{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,30]],"date-time":"2026-05-30T01:40:14Z","timestamp":1780105214317,"version":"3.54.0"},"reference-count":33,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2022,12,22]],"date-time":"2022-12-22T00:00:00Z","timestamp":1671667200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100001003","name":"Boehringer Ingelheim","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100001003","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["dom-pubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Diabetes Obesity Metabolism"],"published-print":{"date-parts":[[2023,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>To study the oral 11 beta\u2010hydroxysteroid dehydrogenase\u20101 (11\u03b2\u2010HSD1) inhibitor BI 187004 (NCT02150824), as monotherapy and in combination with metformin, versus placebo in patients with type 2 diabetes mellitus (T2DM) affected by overweight or obesity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods<\/jats:title>\n                    <jats:p>\n                      This Phase II, randomized controlled trial investigated multiple rising doses of BI 187004 as monotherapy (Arm 1: 20, 80 or 240\u2009mg) and in combination with metformin (Arm 2: 240\u2009mg), in adults with T2DM and a body mass index of 28\u201340\u2009kg\/m\n                      <jats:sup>2<\/jats:sup>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      In total, 103 patients (Arm 1: n\u00a0=\u00a062, Arm 2: n\u00a0=\u00a041) were included in this study. BI 187004 was rapidly absorbed and exposure increased approximately dose\u2010dependently. Target engagement of 11\u03b2\u2010HSD1 was observed with near\u2010full inhibition of 11\u03b2\u2010HSD1 in the liver [decreased (5\u03b1\u2010tetrahydrocortisol\u2009+\u20095\u03b2\u2010tetrahydrocortisol)\/tetrahydrocortisone ratio]; hypothalamic\u2013pituitary\u2013adrenal axis activation was also seen (increased total urinary corticosteroids). No clinically relevant changes from baseline with BI 187004 treatment were observed for bodyweight or meal tolerance test parameters, or in most efficacy endpoints testing glucose and lipid metabolism; a significant increase was observed in weighted mean plasma glucose (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u2009.05 for 80 and 240\u2009mg BI 187004) but not fasting plasma glucose. Drug\u2010related adverse events were reported for 14 patients (22.6%) in Arm 1 and 10 patients (24.4%) in Arm 2, most frequently headache, diarrhoea, flushing and dizziness. A dose\u2010dependent increase in heart rate was seen with BI 187004 treatment.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>BI 187004 was generally well tolerated in patients with T2DM. Despite complete 11\u03b2\u2010HSD1 inhibition, no clinically relevant effects were observed with BI 187004.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/dom.14932","type":"journal-article","created":{"date-parts":[[2022,12,7]],"date-time":"2022-12-07T10:53:31Z","timestamp":1670410411000},"page":"832-843","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Safety, tolerability, pharmacodynamics and pharmacokinetics following once\u2010daily doses of\n                    <scp>BI<\/scp>\n                    187004, an inhibitor of 11 beta\u2010hydroxysteroid dehydrogenase\u20101, over 28\u2009days in patients with type 2 diabetes mellitus and overweight or obesity"],"prefix":"10.1111","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1638-4286","authenticated-orcid":false,"given":"Susanna","family":"Bianzano","sequence":"first","affiliation":[{"name":"Boehringer Ingelheim International GmbH  Ingelheim Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1760-1550","authenticated-orcid":false,"given":"Matias","family":"Nordaby","sequence":"additional","affiliation":[{"name":"Boehringer Ingelheim International GmbH  Ingelheim Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1907-761X","authenticated-orcid":false,"given":"Leona","family":"Plum\u2010M\u00f6rschel","sequence":"additional","affiliation":[{"name":"Profil  Neuss Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Peil","sequence":"additional","affiliation":[{"name":"Boehringer Ingelheim Pharma GmbH &amp; Co. KG  Ingelheim Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8346-2037","authenticated-orcid":false,"given":"Tim","family":"Heise","sequence":"additional","affiliation":[{"name":"Profil  Neuss Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,12,22]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2009-0370"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2009-2105"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1530\/EJE-19-0901"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2009.09.024"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1053\/beem.2000.0119"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-014-3228-6"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1210\/jcem.86.3.7453"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/oby.2007.233"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.2337\/db10-0726"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.2337\/db08-0969"},{"issue":"5","key":"e_1_2_8_12_1","first-page":"69","article-title":"The treatment of type 2 diabetes","volume":"111","author":"Pfeiffer AF","year":"2014","journal-title":"Dtsch Arztebl Int"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc21-S009"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.2337\/db08-1404"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2002-021194"},{"issue":"11","key":"e_1_2_8_16_1","first-page":"3155","article-title":"Carbenoxolone increases hepatic insulin sensitivity in man: a novel role for 11\u2010oxosteroid reductase in enhancing glucocorticoid receptor activation","volume":"80","author":"Walker BR","year":"1995","journal-title":"J Clin Endocrinol Metab"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/dom.12317"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40842-021-00130-x"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1055\/a-1932-3136"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1210\/jcem.83.4.4706"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc09-2315"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jash.2011.01.009"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.metabol.2020.154246"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1111\/cts.12618"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1530\/EJE-21-1197"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/dom.14646"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1210\/clinem\/dgab450"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.13699"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0306996101"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.54.3.872"},{"issue":"1","key":"e_1_2_8_31_1","first-page":"A99","article-title":"INCB013739, a selective inhibitor of 11\u03b2\u2010hydroxysteroid dehydrogenase type 1 (11\u03b2HSD1), improves insulin sensitivity and lowers plasma cholesterol over 28\u2009days in patients with type 2 diabetes mellitus","volume":"57","author":"Hawkins M","year":"2008","journal-title":"Diabetes"},{"key":"e_1_2_8_32_1","unstructured":"RosenstockJ BanarerS FonsecaV et al.Efficacy and safety of the 11\u2010beta\u2010HSD1 inhibitor INCB13739 added to metformin therapy in patients with type 2 diabetes. 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