{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T13:29:55Z","timestamp":1783430995741,"version":"3.54.6"},"reference-count":38,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2022,1,1]],"date-time":"2022-01-01T00:00:00Z","timestamp":1640995200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2022,1,1]],"date-time":"2022-01-01T00:00:00Z","timestamp":1640995200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2022,1,1]],"date-time":"2022-01-01T00:00:00Z","timestamp":1640995200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2022,1,1]],"date-time":"2022-01-01T00:00:00Z","timestamp":1640995200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2022,1,1]],"date-time":"2022-01-01T00:00:00Z","timestamp":1640995200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2022,1,1]],"date-time":"2022-01-01T00:00:00Z","timestamp":1640995200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2022,1,1]],"date-time":"2022-01-01T00:00:00Z","timestamp":1640995200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81430082"],"award-info":[{"award-number":["81430082"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012172","name":"Double First Class University Plan","doi-asserted-by":"publisher","award":["CPU2018GF08"],"award-info":[{"award-number":["CPU2018GF08"]}],"id":[{"id":"10.13039\/501100012172","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012246","name":"Priority Academic Program Development of Jiangsu Higher Education Institutions","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100012246","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["European Journal of Pharmacology"],"published-print":{"date-parts":[[2022,1]]},"DOI":"10.1016\/j.ejphar.2021.174635","type":"journal-article","created":{"date-parts":[[2021,11,17]],"date-time":"2021-11-17T11:24:04Z","timestamp":1637148244000},"page":"174635","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":13,"special_numbering":"C","title":["An oral GLP-1 and GIP dual receptor agonist improves metabolic disorders in high fat-fed mice"],"prefix":"10.1016","volume":"914","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3800-837X","authenticated-orcid":false,"given":"Teng","family":"Ma","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weisheng","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongkang","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Qian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Tian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangdong","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenbing","family":"Yao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.ejphar.2021.174635_bib1","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.ijpharm.2015.12.043","article-title":"Absorption-enhancing effects of gemini surfactant on the intestinal absorption of poorly absorbed hydrophilic drugs including peptide and protein drugs in rats","volume":"499","author":"Alama","year":"2016","journal-title":"Int. J. Pharm."},{"key":"10.1016\/j.ejphar.2021.174635_bib2","first-page":"CD010481","article-title":"Amphotericin B deoxycholate versus liposomal amphotericin B: effects on kidney function","volume":"11","author":"Juan Pablo Botero Aguirre","year":"2015","journal-title":"Cochrane Database Syst. Rev."},{"key":"10.1016\/j.ejphar.2021.174635_bib3","doi-asserted-by":"crossref","first-page":"4293","DOI":"10.1021\/acs.jmedchem.7b00174","article-title":"Design of novel exendin-based dual glucagon-like peptide 1 (GLP-1)\/Glucagon receptor agonists","volume":"60","author":"Andreas","year":"2017","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.ejphar.2021.174635_bib4","doi-asserted-by":"crossref","first-page":"5580","DOI":"10.1021\/acs.jmedchem.8b00292","article-title":"Dual glucagon-like peptide 1 (GLP-1)\/Glucagon receptor agonists specifically optimized for multidose formulations","volume":"61","author":"Andreas","year":"2018","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.ejphar.2021.174635_bib5","doi-asserted-by":"crossref","first-page":"170202","DOI":"10.1016\/j.peptides.2019.170202","article-title":"GIP analogues and the treatment of obesity-diabetes","volume":"25","author":"Bailey","year":"2020","journal-title":"Peptides"},{"key":"10.1016\/j.ejphar.2021.174635_bib6","first-page":"1","article-title":"Unimolecular dual incretins maximize metabolic benefits in rodents, monkeys, and humans","volume":"209","author":"Brian","year":"2013","journal-title":"Sci. Transl. Med."