00b1\u200911.7 years, 37.5% female) treated with pemafibrate (pemafibrate, n\u2009=\u2009152) or controls who did not change their treatment regimens (controls, n\u2009=\u2009141) were divided into three groups based on their alanine aminotransferase (ALT) levels: ALT\u2009\u2264\u2009upper normal limit (UNL) (pemafibrate, n\u2009=\u200965; controls, n\u2009=\u200950), UNL\u2009&lt;\u2009ALT\u2009\u2264\u20092\u00d7UNL (pemafibrate, n\u2009=\u200958; controls, n\u2009=\u200954), and 2\u00d7UNL\u2009&lt;\u2009ALT (pemafibrate, n\u2009=\u200929; controls, n\u2009=\u200927).<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Pemafibrate treatment significantly ameliorated ALT levels (from 29 to 22 U\/L, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001 by Wilcoxon\u2019s signed-rank test) in the total cohort and subjects with high ALT levels (2\u00d7ULN\u2009&lt;\u2009ALT), and improved liver fibrosis as assessed by the Fibrosis-4 index (mean change \u2212\u20090.05 (95% confidence interval: \u22120.22 to \u2212\u20090.02), <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05 versus baseline by the Mann-Whitney <jats:italic>U<\/jats:italic>-test and <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05 versus the ALT\u2009\u2264\u2009UNL group by the Kruskal\u2013Wallis test followed by Dunn\u2019s post-hoc analysis).<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>The hepatoprotective effects of pemafibrate were dominant in subjects with type 2 diabetes complicated with liver dysfunction.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Trial registration<\/jats:title>\n                <jats:p>This study was registered with the University Hospital Medical Information Network Center Clinical Trials Registry (UMIN000037385).<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s13098-023-01187-7","type":"journal-article","created":{"date-parts":[[2023,10,26]],"date-time":"2023-10-26T02:02:14Z","timestamp":1698285734000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Preferable effects of pemafibrate on liver function and fibrosis in subjects with type 2 diabetes complicated with liver damage"],"prefix":"10.1186","volume":"15","author":[{"given":"Hiroshi","family":"Nomoto","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kenichi","family":"Kito","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroshi","family":"Iesaka","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takahisa","family":"Handa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shingo","family":"Yanagiya","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aika","family":"Miya","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiraku","family":"Kameda","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kyu Yong","family":"Cho","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jun","family":"Takeuchi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"So","family":"Nagai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ichiro","family":"Sakuma","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Akinobu","family":"Nakamura","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tatsuya","family":"Atsumi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2023,10,26]]},"reference":[{"key":"1187_CR1","doi-asserted-by":"publisher","first-page":"1020","DOI":"10.1111\/jdi.13306","volume":"11","author":"E Araki","year":"2020","unstructured":"Araki E, et al. Japanese clinical practice Guideline for Diabetes 2019. J Diabetes Investig. 2020;11:1020\u201376.","journal-title":"J Diabetes Investig"},{"key":"1187_CR2","doi-asserted-by":"publisher","first-page":"889","DOI":"10.1007\/s12072-020-10094-2","volume":"14","author":"M Eslam","year":"2020","unstructured":"Eslam M, et al. The Asian Pacific Association for the study of the liver clinical practice guidelines for the diagnosis and management of metabolic associated fatty Liver Disease. Hepatol Int. 2020;14:889\u2013919.","journal-title":"Hepatol Int"},{"key":"1187_CR3","doi-asserted-by":"publisher","first-page":"1559","DOI":"10.1056\/NEJMoa2029349","volume":"385","author":"AJ Sanyal","year":"2021","unstructured":"Sanyal AJ, et al. Prospective study of outcomes in adults with nonalcoholic fatty Liver Disease. N Engl J Med. 2021;385:1559\u201369.","journal-title":"N Engl J Med"},{"key":"1187_CR4","doi-asserted-by":"publisher","first-page":"548","DOI":"10.1111\/hepr.12384","volume":"45","author":"T Shima","year":"2015","unstructured":"Shima T, et al. Influence of lifestyle-related Diseases and age on the development and progression of non-alcoholic fatty Liver Disease. Hepatol Res. 