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As the mechanism of action of sodium\u2010glucose cotransporter\u00a02 inhibitors on plasma glucose levels is distinct from that of existing oral antidiabetic drugs, a combination of the two might provide a therapeutic benefit. Here, we investigated the antihyperglycemic effect of ipragliflozin, a selective sodium\u2010glucose cotransporter\u00a02 inhibitor, alone or in combination with oral antidiabetic drugs in a range of relevant mouse models to analyse the blood glucose\u2010lowering properties of different drug types based on their mechanism of action. Oral glucose tolerance tests in <jats:styled-content style=\"fixed-case\">ICR<\/jats:styled-content> mice were used to evaluate the effect of ipragliflozin in combination with the insulin secretagogues, glibenclamide or nateglinide. Liquid meal tests in <jats:styled-content style=\"fixed-case\">ICR<\/jats:styled-content> mice and diabetic <jats:styled-content style=\"fixed-case\">KK<\/jats:styled-content>\u2010A<jats:sup>y<\/jats:sup> mice were used to investigate the combined effect of ipragliflozin with the dipeptidyl peptidase\u20104 inhibitor, sitagliptin, and <jats:italic>\u03b1<\/jats:italic>\u2010glucosidase inhibitor, voglibose, respectively. Four\u2010week repeated administration tests in <jats:styled-content style=\"fixed-case\">KK<\/jats:styled-content>\u2010A<jats:sup>y<\/jats:sup> mice were used to examine the combined effect of ipragliflozin with the insulin sensitizers, pioglitazone and metformin. In all mouse models tested, the combination of ipragliflozin and existing oral antidiabetic drugs lowered blood glucose or glycated hemoglobin levels more than either monotherapy. In conclusion, inhibition of sodium\u2010glucose cotransporter\u00a02 by ipragliflozin, alone or in combination with existing oral antidiabetic drugs, has a robust effect on blood glucose levels in a range of mouse models of hyperglycemia.<\/jats:p>","DOI":"10.1111\/1440-1681.12317","type":"journal-article","created":{"date-parts":[[2014,10,14]],"date-time":"2014-10-14T06:49:18Z","timestamp":1413269358000},"page":"87-93","source":"Crossref","is-referenced-by-count":7,"title":["Antihyperglycemic effect of ipragliflozin, a sodium\u2010glucose co\u2010transporter\u00a02 inhibitor, in combination with oral antidiabetic drugs in mice"],"prefix":"10.1111","volume":"42","author":[{"given":"Toshiyuki","family":"Takasu","sequence":"first","affiliation":[{"name":"Tsukuba Research Center Drug Discovery Research Astellas Pharma Tsukuba Ibaraki Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuka","family":"Hayashizaki","sequence":"additional","affiliation":[{"name":"Tsukuba Research Center Drug Discovery Research Astellas Pharma Tsukuba Ibaraki Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Atsuo","family":"Tahara","sequence":"additional","affiliation":[{"name":"Tsukuba Research Center Drug Discovery Research Astellas Pharma Tsukuba Ibaraki Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eiji","family":"Kurosaki","sequence":"additional","affiliation":[{"name":"Tsukuba Research Center Drug Discovery Research Astellas Pharma Tsukuba Ibaraki Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shoji","family":"Takakura","sequence":"additional","affiliation":[{"name":"Tsukuba Research Center Drug Discovery Research Astellas Pharma Tsukuba Ibaraki Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2014,12,22]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/dmrr.981"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/0168-8227(95)01064-K"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(98)07019-6"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI7231"},{"key":"e_1_2_6_6_1","first-page":"1747","article-title":"Oral agents in the management of type 2 diabetes mellitus","volume":"63","author":"Luna B","year":"2001","journal-title":"Am. 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