},{"key":"10.1016\/j.ejphar.2021.174635_bib7","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1038\/nm.3761","article-title":"A rationally designed monomeric peptide triagonist corrects obesity and diabetes in rodents","volume":"21","author":"Brian","year":"2015","journal-title":"Nat. Med."},{"key":"10.1016\/j.ejphar.2021.174635_bib8","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1016\/j.molmed.2016.03.005","article-title":"Reappraisal of GIP pharmacology for metabolic diseases","volume":"22","author":"Brian","year":"2016","journal-title":"Trends Mol. Med."},{"key":"10.1016\/j.ejphar.2021.174635_bib9","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1016\/j.ijpharm.2017.03.020","article-title":"The absorption enhancer sodium deoxycholate promotes high gene transfer in skeletal muscles","volume":"523","author":"Christian","year":"2017","journal-title":"Int. J. Pharm."},{"key":"10.1016\/j.ejphar.2021.174635_bib10","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1038\/s41574-018-0118-x","article-title":"Emerging hormonal-based combination pharmacotherapies for the treatment of metabolic diseases","volume":"15","author":"Clemmensen","year":"2019","journal-title":"Nat. Rev. Endocrinol."},{"key":"10.1016\/j.ejphar.2021.174635_bib11","doi-asserted-by":"crossref","first-page":"113723","DOI":"10.1016\/j.bcp.2019.113723","article-title":"A GIP\/xenin hybrid in combination with exendin-4 improves metabolic status in db\/db diabetic mice and promotes enduring antidiabetic benefits in high fat fed mice","volume":"171","author":"Craig","year":"2020","journal-title":"Biochem. Pharmacol."},{"key":"10.1016\/j.ejphar.2021.174635_bib12","doi-asserted-by":"crossref","first-page":"2332","DOI":"10.2337\/db13-1563","article-title":"Chronic reduction of GIP secretion alleviates obesity and insulin resistance under high-fat diet conditions","volume":"63","author":"Daniela","year":"2014","journal-title":"Diabetes"},{"key":"10.1016\/j.ejphar.2021.174635_bib13","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1111\/j.1365-2125.2009.03549.x","article-title":"Regulatory challenges for new drugs to treat obesity and comorbid metabolic disorders","volume":"68","author":"David","year":"2009","journal-title":"Br. J. Clin. Pharmacol."},{"key":"10.1016\/j.ejphar.2021.174635_bib14","article-title":"Anti-obesity effects of GIPR antagonists alone and in combination with GLP-1R agonists in preclinical models","volume":"10","author":"Elizabeth","year":"2018","journal-title":"Sci. Transl. Med."},{"key":"10.1016\/j.ejphar.2021.174635_bib15","doi-asserted-by":"crossref","first-page":"1724","DOI":"10.1007\/s00125-009-1422-8","article-title":"Evidence for beneficial effects of compromised gastric inhibitory polypeptide action in obesity-related diabetes and possible therapeutic implications","volume":"52","author":"Irwin","year":"2009","journal-title":"Diabetologia"},{"key":"10.1016\/j.ejphar.2021.174635_bib16","doi-asserted-by":"crossref","first-page":"1187","DOI":"10.1007\/s40265-019-01153-6","article-title":"Designing poly-agonists for treatment of metabolic diseases: challenges and opportunities","volume":"79","author":"Jonas","year":"2019","journal-title":"Drugs"},{"key":"10.1016\/j.ejphar.2021.174635_bib17","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1016\/j.cmet.2017.07.011","article-title":"The sustained effects of a dual GIP\/GLP-1 receptor agonist, NNC0090-2746, in patients with type 2 diabetes","volume":"26","author":"Juan","year":"2017","journal-title":"Cell Metabol."