2015;45:548\u201359.","journal-title":"Hepatol Res"},{"key":"1187_CR5","doi-asserted-by":"crossref","unstructured":"Guti\u00e9rrez-Cuevas J, Santos A, Armendariz-Borunda J. Pathophysiological molecular mechanisms of obesity: a link between MAFLD and NASH with Cardiovascular Diseases. Int J Mol Sci. 2021;22.","DOI":"10.3390\/ijms222111629"},{"key":"1187_CR6","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1016\/j.atherosclerosis.2016.02.029","volume":"249","author":"S Ishibashi","year":"2016","unstructured":"Ishibashi S, et al. Effects of K-877, a novel selective PPAR\u03b1 modulator (SPPARM\u03b1), in dyslipidaemic patients: a randomized, double blind, active- and placebo-controlled, phase 2 trial. Atherosclerosis. 2016;249:36\u201343.","journal-title":"Atherosclerosis"},{"key":"1187_CR7","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1016\/j.jacl.2017.10.006","volume":"12","author":"S Ishibashi","year":"2018","unstructured":"Ishibashi S, et al. Efficacy and safety of pemafibrate (K-877), a selective peroxisome proliferator-activated receptor \u03b1 modulator, in patients with dyslipidemia: results from a 24-week, randomized, double blind, active-controlled, phase 3 trial. J Clin Lipidol. 2018;12:173\u201384.","journal-title":"J Clin Lipidol"},{"key":"1187_CR8","doi-asserted-by":"publisher","first-page":"110091","DOI":"10.1016\/j.diabres.2022.110091","volume":"192","author":"K Kito","year":"2022","unstructured":"Kito K, et al. Effects of pemafibrate on lipid metabolism in patients with type 2 Diabetes and hypertriglyceridemia: a multi-center prospective observational study, the PARM-T2D study. Diabetes Res Clin Pract. 2022;192:110091.","journal-title":"Diabetes Res Clin Pract"},{"key":"1187_CR9","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1186\/1471-230X-6-33","volume":"6","author":"G Bedogni","year":"2006","unstructured":"Bedogni G, et al. The fatty liver index: a simple and accurate predictor of hepatic steatosis in the general population. BMC Gastroenterol. 2006;6:33.","journal-title":"BMC Gastroenterol"},{"key":"1187_CR10","doi-asserted-by":"publisher","first-page":"1317","DOI":"10.1002\/hep.21178","volume":"43","author":"RK Sterling","year":"2006","unstructured":"Sterling RK, 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":"1187_CR11","doi-asserted-by":"publisher","first-page":"82","DOI":"10.1186\/1475-2840-12-82","volume":"12","author":"JC Fruchart","year":"2013","unstructured":"Fruchart JC. Selective peroxisome proliferator-activated receptor \u03b1 modulators (SPPARM\u03b1): the next generation of peroxisome proliferator-activated receptor \u03b1-agonists. Cardiovasc Diabetol. 2013;12:82.","journal-title":"Cardiovasc Diabetol"},{"key":"1187_CR12","doi-asserted-by":"publisher","first-page":"755","DOI":"10.1530\/EC-20-0152","volume":"9","author":"H Keinicke","year":"2020","unstructured":"Keinicke H, et al. FGF21 regulates hepatic metabolic pathways to improve steatosis and inflammation. Endocr Connect. 2020;9:755\u201368.","journal-title":"Endocr Connect"},{"key":"1187_CR13","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1186\/s12933-021-01291-w","volume":"20","author":"K Yokote","year":"2021","unstructured":"Yokote K, et al. Effects of pemafibrate on glucose metabolism markers and liver function tests in patients with hypertriglyceridemia: a pooled analysis of six phase 2 and phase 3 randomized double-blind placebo-controlled clinical trials. Cardiovasc Diabetol. 2021;20:96.","journal-title":"Cardiovasc Diabetol"},{"key":"1187_CR14","doi-asserted-by":"publisher","first-page":"270","DOI":"10.5114\/ceh.2020.99528","volume":"6","author":"S Shinozaki","year":"2020","unstructured":"Shinozaki S, Tahara T, Lefor AK, Ogura M. Pemafibrate decreases markers of hepatic inflammation in patients with non-alcoholic fatty Liver Disease. Clin Exp Hepatol. 2020;6:270\u20134.","journal-title":"Clin Exp Hepatol"},{"key":"1187_CR15","doi-asserted-by":"publisher","first-page":"172","DOI":"10.5114\/ceh.2021.106864","volume":"7","author":"S Shinozaki","year":"2021","unstructured":"Shinozaki S, Tahara T, Lefor AK, Ogura M. Pemafibrate improves hepatic inflammation, function and fibrosis in patients with non-alcoholic fatty Liver Disease: a one-year observational study. Clin Exp Hepatol. 