{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T15:27:29Z","timestamp":1773329249021,"version":"3.50.1"},"reference-count":58,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,8,22]],"date-time":"2022-08-22T00:00:00Z","timestamp":1661126400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec><jats:title>Purpose<\/jats:title><jats:p>Dipeptidyl peptidase-4 inhibitors (DPP-4I), key regulators of the actions of incretin hormones, exert anti-hyperglycemic effects in type 2 diabetes mellitus (T2DM) patients. A major unanswered question concerns the potential ability of DPP-4I to improve intrahepatic lipid (IHL) content in nonalcoholic fatty liver disease (NAFLD) patients. The aim of this study was to evaluate the effects of sitagliptin on IHL in NAFLD patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A prospective, 24-week, single-center, open-label, comparative study enrolled 68 Chinese NAFLD patients with T2DM. Subjects were randomly divided into 4 groups: control group who did not take medicine (14 patients); sitagliptin group who received sitagliptin treatment (100mg per day) (17 patients); metformin group who received metformin (500mg three times per day) (17 patients); and sitagliptin plus metformin group who received sitagliptin (100mg per day) and metformin (500 mg three times per day) (20 patients). IHL, physical examination (waist circumstances, WC; body mass index, BMI), glucose-lipid metabolism (fasting plasma glucose, FPG; hemoglobin A1c, Hb1A1c; triglycerides; cholesterol; alanine aminotransferase, ALT; aspartate aminotransferase, AST) were measured at baseline and at 24 weeks.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>1) WC and BMI were decreased significantly in all groups except control group (all <jats:italic>P&amp;lt;<\/jats:italic>0.05). 2) There was no statistically significant difference in IHL among the sitagliptin, metformin, and sitagliptin plus metformin groups before and after treatment(all <jats:italic>P<\/jats:italic>&amp;gt;0.05). Only the metformin group showed a statistically significant difference in IHL before and after treatment(<jats:italic>P<\/jats:italic>&amp;lt;0.05). 3) Sitagliptin treatment led to a significant decrease in FBG and HbA1c when compared with the control group (all <jats:italic>P&amp;lt;<\/jats:italic>0.01). Additionally, HhA1c was significant decreased in the sitagliptin group when compared with the metformin group (<jats:italic>P<\/jats:italic>&amp;lt; 0.05). 4) HbA1c and FBG were decreased by 0.8% and 0.7 mmol\/l respectively and the percentage of patients with HbA1c less than 7% was 65% with sitagliptin treatment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Sitagliptin improves abnormalities in glucose metabolism, but not reduces the IHL in T2DM with NAFLD, indicating that sitagliptin might be a therapeutic option for treatment of NAFLD indirectly while not directly on IHL. Clinical Trial Registration: <jats:uri>https:\/\/clinicaltrials.gov\/<\/jats:uri>, identifier CTR# NCT05480007.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fendo.2022.866189","type":"journal-article","created":{"date-parts":[[2022,8,22]],"date-time":"2022-08-22T05:05:58Z","timestamp":1661144758000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":20,"title":["Effects of sitagliptin on intrahepatic lipid content in patients with non-alcoholic fatty liver disease"],"prefix":"10.3389","volume":"13","author":[{"given":"Xingchun","family":"Wang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bangfeng","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hang","family":"Sun","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hui","family":"You","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shen","family":"Qu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2022,8,22]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/j.dld.2010.01.016","article-title":"From the metabolic syndrome to NAFLD or vice versa","volume":"42","author":"Vanni","year":"2010","journal-title":"Digestive liver Dis Off J Ital Soc Gastroenterol Ital Assoc Study Liver"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1053\/gast.2002.36572","article-title":"AGA technical review on nonalcoholic fatty liver disease","volume":"123","author":"Sanyal","year":"2002","journal-title":"Gastroenterology"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/s0002-9343(99)00271-5","article-title":"Association of nonalcoholic fatty liver disease with insulin resistance","volume":"107","author":"Marchesini","year":"1999","journal-title":"Am J Med"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra011775","article-title":"Nonalcoholic fatty liver disease","author":"Angulo","year":"2005","journal-title":"Rev gastroenterologia Mexico"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v13.i26.3540","article-title":"Metabolic liver disease of obesity and role of adipose tissue in the pathogenesis of nonalcoholic fatty liver disease","volume":"13","author":"Qureshi","year":"2007","journal-title":"World J Gastroenterol WJG"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2007-0482","article-title":"Liver fat in the metabolic syndrome","volume":"92","author":"Kotronen","year":"2007","journal-title":"J