},{"key":"10.1016\/j.ejphar.2021.174635_bib18","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1016\/j.diabres.2012.04.013","article-title":"Increase of INS-1 cell apoptosis under glucose fluctuation and the involvement of FOXO\u2013SIRT pathway","volume":"98","author":"Kim","year":"2012","journal-title":"Diabetes Res. Clin. Pract."},{"key":"10.1016\/j.ejphar.2021.174635_bib19","series-title":"Animal Models of Type 1 and Type 2 Diabetes Mellitus in Animal Models for the Study of Human Disease","first-page":"245","author":"King","year":"2017"},{"key":"10.1016\/j.ejphar.2021.174635_bib20","article-title":"Cracking the combination: gut hormones for the treatment of obesity and diabetes","volume":"31","author":"Kleopatra","year":"2019","journal-title":"J. Neuroendocrinol."},{"key":"10.1016\/j.ejphar.2021.174635_bib21","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/0169-409X(89)90018-5","article-title":"Penetration and enzymatic barriers to peptide and protein absorption","volume":"4","year":"1989","journal-title":"Adv. Drug Deliv. Rev."},{"key":"10.1016\/j.ejphar.2021.174635_bib22","doi-asserted-by":"crossref","first-page":"18365","DOI":"10.1074\/jbc.M710466200","article-title":"Targeted ablation of glucose-dependent insulinotropic polypeptide-producing cells in transgenic mice reduces obesity and insulin resistance induced by a high fat diet","volume":"283","author":"Matthew","year":"2008","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.ejphar.2021.174635_bib23","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1172\/JCI116186","article-title":"Preserved incretin activity of glucagon-like peptide 1[7-36 amide] but not of synthetic human gastric inhibitory polypeptide in patients with type-2 diabetes mellitus","volume":"91","author":"Michael","year":"1993","journal-title":"J. Clin. Invest."},{"key":"10.1016\/j.ejphar.2021.174635_bib24","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/j.regpep.2004.08.021","article-title":"Overexpression of a dominant negative GIP receptor in transgenic mice results in disturbed postnatal pancreatic islet and beta-cell development","volume":"125","author":"Nadja","year":"2005","journal-title":"Regul. Pept."},{"key":"10.1016\/j.ejphar.2021.174635_bib25","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1016\/j.bcp.2018.07.021","article-title":"Novel dual incretin agonist peptide with antidiabetic and neuroprotective potential","volume":"155","author":"Pathak","year":"2018","journal-title":"Biochem. Pharmacol."},{"key":"10.1016\/j.ejphar.2021.174635_bib26","doi-asserted-by":"crossref","first-page":"2607","DOI":"10.1016\/S0140-6736(18)30726-8","article-title":"MEDI0382, a GLP-1 and glucagon receptor dual agonist, in obese or overweight patients with type 2 diabetes: a randomised, controlled, double-blind, ascending dose and phase 2a study","volume":"391","author":"Philip","year":"2018","journal-title":"Lancet"},{"key":"10.1016\/j.ejphar.2021.174635_bib27","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.molmet.2018.12.001","article-title":"Optimized GIP analogs promote body weight lowering in mice through GIPR agonism not antagonism","volume":"20","author":"Piotr","year":"2019","journal-title":"Molecular Metabolism"},{"key":"10.1016\/j.ejphar.2021.174635_bib28","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.bbrc.2008.08.052","article-title":"Inhibition of GIP signaling modulates adiponectin levels under high-fat diet in mice","volume":"376","author":"Rei","year":"2008","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"10.1016\/j.ejphar.2021.174635_bib29","first-page":"411","article-title":"How may GIP enhance the therapeutic efficacy of GLP-1","volume":"31","author":"Ricardo","year":"2020","journal-title":"Trends Endocrinol. Metabol."},{"key":"10.1016\/j.ejphar.2021.174635_bib30","doi-asserted-by":"crossref","first-page":"578","DOI":"10.3390\/ijms18030578","article-title":"Systematic design of trypsin cleavage site mutated exendin4-cysteine 1, an orally bioavailable glucagon-like peptide-1 receptor agonist","volume":"18","author":"Sai","year":"2017","journal-title":"Int. J. Mol. Sci."