2021;7:172\u20137.","journal-title":"Clin Exp Hepatol"},{"key":"1187_CR16","doi-asserted-by":"publisher","first-page":"1263","DOI":"10.1111\/apt.16596","volume":"54","author":"A Nakajima","year":"2021","unstructured":"Nakajima A, et al. Randomised clinical trial: Pemafibrate, a novel selective peroxisome proliferator-activated receptor \u03b1 modulator (SPPARM\u03b1), versus placebo in patients with non-alcoholic fatty Liver Disease. Aliment Pharmacol Ther. 2021;54:1263\u201377.","journal-title":"Aliment Pharmacol Ther"},{"key":"1187_CR17","doi-asserted-by":"publisher","first-page":"2996","DOI":"10.1038\/s41598-022-06542-8","volume":"12","author":"K Kanno","year":"2022","unstructured":"Kanno K, et al. Pemafibrate suppresses NLRP3 inflammasome activation in the liver and heart in a novel mouse model of steatohepatitis-related cardiomyopathy. Sci Rep. 2022;12:2996.","journal-title":"Sci Rep"},{"key":"1187_CR18","doi-asserted-by":"publisher","first-page":"1094100","DOI":"10.3389\/fcvm.2023.1094100","volume":"10","author":"Y Takeda","year":"2023","unstructured":"Takeda Y, et al. The effects of pemafibrate and omega-3 fatty acid ethyl on apoB-48 in dyslipidemic patients treated with statin: a prospective, multicenter, open-label, randomized, parallel group trial in Japan (PROUD48 study). Front Cardiovasc Med. 2023;10:1094100.","journal-title":"Front Cardiovasc Med"},{"key":"1187_CR19","doi-asserted-by":"publisher","first-page":"e21162","DOI":"10.1097\/MD.0000000000021162","volume":"99","author":"HW Hwang","year":"2020","unstructured":"Hwang HW, Yu JH, Jin YJ, Suh YJ, Lee JW. Correlation between the small dense LDL level and nonalcoholic fatty Liver Disease: possibility of a new biomarker. Med (Baltim). 2020;99:e21162.","journal-title":"Med (Baltim)"},{"key":"1187_CR20","doi-asserted-by":"publisher","first-page":"e30527","DOI":"10.1097\/MD.0000000000030527","volume":"101","author":"S Young Kim","year":"2022","unstructured":"Young Kim S, et al. Association between small dense LDL levels and hepatic fibrosis in patients with nonalcoholic fatty Liver Disease. Med (Baltim). 2022;101:e30527.","journal-title":"Med (Baltim)"}],"container-title":["Diabetology &amp; Metabolic Syndrome"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13098-023-01187-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s13098-023-01187-7\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13098-023-01187-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,20]],"date-time":"2023-11-20T14:11:07Z","timestamp":1700489467000},"score":1,"resource":{"primary":{"URL":"https:\/\/dmsjournal.biomedcentral.com\/articles\/10.1186\/s13098-023-01187-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,10,26]]},"references-count":20,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2023,12]]}},"alternative-id":["1187"],"URL":"https:\/\/doi.org\/10.1186\/s13098-023-01187-7","relation":{},"ISSN":["1758-5996"],"issn-type":[{"value":"1758-5996","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,10,26]]},"assertion":[{"value":"23 July 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 October 2023","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 October 2023","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 study was approved by the institutional review board of Hokkaido University Hospital (018\u20130440), and informed consent was obtained from all participants.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"Nomoto H, Sakuma I, Nakamura A, and Atsumi T have received honoraria for lectures and research funding from the organizations listed below. Nomoto H received research grants from Kowa Pharmaceutical Co., Ltd., and honoraria for lectures from Novo Nordisk Pharma and Sumitomo Pharma Co., Ltd. Sakuma I received research grants from Kowa Pharmaceutical Co., Ltd. Nakamura A has received research support from Mitsubishi Tanabe Pharma, Daiichi Sankyo, MSD, Novo Nordisk Pharma, Novartis Pharma, AstraZeneca, Life Scan Japan, and Taisho Pharmaceutical Co., Ltd. TA received research grants from Astellas Pharma Inc., Takeda Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Co., Chugai Pharmaceutical Co., Ltd., Daiichi Sankyo Co., Ltd., Otsuka Pharmaceutical Co., Ltd., Pfizer Inc., Alexion Inc., Ono Pharmaceutical Co., Ltd., and Teijin Pharma Ltd.; speaking fees from Mitsubishi Tanabe Pharma Co., Chugai Pharmaceutical Co., Ltd., Astellas Pharma Inc., Takeda Pharmaceutical Co., Ltd., Pfizer Inc., AbbVie Inc., Eisai Co., Ltd., Daiichi Sankyo Co., Ltd., Bristol-Myers Squibb Co., UCB Japan Co., Ltd., Eli Lilly Japan K.K., Novartis Pharma K.K., Eli Lilly Japan K.K., Kyowa Kirin Co., Ltd., and Taisho Pharmaceutical Co., Ltd; and fees for consultancies from AstraZeneca plc., Medical & Biological Laboratories Co., Ltd., Pfizer Inc., AbbVie Inc., Ono Pharmaceutical Co., Ltd., Novartis Pharma K.K., and Nippon Boehringer Ingelheim Co., Ltd. The other authors declare no conflict of interest.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"214"}}