{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T23:05:32Z","timestamp":1785539132784,"version":"3.56.0"},"reference-count":27,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2017,3,27]],"date-time":"2017-03-27T00:00:00Z","timestamp":1490572800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100004312","name":"Eli Lilly and Company","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100004312","id-type":"DOI","asserted-by":"crossref"}]}],"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 assess the effect of\n LY2409021<\/jats:styled-content>\n on systolic blood pressure (\n SBP<\/jats:styled-content>\n ) in patients with type 2 diabetes.\n <\/jats:p>\n <\/jats:sec>\n \n Materials and methods<\/jats:title>\n \n This 6\u2010week, randomized, crossover study evaluated the effects of once\u2010daily administration of\n LY2409021<\/jats:styled-content>\n 20\u2009mg vs those of placebo on\n SBP<\/jats:styled-content>\n , diastolic\n BP<\/jats:styled-content>\n (\n DBP<\/jats:styled-content>\n ), and mean arterial pressure (\n MAP<\/jats:styled-content>\n ) using 24\u2010hour ambulatory\n BP<\/jats:styled-content>\n monitoring (\n ABPM<\/jats:styled-content>\n ) in 270 subjects treated with diet\/exercise\u2009\u00b1\u2009metformin. Other measures included changes in glycemic control, serum lipids, and hepatic safety markers.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n At 6\u2009weeks of\n LY2409021<\/jats:styled-content>\n treatment, 24\u2010hour mean\n SBP<\/jats:styled-content>\n was increased, with a least squares mean (\n LSM<\/jats:styled-content>\n ) difference of 2.26\u2009mm\n H<\/jats:styled-content>\n g vs placebo (95%\n CI<\/jats:styled-content>\n : 1.11, 3.40;\n \n P<\/jats:styled-content>\n <\/jats:italic>\n \u2009<\u2009.001). The 24\u2010hour mean\n DBP<\/jats:styled-content>\n and\n MAP<\/jats:styled-content>\n also increased, with\n LSM<\/jats:styled-content>\n differences of 1.37\u2009mm\n H<\/jats:styled-content>\n g (95%\n CI<\/jats:styled-content>\n : 0.66, 2.08;\n \n P<\/jats:styled-content>\n <\/jats:italic>\n \u2009<\u2009.001) and 1.67\u2009mm\n H<\/jats:styled-content>\n g (95%\n CI<\/jats:styled-content>\n : 0.86, 2.47;\n \n P<\/jats:styled-content>\n <\/jats:italic>\n \u2009<\u2009.001) vs placebo, respectively. At week 6,\n LY2409021<\/jats:styled-content>\n treatment reduced glycated hemoglobin (\n HbA1c<\/jats:styled-content>\n ) levels, with an\n LSM<\/jats:styled-content>\n difference of \u22120.49% (\u22125.4\u2009mmol\/mol) (95%\n CI<\/jats:styled-content>\n : \u22120.56%, \u22120.42% [\u22126.1, \u22124.6\u2009mmol\/mol];\n \n P<\/jats:styled-content>\n <\/jats:italic>\n \u2009<\u2009.001) vs placebo. Mean\n HbA1c<\/jats:styled-content>\n at baseline was 7.3% (56\u2009mmol\/mol). Small but significant changes in serum lipid and aminotransferase levels were observed with\n LY2409021<\/jats:styled-content>\n treatment (all\n \n P<\/jats:styled-content>\n <\/jats:italic>\n \u2009<\u2009.05 vs placebo).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n Statistically significant increases in\n BP<\/jats:styled-content>\n ,\n MAP<\/jats:styled-content>\n and serum lipid levels were observed with\n LY2409021<\/jats:styled-content>\n treatment at a dose that lowered\n HbA1c<\/jats:styled-content>\n and glucose levels. These effects may limit the clinical utility of\n LY2409021<\/jats:styled-content>\n as a chronic treatment for type 2 diabetes.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/dom.12904","type":"journal-article","created":{"date-parts":[[2017,2,13]],"date-time":"2017-02-13T11:06:38Z","timestamp":1486983998000},"page":"1071-1077","source":"Crossref","is-referenced-by-count":36,"title":["Treatment with the glucagon receptor antagonist\n LY2409021<\/scp>\n increases ambulatory blood pressure in patients with type 2 diabetes"],"prefix":"10.1111","volume":"19","author":[{"given":"Christof M.","family":"Kazda","sequence":"first","affiliation":[{"name":"Eli Lilly and Company Neuilly\u2010sur\u2010Seine France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Frias","sequence":"additional","affiliation":[{"name":"National Research Institute Los Angeles California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irene","family":"Foga","sequence":"additional","affiliation":[{"name":"Eli Lilly and Company Danforth Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuewei","family":"Cui","sequence":"additional","affiliation":[{"name":"Eli Lilly and Company Indianapolis Indiana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina B.","family":"Guzman","sequence":"additional","affiliation":[{"name":"Eli Lilly and Company Indianapolis Indiana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Parag","family":"Garhyan","sequence":"additional","affiliation":[{"name":"Eli Lilly and Company Indianapolis Indiana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cory","family":"Heilmann","sequence":"additional","affiliation":[{"name":"Eli Lilly and Company Indianapolis Indiana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jihui Anne","family":"Yang","sequence":"additional","affiliation":[{"name":"Eli Lilly and Company Indianapolis Indiana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas A.","family":"Hardy","sequence":"additional","affiliation":[{"name":"Eli Lilly and Company Indianapolis Indiana"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,3,27]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00529.2004"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1517\/14728222.9.3.593"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI60016"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM197007162830301"},{"key":"e_1_2_6_6_1","doi-asserted-by":"crossref","first-page":"489","DOI":"10.2337\/diab.31.6.489","article-title":"Glucose modulation of insulin and glucagon secretion in nondiabetic and diabetic man","volume":"31","author":"Hollander PM","year":"1982","journal-title":"Diabetes"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1210\/jcem-58-3-449"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1210\/er.2006-0026"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.49.8.1367"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.85.11.4053"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1463-1326.2011.01427.x"},{"issue":"1","key":"e_1_2_6_12_1","first-page":"A115","article-title":"The glucagon receptor antagonist LY2409021 attenuates increases in hepatic glucose output (HGO) and blood glucose during hyperglucagonemia in healthy male patients (Abstract 416\u2010PP)","volume":"60","author":"Tham LS","year":"2011","journal-title":"Diabetes"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/dom.12446"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc15-1643"},{"issue":"1","key":"e_1_2_6_15_1","first-page":"A85","article-title":"Inhibition of glucagon\u2010induced hyperglycemia predicts glucose lowering efficacy of a glucagon receptor antagonist, MK\u20100893, in type 2 diabetes (T2DM) (Abstract 311\u2010OR)","volume":"60","author":"Ruddy M","year":"2011","journal-title":"Diabetes"},{"key":"e_1_2_6_16_1","unstructured":"Eli Lilly and Company.A phase 2 double\u2010blind placebo\u2010controlled trial to evaluate the safety and efficacy of LY2409021 compared to sitagliptin in subjects with type 2 diabetes mellitus.ClinicalTrials.govidentifier: NCT02111096 registered April 8 2014.https:\/\/clinicaltrials.gov\/ct2\/show\/NCT02111096. 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