Clin Endocrinol Metab"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1080\/07853890510037383","article-title":"Fat in the liver and insulin resistance","volume":"37","author":"Yki-Jarvinen","year":"2005","journal-title":"Ann Med"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.2337\/dc10-0856","article-title":"Effect of a 12-month intensive lifestyle intervention on hepatic steatosis in adults with type 2 diabetes","volume":"33","author":"Lazo","year":"2010","journal-title":"Diabetes Care"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1055\/s-0028-1091986","article-title":"Effects of weight loss on nonalcoholic fatty liver disease","volume":"28","author":"Rafiq","year":"2008","journal-title":"Semin Liver Disease"},{"key":"B10","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1111\/j.1365-2036.2004.01888.x","article-title":"Therapy of nonalcoholic fatty liver disease: Current status","author":"Duvnjak","year":"2009","journal-title":"J Physiol Pharmacol an Off J Polish Physiol Society"},{"key":"B11","doi-asserted-by":"crossref","DOI":"10.1111\/j.1365-2036.2004.01888.x","article-title":"Metformin in the treatment of patients with non-alcoholic steatohepatitis","volume":"19","author":"Uygun","year":"2004","journal-title":"Alimentary Pharmacol Ther"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1038\/nrgastro.2010.50","article-title":"NASH: Thiazolidinediones for NASH\u2013one pill doesn't fix everything","volume":"7","author":"Neuschwander-Tetri","year":"2010","journal-title":"Nat Rev Gastroenterol Hepatol"},{"key":"B13","doi-asserted-by":"publisher","first-page":"998","DOI":"10.1038\/79697","article-title":"Metformin reverses fatty liver disease in obese, leptin-deficient mice","volume":"6","author":"Lin","year":"2000","journal-title":"Nat Med"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ijo.0802625","article-title":"Plasma resistin concentration, hepatic fat content, and hepatic and peripheral insulin resistance in pioglitazone-treated type II diabetic patients","volume":"28","author":"Bajaj","year":"2004","journal-title":"Int J Obes related Metab Disord J Int Assoc Study Obes"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1111\/j.1572-0241.2001.03553.x","article-title":"A pilot study of a thiazolidinedione, troglitazone, in nonalcoholic steatohepatitis","volume":"96","author":"Caldwell","year":"2001","journal-title":"Am J Gastroenterology"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1016\/s0167-0115(03)00111-3","article-title":"Both GLP-1 and GIP are insulinotropic at basal and postprandial glucose levels and contribute nearly equally to the incretin effect of a meal in healthy subjects","volume":"114","author":"Vilsboll","year":"2003","journal-title":"Regul Peptides"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2003-031907","article-title":"Inhibition of dipeptidyl peptidase-4 reduces glycemia, sustains insulin levels, and reduces glucagon levels in type 2 diabetes","volume":"89","author":"Ahren","year":"2004","journal-title":"J Clin Endocrinol Metab"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1016\/j.regpep.2004.07.019","article-title":"GIP and GLP-1 as incretin hormones: lessons from single and double incretin receptor knockout mice","volume":"128","author":"Hansotia","year":"2005","journal-title":"Regul Peptides"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1210\/en.2004-1174","article-title":"Inhibition of dipeptidyl peptidase-4 augments insulin secretion in response to exogenously administered glucagon-like peptide-1, glucose-dependent insulinotropic polypeptide, pituitary adenylate cyclase-activating polypeptide, and gastrin-releasing peptide in mice","volume":"146","author":"Ahren","year":"2005","journal-title":"Endocrinology"},{"key":"B20","article-title":"[Exendin-4 protected murine MIN6 pancreatic beta-cells from oxidative stress-induced apoptosis via down-regulation of NF-kappaB-iNOS-NO pathway]","volume":"43","author":"Liu","year":"2008","journal-title":"Yao xue xue bao = Acta Pharm Sinica"},{"key":"B21","doi-asserted-by":"publisher","first-page":"194","DOI":"10.1001\/jama.298.2.194","article-title":"Efficacy and safety of incretin therapy in type 2 diabetes: systematic review and meta-analysis","volume":"298","author":"Amori","year":"2007","journal-title":"JAMA"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1592\/phco.30.5.463","article-title":"Dipeptidyl peptidase-4 inhibitors for the treatment of type 2 diabetes mellitus","volume":"30","author":"Neumiller","year":"2010","journal-title":"Pharmacotherapy"},{"key":"B23","doi-asserted-by":"publisher","first-page":"696","DOI":"10.1007\/s00125-012-2827-3","article-title":"Differences in the glucose-lowering efficacy of dipeptidyl peptidase-4 inhibitors between asians and non-asians: a systematic review and meta-analysis","volume":"56","author":"Kim","year":"2013","journal-title":"Diabetologia"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1016\/j.diabres.2008.10.009","article-title":"Efficacy and safety of sitagliptin in the treatment of patients with type 2 diabetes in China, India, and Korea","volume":"83","author":"Mohan","year":"2009","journal-title":"Diabetes