{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T22:46:31Z","timestamp":1791499591974,"version":"4.3.4"},"reference-count":24,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2014,6,9]],"date-time":"2014-06-09T00:00:00Z","timestamp":1402272000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100004337","name":"Roche","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004337","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diabetes Obesity Metabolism"],"published-print":{"date-parts":[[2014,11]]},"abstract":"<jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>We assessed safety and efficacy of two selective 11\u03b2\u2010HSD1 inhibitors (RO5093151\/RO\u2010151 and RO5027383\/RO\u2010838) in this randomized, controlled study in metformin\u2010treated patients with type 2 diabetes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Patients either received placebo (N\u2009=\u200921), RO\u2010151 BID 5 mg (N\u2009=\u200924) or 200 mg (N\u2009=\u200920) or RO\u2010838 QD 50 mg (N\u2009=\u200921) or 200 mg (N\u2009=\u200924) for 28 days. Metabolic assessments comprising of nine\u2010point plasma glucose profiles, oral glucose tolerance tests and determination of metabolic biomarkers including insulin, C\u2010peptide, glucagon, HbA1c and lipids were done at baseline and end of treatment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Despite the short treatment duration, both RO\u2010151 and RO\u2010838 showed trends for improved HbA1c and consistent reductions in body weight (\u20130.86 to \u20131.67 kg) exceeding those observed with placebo (\u20130.28 kg, p\u2009=\u20090.019 for 200 mg RO\u2010151 vs. placebo). Insulin sensitivity parameters (e.g. HOMA\u2010IR and Matsuda\u2010Index) improved non\u2010significantly with 200 mg RO\u2010151. Lipid parameters did not consistently improve with either compound, but RO\u2010838 led to non\u2010significant increases in triglycerides and VLDL\u2010cholesterol versus placebo. Both compounds were well tolerated and showed inhibitory effects on 11\u03b2\u2010HSD1 activity based on urinary corticosteroid excretion. As reported for other 11\u03b2\u2010HSD1\u2010inhibitors increased concentrations of ACTH and adrenal androgen precursors were found with RO\u2010151, but not with RO\u2010838.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Slight metabolic improvements were seen, in particular with RO\u2010151 high dose, however, the observed changes often did not reach statistical significance and were not clearly dose dependent. Studies of longer duration are needed to further investigate potential benefits and risks of these compounds.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/dom.12317","type":"journal-article","created":{"date-parts":[[2014,5,14]],"date-time":"2014-05-14T07:58:55Z","timestamp":1400054335000},"page":"1070-1077","source":"Crossref","is-referenced-by-count":44,"title":["Safety, efficacy and weight effect of two 11\u03b2\u2010\n                    <scp>HSD1<\/scp>\n                    inhibitors in metformin\u2010treated patients with type 2 diabetes"],"prefix":"10.1111","volume":"16","author":[{"given":"T.","family":"Heise","sequence":"first","affiliation":[{"name":"Profil  Neuss Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L.","family":"Morrow","sequence":"additional","affiliation":[{"name":"Profil Institute for Clinical Research, Inc.  Chula Vista CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Hompesch","sequence":"additional","affiliation":[{"name":"Profil Institute for Clinical Research, Inc.  Chula Vista CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H.\u2010U.","family":"H\u00e4ring","sequence":"additional","affiliation":[{"name":"Internal Medicine IV University of T\u00fcbingen  T\u00fcbingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"Kapitza","sequence":"additional","affiliation":[{"name":"Profil  Neuss Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Abt","sequence":"additional","affiliation":[{"name":"F. Hoffmann\u2010La Roche, Ltd.  Basel Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Ramsauer","sequence":"additional","affiliation":[{"name":"F. Hoffmann\u2010La Roche, Ltd.  Basel Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.\u2010C.","family":"Magnone","sequence":"additional","affiliation":[{"name":"Roche Pharmaceutical Research and Early Development Roche Innovation Center Basel  Basel Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Fuerst\u2010Recktenwald","sequence":"additional","affiliation":[{"name":"Roche Pharmaceutical Research and Early Development Roche Innovation Center Basel  Basel Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2014,6,9]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.2147\/DMSO.S24022"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.3949\/ccjm.76.s5.06"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd2872"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/0026-0495(81)90224-9"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0163-7258(02)00297-8"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1053\/beem.2000.0119"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M103676200"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1066285"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI17845"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc09-2315"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpdd.5"},{"key":"e_1_2_7_13_1","first-page":"A319","article-title":"Pharmacodynamic effects of AZD4017, a selective 11beta\u2010HSD1 inhibitor, in liver and adipose tissue","volume":"60","author":"Sj\u00f6strand M","year":"2011","journal-title":"Diabetes"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1463-1326.2011.01375.x"},{"key":"e_1_2_7_15_1","unstructured":"Amgen. Amgen Outlines Strategy Growth Objectives and Capital Allocation Plans. Amgen Press Release Dated 21 April2011. Available from URL:http:\/\/www.amgen.com\/media\/media_pr_detail.jsp?releaseID=1553298. 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