{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T07:29:27Z","timestamp":1778657367498,"version":"3.51.4"},"reference-count":27,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2017,3,31]],"date-time":"2017-03-31T00:00:00Z","timestamp":1490918400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Takeda Development Center Americas, Deerfield","award":["IL 60015"],"award-info":[{"award-number":["IL 60015"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diabetes Obesity Metabolism"],"published-print":{"date-parts":[[2017,8]]},"abstract":"\n Aims<\/jats:title>\n \n To evaluate the efficacy and safety of fasiglifam, an orally active\n G<\/jats:styled-content>\n \u2010protein\u2010coupled receptor 40 agonist, in combination with the dipeptidyl peptidase\u20104 inhibitor sitagliptin, in patients with type 2 diabetes inadequately controlled with diet\/exercise (\u00b1 metformin).\n <\/jats:p>\n <\/jats:sec>\n \n Materials and methods<\/jats:title>\n \n In this randomized, double\u2010blind, phase\n II<\/jats:styled-content>\n study, 368 patients received once\u2010daily placebo, sitagliptin 100\u2009mg, fasiglifam 25 or 50\u2009mg, or the combination of sitagliptin 100\u2009mg plus fasiglifam 25 or 50\u2009mg. The primary endpoint was change from baseline glycated haemoglobin (\n HbA1c<\/jats:styled-content>\n ) at 12\u2009weeks; a key secondary endpoint was change in fasting plasma glucose (\n FPG<\/jats:styled-content>\n ).\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n The fasiglifam 25 and 50\u2009mg combination regimens produced significantly greater\n HbA1c<\/jats:styled-content>\n reductions than sitagliptin (treatment differences of \u22120.45% and \u22120.61%;\n \n P<\/jats:styled-content>\n <\/jats:italic>\n \u2009<\u2009.01, respectively) or respective doses of fasiglifam monotherapy (\u22120.43% and \u22120.48%;\n \n P<\/jats:styled-content>\n <\/jats:italic>\n \u2009<\u2009.01) and significantly greater\n FPG<\/jats:styled-content>\n reductions than sitagliptin (\u22121.1\u2009mmol\/\n L<\/jats:styled-content>\n for both combination regimens;\n \n P<\/jats:styled-content>\n <\/jats:italic>\n \u2009<\u2009.01). Improved glycaemic control occurred by week 1 for\n FPG<\/jats:styled-content>\n and week 4 for\n HbA1c<\/jats:styled-content>\n in all groups. Hypoglycaemia rates were low (\u22643.3%) and similar across treatments. Liver enzymes >3\u2009\u00d7\u2009upper limit of normal occurred in four patients (fasiglifam 25\u2009mg, n\u2009=\u20091; fasiglifam 50\u2009mg, n\u2009=\u20092; 1 fasiglifam\/sitagliptin 50\/100\u2009mg, n\u2009=\u20091).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n Combination of fasiglifam and sitagliptin provided significant additional effects on glycaemic control, with hypoglycaemia rates similar to placebo with or without metformin. This study provides supportive clinical evidence for the complementary mechanism of actions of this\n GPR40<\/jats:styled-content>\n agonist and\n DPP<\/jats:styled-content>\n \u20104 inhibitor.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/dom.12921","type":"journal-article","created":{"date-parts":[[2017,2,27]],"date-time":"2017-02-27T01:42:39Z","timestamp":1488159759000},"page":"1127-1134","source":"Crossref","is-referenced-by-count":11,"title":["Combining the\n G<\/scp>\n \u2010protein\u2010coupled receptor 40 agonist fasiglifam with sitagliptin improves glycaemic control in patients with type 2 diabetes with or without metformin:\n A<\/scp>\n randomized, 12\u2010week trial"],"prefix":"10.1111","volume":"19","author":[{"given":"Xuejun V.","family":"Peng","sequence":"first","affiliation":[{"name":"Takeda Development Center Americas, Inc. Deerfield Illinois"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9408-1889","authenticated-orcid":false,"given":"John F.","family":"Marcinak","sequence":"additional","affiliation":[{"name":"Takeda Development Center Americas, Inc. Deerfield Illinois"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marsha G.","family":"Raanan","sequence":"additional","affiliation":[{"name":"Takeda Development Center Americas, Inc. Deerfield Illinois"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Charlie","family":"Cao","sequence":"additional","affiliation":[{"name":"Takeda Development Center Americas, Inc. Deerfield Illinois"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2017,3,31]]},"reference":[{"key":"e_1_2_6_2_1","volume-title":"IDF Diabetes Atlas","author":"International Diabetes Federation","year":"2015"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa066224"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc14-2441"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.drudis.2013.09.003"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M211495200"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.111.187708"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.111.183772"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tem.2013.03.003"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.2012.43"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1463-1326.2011.01525.x"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(11)61879-5"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc12-0872"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1177\/0091270011409230"},{"key":"e_1_2_6_15_1","unstructured":"KakuK EnyaK NakayaR OohiraT MatsunoR. Efficacy and safety of fasiglifam (TAK\u2010875) a GPR40 selective agonist in Japanese type 2 diabetes mellitus patients: a phase 3 double\u2010blind placebo controlled comparative study [ePoster #888].49th Annual Meeting of the European Association for the Study of Diabetes;2013.Barcelona Spain."},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/dom.12693"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2006-1009"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00401145"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc06-0703"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc07-0627"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1742-1241.2010.02353.x"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1185\/03007990802705679"},{"key":"e_1_2_6_23_1","unstructured":"Takeda Press Release.Takeda announces termination of Fasiglifam (TAK\u2010875) development.2013.http:\/\/www.takeda.us\/newsroom\/press_release_detail.aspx?id=296. 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