Res Clin Practice"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1097\/MAJ.0b013e31818eb721","article-title":"Impact of sitagliptin on markers of beta-cell function: a meta-analysis","volume":"337","author":"Riche","year":"2009","journal-title":"Am J Med Sci"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1111\/j.1742-1241.2010.02353.x","article-title":"Safety and efficacy of treatment with sitagliptin or glipizide in patients with type 2 diabetes inadequately controlled on metformin: A 2-year study","volume":"64","author":"Seck","year":"2010","journal-title":"Int J Clin Practice"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1002\/hep.23569","article-title":"Glucagon-like peptide-1 receptor is present on human hepatocytes and has a direct role in decreasing hepatic steatosis in vitro by modulating elements of the insulin signaling pathway","volume":"51","author":"Gupta","year":"2010","journal-title":"Hepatol (Baltimore Md)"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.5754\/hge11689","article-title":"Non-alcoholic fatty liver disease adversely affects the glycemic control afforded by sitagliptin","volume":"59","author":"Iwasaki","year":"2012","journal-title":"Hepato-gastroenterology"},{"key":"B29","article-title":"Efficacy and safety of sitagliptin for the treatment of nonalcoholic fatty liver disease with type 2 diabetes mellitus","volume":"61","author":"Fukuhara","year":"2014","journal-title":"Hepato-gastroenterology"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1111\/hepr.12077","article-title":"Efficacy and safety in sitagliptin therapy for diabetes complicated by non-alcoholic fatty liver disease","volume":"43","author":"Arase","year":"2013","journal-title":"Hepatol Res Off J Japan Soc Hepatol"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.5754\/hge11263","article-title":"Sitagliptin as a novel treatment agent for non-alcoholic fatty liver disease patients with type 2 diabetes mellitus","volume":"58","author":"Iwasaki","year":"2011","journal-title":"Hepato-gastroenterology"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1100\/2012\/496453","article-title":"The effectiveness of liraglutide in nonalcoholic fatty liver disease patients with type 2 diabetes mellitus compared to sitagliptin and pioglitazone","volume":"2012","author":"Ohki","year":"2012","journal-title":"Sci World J"},{"key":"B33","doi-asserted-by":"publisher","first-page":"e38744","DOI":"10.1371\/journal.pone.0038744","article-title":"Linagliptin improves insulin sensitivity and hepatic steatosis in diet-induced obesity","volume":"7","author":"Kern","year":"2012","journal-title":"PloS One"},{"key":"B34","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1016\/j.diabres.2014.04.028","article-title":"Sitagliptin attenuates methionine\/choline-deficient diet-induced steatohepatitis","volume":"105","author":"Jung","year":"2014","journal-title":"Diabetes Res Clin practice"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1016\/j.pcd.2010.02.004","article-title":"Non-alcoholic fatty liver disease (NAFLD): new challenge for general practitioners and important burden for health authorities","volume":"4","author":"Ahmed","year":"2010","journal-title":"Primary Care Diabetes"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000131515.03336.f8","article-title":"Role of endothelial dysfunction in atherosclerosis","volume":"109","author":"Davignon","year":"2004","journal-title":"Circulation"},{"key":"B37","doi-asserted-by":"publisher","first-page":"18l","DOI":"10.1016\/s0002-9149(02)02957-0","article-title":"Intima-media thickness: a tool for atherosclerosis imaging and event prediction","volume":"90","author":"O'Leary","year":"2002","journal-title":"Am J Cardiol"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2008.07.024","article-title":"The severity of nonalcoholic fatty liver disease is associated with increased cardiovascular risk in a large cohort of non-obese Asian subjects","volume":"203","author":"Sung","year":"2009","journal-title":"Atherosclerosis"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2009.01.048","article-title":"Dietary fat and carbohydrates differentially alter insulin sensitivity during caloric restriction","volume":"136","author":"Kirk","year":"2009","journal-title":"Gastroenterology"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2004-1959","article-title":"Effects of diet and exercise on muscle and liver intracellular lipid contents and insulin sensitivity in type 2 diabetic patients","volume":"90","author":"Tamura","year":"2005","journal-title":"J Clin Endocrinol Metab"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2006-2384","article-title":"Effects of diet-induced moderate weight reduction on intrahepatic and intramyocellular triglycerides and glucose metabolism in obese subjects","volume":"92","author":"Sato","year":"2007","journal-title":"J Clin Endocrinol Metab"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1016\/j.orcp.2010.12.007","article-title":"Intrahepatic lipid content is linked to insulin resistance in obese subjects","volume":"5","author":"Sada","year":"2011","journal-title":"Obes Res Clin