},{"key":"10.1016\/j.ejphar.2021.174635_bib31","doi-asserted-by":"crossref","first-page":"1657","DOI":"10.1007\/s00266-019-01514-2","article-title":"Effect of a formulation containing low-dose sodium deoxycholate on local fat reduction","volume":"43","author":"Sang","year":"2019","journal-title":"Aesthetic Plast. Surg."},{"key":"10.1016\/j.ejphar.2021.174635_bib32","article-title":"A GIP receptor agonist exhibits beta-cell anti-apoptotic actions in rat models of diabetes resulting in improved beta-cell function and glycemic control","volume":"5","author":"Scott","year":"2010","journal-title":"PLoS One"},{"key":"10.1016\/j.ejphar.2021.174635_bib33","doi-asserted-by":"crossref","first-page":"1431","DOI":"10.1185\/03007995.2011.585396","article-title":"Impact of weight gain on outcomes in type 2 diabetes","volume":"27","author":"Stuart","year":"2011","journal-title":"Curr. Med. Res. Opin."},{"key":"10.1016\/j.ejphar.2021.174635_bib34","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.molmet.2018.09.009","article-title":"LY3298176, a novel dual GIP and GLP-1 receptor agonist for the treatment of type 2 diabetes mellitus: from discovery to clinical proof of concept","volume":"18","author":"Tamer","year":"2018","journal-title":"Molecular Metabolism"},{"key":"10.1016\/j.ejphar.2021.174635_bib35","doi-asserted-by":"crossref","first-page":"4897","DOI":"10.1210\/jc.2003-030738","article-title":"The pathophysiology of diabetes involves a defective amplification of the late-phase insulin response to glucose by glucose-dependent insulinotropic polypeptide\u2014regardless of etiology and phenotype","volume":"88","author":"Vilsboll","year":"2003","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"10.1016\/j.ejphar.2021.174635_bib36","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/S0022-3565(25)10333-9","article-title":"A mechanistic study on enhancement of rectal permeability to insulin in the albino rabbit","volume":"263","author":"Yamamoto","year":"1992","journal-title":"J. Pharmacol. Exp. Therapeut."},{"issue":"12","key":"10.1016\/j.ejphar.2021.174635_bib37","doi-asserted-by":"crossref","first-page":"1285","DOI":"10.1111\/j.2042-7158.1996.tb03937.x","article-title":"Effectiveness and toxicity screening of various absorption enhancers in the rat small intestine: effects of absorption enhancers on the intestinal absorption of phenol red and the release of protein and phospholipids from the intestinal membrane","volume":"48","author":"Yamamoto","year":"1996","journal-title":"J. Pharm. Pharmacol."},{"key":"10.1016\/j.ejphar.2021.174635_bib38","doi-asserted-by":"crossref","first-page":"107537","DOI":"10.1016\/j.pharmthera.2020.107537","article-title":"Approaches to improve intestinal and transmucosal absorption of peptide and protein drugs","volume":"211","author":"Yamamoto","year":"2020","journal-title":"Pharmacol. Ther."}],"container-title":["European Journal of Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0014299921007913?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0014299921007913?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,9,15]],"date-time":"2025-09-15T22:59:24Z","timestamp":1757977164000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0014299921007913"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,1]]},"references-count":38,"alternative-id":["S0014299921007913"],"URL":"https:\/\/doi.org\/10.1016\/j.ejphar.2021.174635","relation":{},"ISSN":["0014-2999"],"issn-type":[{"value":"0014-2999","type":"print"}],"subject":[],"published":{"date-parts":[[2022,1]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"An oral GLP-1 and GIP dual receptor agonist improves metabolic disorders in high fat-fed mice","name":"articletitle","label":"Article Title"},{"value":"European Journal of Pharmacology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ejphar.2021.174635","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2021 Elsevier B.V. All rights reserved.","name":"copyright","label":"Copyright"}],"article-number":"174635"}}