{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,16]],"date-time":"2025-12-16T11:53:36Z","timestamp":1765886016966,"version":"build-2065373602"},"reference-count":30,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2016,4,21]],"date-time":"2016-04-21T00:00:00Z","timestamp":1461196800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diabetes Obesity Metabolism"],"published-print":{"date-parts":[[2016,7]]},"abstract":"\n Aims<\/jats:title>\n \n To investigate the pharmacodynamics, pharmacokinetics and safety\/tolerability of blocking reuptake of bile acids using the inhibitor\n GSK2330672<\/jats:styled-content>\n (\n GSK672<\/jats:styled-content>\n ) in patients with type 2 diabetes (\n T2D<\/jats:styled-content>\n ).\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n Subjects with\n T2D<\/jats:styled-content>\n taking metformin were enrolled in two studies in which they took metformin 850\u2009mg twice daily for 2\u2009weeks prior to and during the randomized treatment periods. In the first crossover study (n\u2009=\u200915), subjects received\n GSK672<\/jats:styled-content>\n 45\u2009mg, escalating to 90\u2009mg, twice daily, or placebo for 7\u2009days. The second parallel\u2010group study (n\u2009=\u200975) investigated\n GSK672<\/jats:styled-content>\n 10\u201390\u2009mg twice daily, placebo or sitagliptin for 14\u2009days.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n In both studies,\n GSK672<\/jats:styled-content>\n reduced circulating bile acids and increased serum 7\u2010\u03b1\u2010hydroxy\u20104\u2010cholesten\u20103\u2010one (\n C4<\/jats:styled-content>\n ), an intermediate in the hepatic synthesis of bile acids. Compared with placebo, in the parallel\u2010group study 90\u2009mg\n GSK672<\/jats:styled-content>\n twice daily reduced fasting plasma glucose [\n FPG<\/jats:styled-content>\n ; \u22121.21\u2009mmol\/l; 95% confidence interval (\n CI<\/jats:styled-content>\n ) \u22122.14, \u22120.28] and weighted\u2010mean glucose area under the curve (\n AUC<\/jats:styled-content>\n )\n 0\u201324 h<\/jats:sub>\n (\u22121.33\u2009mmol\/l; 95%\n CI<\/jats:styled-content>\n \u22122.30, \u22120.36), as well as fasting and weighted\u2010mean insulin\n \n AUC\n 0<\/jats:sub>\n <\/jats:styled-content>\n \u201324 h<\/jats:sub>\n .\n GSK672<\/jats:styled-content>\n also reduced cholesterol (\n LDL<\/jats:styled-content>\n , non\u2010\n HDL<\/jats:styled-content>\n and total cholesterol) and apolipoprotein\n B<\/jats:styled-content>\n concentrations; the maximum\n LDL<\/jats:styled-content>\n cholesterol reduction was \u223c40%. There was no change in\n HDL<\/jats:styled-content>\n cholesterol but there was a trend towards increased fasting triglyceride levels in the\n GSK672<\/jats:styled-content>\n groups compared with placebo. In both studies, the most common adverse events associated with\n GSK672<\/jats:styled-content>\n were gastrointestinal, mostly diarrhoea (22\u2013100%), which appeared to be independent of dose.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n In subjects with\n T2D<\/jats:styled-content>\n on metformin,\n GSK672<\/jats:styled-content>\n improved glucose and lipids, but there was a high incidence of gastrointestinal adverse events.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/dom.12656","type":"journal-article","created":{"date-parts":[[2016,3,5]],"date-time":"2016-03-05T11:46:58Z","timestamp":1457178418000},"page":"654-662","source":"Crossref","is-referenced-by-count":30,"title":["Glucose and lipid effects of the ileal apical sodium\u2010dependent bile acid transporter inhibitor\n GSK2330672<\/scp>\n : double\u2010blind randomized trials with type 2 diabetes subjects taking metformin"],"prefix":"10.1111","volume":"18","author":[{"given":"D. J.","family":"Nunez","sequence":"first","affiliation":[{"name":"GlaxoSmithKline plc Research Triangle Park NC and Collegeville, PA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"X.","family":"Yao","sequence":"additional","affiliation":[{"name":"Alexion Pharmaceuticals, Inc. Cambridge MA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J.","family":"Lin","sequence":"additional","affiliation":[{"name":"Grifols Therapeutics Inc. Research Triangle Park NC USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A.","family":"Walker","sequence":"additional","affiliation":[{"name":"GlaxoSmithKline plc Research Triangle Park NC and Collegeville, PA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P.","family":"Zuo","sequence":"additional","affiliation":[{"name":"Parexel International Durham NC USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"L.","family":"Webster","sequence":"additional","affiliation":[{"name":"Nuventra, Inc. Durham NC USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S.","family":"Krug\u2010Gourley","sequence":"additional","affiliation":[{"name":"GlaxoSmithKline plc Research Triangle Park NC and Collegeville, PA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M. J.","family":"Zamek\u2010Gliszczynski","sequence":"additional","affiliation":[{"name":"GlaxoSmithKline plc Research Triangle Park NC and Collegeville, PA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D. S.","family":"Gillmor","sequence":"additional","affiliation":[{"name":"Pharmaceutical Product Development LLC Morrisville NC USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S. L.","family":"Johnson","sequence":"additional","affiliation":[{"name":"Pfizer Inc. 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