practice"},{"key":"B43","article-title":"Effect of voxel position on single-voxel MR spectroscopy findings","volume":"21","author":"Ricci","year":"2000","journal-title":"AJNR Am J Neuroradiology"},{"key":"B44","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1148\/radiology.153.1.6089264","article-title":"Fatty infiltration of the liver: demonstration by proton spectroscopic imaging","volume":"153","author":"Lee","year":"1984","journal-title":"Preliminary Observations Radiology"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1126\/science.1167571","article-title":"Cell signaling","volume":"322","author":"Ogawa","year":"2008","journal-title":"Fat Stress Liver Resistance Sci (New York NY)"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1016\/j.plipres.2010.05.003","article-title":"Biosynthesis and bioavailability of long-chain polyunsaturated fatty acids in non-alcoholic fatty liver disease","volume":"49","author":"Gormaz","year":"2010","journal-title":"Prog Lipid Res"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1016\/j.numecd.2010.05.003","article-title":"Relationship between fatty liver and glucose metabolism: a cross-sectional study in 571 obese children","volume":"22","author":"Bedogni","year":"2012","journal-title":"Nutrition metabolism Cardiovasc Dis NMCD"},{"key":"B48","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1126\/science.7678183","article-title":"Adipose expression of tumor necrosis factor-alpha: direct role in obesity-linked insulin resistance","volume":"259","author":"Hotamisligil","year":"1993","journal-title":"Sci (New York NY)"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1016\/j.diabres.2007.07.012","article-title":"Probable NAFLD, by ALT levels, and diabetes among Filipino-American women","volume":"79","author":"Wong","year":"2008","journal-title":"Diabetes Res Clin practice"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1111\/j.1463-1326.2007.00801.x","article-title":"Effects of metformin on peripheral insulin sensitivity and intracellular lipid contents in muscle and liver of overweight Japanese subjects","volume":"10","author":"Tamura","year":"2008","journal-title":"Diabetes Obes Metab"},{"key":"B51","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1002\/hep.23623","article-title":"A meta-analysis of randomized trials for the treatment of nonalcoholic fatty liver disease","volume":"52","author":"Musso","year":"2010","journal-title":"Hepatol (Baltimore Md)"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1007\/s00592-011-0322-9","article-title":"Miglitol administered before breakfast increased plasma active glucagon-like peptide-1 (GLP-1) levels after lunch in patients with type 2 diabetes treated with sitagliptin","volume":"49","author":"Aoki","year":"2012","journal-title":"Acta Diabetologica"},{"key":"B53","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1007\/s00125-001-0719-z","article-title":"The pharmacokinetics, pharmacodynamics, safety and tolerability of NN2211, a new long-acting GLP-1 derivative, in healthy men","volume":"45","author":"Agerso","year":"2002","journal-title":"Diabetologia"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-011-2311-5","article-title":"Metformin activates AMP-activated protein kinase in primary human hepatocytes by decreasing cellular energy status","volume":"54","author":"Stephenne","year":"2011","journal-title":"Diabetologia"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2010.09.032","article-title":"Glucagon-like peptide-1 reduces hepatic lipogenesis via activation of AMP-activated protein kinase","volume":"54","author":"Ben-Shlomo","year":"2011","journal-title":"J hepatol"},{"key":"B56","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1016\/j.autneu.2003.11.001","article-title":"Receptor gene expression of glucagon-like peptide-1, but not glucose-dependent insulinotropic polypeptide, in rat nodose ganglion cells","volume":"110","author":"Nakagawa","year":"2004","journal-title":"Autonomic Neurosci Basic Clinical"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.50.11.2530","article-title":"Systemic administration of the long-acting GLP-1 derivative NN2211 induces lasting and reversible weight loss in both normal and obese rats","volume":"50","author":"Larsen","year":"2001","journal-title":"Diabetes"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0631828100","article-title":"Mice lacking dipeptidyl peptidase IV are protected against obesity and insulin resistance","volume":"100","author":"Conarello","year":"2003","journal-title":"Proc Natl Acad Sci USA"}],"container-title":["Frontiers in Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2022.866189\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,8,22]],"date-time":"2022-08-22T05:06:02Z","timestamp":1661144762000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2022.866189\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,8,22]]},"references-count":58,"alternative-id":["10.3389\/fendo.2022.866189"],"URL":"https:\/\/doi.org\/10.3389\/fendo.2022.866189","relation":{},"ISSN":["1664-2392"],"issn-type":[{"value":"1664-2392","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,8,22]]},"article-number":"866189"}}