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type=\u0022text\/css\u0022 rel=\u0022stylesheet\u0022 href=\u0022\/\/d282kpwvnogo5m.cloudfront.net\/sites\/default\/files\/cdn\/css\/http\/css_Xg7z6oCTVgud_Q0huYz9x9iiD5H_2YPSJ5z2ZViSWdY.css\u0022 media=\u0022all\u0022 \/\u003E\n\u003Clink rel=\u0027stylesheet\u0027 type=\u0027text\/css\u0027 href=\u0027\/sites\/all\/modules\/contrib\/panels\/plugins\/layouts\/onecol\/onecol.css\u0027 \/\u003E\u003C\/head\u003E\u003Cbody\u003E\u003Cdiv class=\u0022panels-ajax-tab-panel panels-ajax-tab-panel-sageoa-tab-art\u0022\u003E\u003Cdiv class=\u0022panel-display panel-1col clearfix\u0022 \u003E\n  \u003Cdiv class=\u0022panel-panel panel-col\u0022\u003E\n    \u003Cdiv\u003E\u003Cdiv class=\u0022panel-pane pane-highwire-markup\u0022 \u003E\n  \n      \n  \n  \u003Cdiv class=\u0022pane-content\u0022\u003E\n    \u003Cdiv class=\u0022highwire-markup\u0022\u003E\u003Cdiv xmlns=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022 id=\u0022content-block-markup\u0022 xmlns:xhtml=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022\u003E\u003Cdiv class=\u0022article fulltext-view \u0022\u003E\u003Cspan class=\u0022highwire-journal-article-marker-start\u0022\u003E\u003C\/span\u003E\u003Cdiv class=\u0022section abstract\u0022 id=\u0022abstract-1\u0022\u003E\u003Ch2\u003ESummary\u003C\/h2\u003E\n            \u003Cp id=\u0022p-1\u0022\u003EThe glucagon receptor antagonist LY2409021 (LY) substantially lowers HbA1C without severe hypoglycemia or weight gain in type 2 diabetes mellitus (T2DM) patients. In a double-blind, randomized, placebo-controlled, Phase 2 study researchers examined the margin between LY efficacy and safety by comparing mean changes in HbA1C and liver aminotransferases at 3 dose levels.\u003C\/p\u003E\n         \u003C\/div\u003E\u003Cul class=\u0022kwd-group\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003EDiabetes \u0026amp; Endocrinology Clinical Trials\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EHyperglycemia\/Hypoglycemia\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EDiabetes Mellitus\u003C\/li\u003E\u003C\/ul\u003E\u003Cp id=\u0022p-2\u0022\u003EThe glucagon receptor antagonist LY2409021 (LY) substantially lowers HbA1C without severe hypoglycemia or weight gain in type 2 diabetes mellitus (T2DM) patients. In a double-blind, randomized, placebo-controlled, Phase 2 study presented by Christof M. Kazda, MD, Eli Lilly and Company, Suresnes, France, researchers examined the margin between LY efficacy and safety by comparing mean changes in HbA1C and liver aminotransferases at 3 dose levels.\u003C\/p\u003E\u003Cp id=\u0022p-3\u0022\u003ET2DM pathophysiology is characterized by greater postprandial glucose release, impaired insulin secretion, and abnormal glucagon plasma levels [Woerle HJ et al. \u003Cem\u003EAm J Physiol Endocrinol Metab\u003C\/em\u003E 2006]. LY is a potent, selective glucagon receptor antagonist that inhibits hepatic glucose output and has significant glucose-lowering effects [Kelly RP et al. ADA 2011 Abstract 1004-P; Tham LS et al. ADA 2011 Abstract 416-PP]. In a Phase 1 study [\u003Ca class=\u0022external-ref external-ref-type-clintrialgov\u0022 href=\u0022\/lookup\/external-ref?link_type=CLINTRIALGOV\u0026amp;access_num=NCT01606397\u0026amp;atom=%2Fspmdc%2F12%2F16%2F16.atom\u0022\u003ENCT01606397\u003C\/a\u003E], LY improved glycemic parameters and showed reversible dose-dependent increases in serum aminotransferase levels. The incidence of hypoglycemia was infrequent and was considered to be of mild to moderate intensity [Kelly RP et al. ADA 2011 Abstract 305-OR].\u003C\/p\u003E\u003Cp id=\u0022p-4\u0022\u003EThe primary endpoint of the current Phase 2a study [\u003Ca class=\u0022external-ref external-ref-type-clintrialgov\u0022 href=\u0022\/lookup\/external-ref?link_type=CLINTRIALGOV\u0026amp;access_num=NCT00871572\u0026amp;atom=%2Fspmdc%2F12%2F16%2F16.atom\u0022\u003ENCT00871572\u003C\/a\u003E] was mean change in HbA1C and liver aminotransferases. Secondary objectives included the evaluation of LY effects on blood glucose, insulin, glucagon, glucagon-like peptide-1 (GLP-1), and blood lipids, as well as safety and tolerability.\u003C\/p\u003E\u003Cp id=\u0022p-5\u0022\u003EPatients aged 18 to 70 years with T2DM (HbA1C 6.5% to 10%) and a body mass index of 25 to 40 kg\/m\u003Csup\u003E2\u003C\/sup\u003E who were treated with diet and exercise alone, or with a stable dose of metformin (\u22651000 mg\/day for \u22653 months prior to screening) were eligible. Key exclusion criteria were related to hepatic diseases. Subjects (mean age 50 years, mean diabetes duration between 3 and 5 years) were randomly assigned to LY 10 mg (n=17), 30 mg (n=34), 60 mg (n=26), or placebo (n=10) QD for 12 weeks. There were 52.9% to 58.8% of the LY patients taking metformin versus 70% of placebo subjects. Mean baseline HbA1C was highest in the LY 10-mg group (8%) and 7.5%, 7.6%, and 7.8% in the 30-mg, 60-mg, and placebo groups, respectively.\u003C\/p\u003E\u003Cp id=\u0022p-6\u0022\u003EAt Week 12, HbA1C change from baseline showed that LY was associated with significant (p\u22640.05) dose-dependent improvements in glycemic control in contrast to placebo (\u003Ca id=\u0022xref-fig-1-1\u0022 class=\u0022xref-fig\u0022 href=\u0022#F1\u0022\u003EFigure 1\u003C\/a\u003E). LY also produced dose-dependent increases in fasting glucagon, alanine aminotransferase, aspartate aminotransferase, and total GLP-1 that returned to baseline after LY washout.\u003C\/p\u003E\u003Cdiv id=\u0022F1\u0022 class=\u0022fig pos-float  odd\u0022\u003E\u003Cdiv class=\u0022highwire-figure\u0022\u003E\u003Cdiv class=\u0022fig-inline-img-wrapper\u0022\u003E\u003Cdiv class=\u0022fig-inline-img\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/12\/16\/16\/F1.large.jpg?width=800\u0026amp;height=600\u0026amp;carousel=1\u0022 title=\u0022miTT Population: Mean Change from Baseline in HbA1C at Week 12.\u0022 class=\u0022fragment-images colorbox-load\u0022 rel=\u0022gallery-fragment-images-1825423403\u0022 data-figure-caption=\u0022miTT Population: Mean Change from Baseline in HbA1C at Week 12.\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003E\u003Cimg class=\u0022fragment-image\u0022 alt=\u0022Figure 1.\u0022 src=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/12\/16\/16\/F1.medium.gif\u0022\/\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cul class=\u0022highwire-figure-links inline\u0022\u003E\u003Cli class=\u00220 first\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/12\/16\/16\/F1.large.jpg?download=true\u0022 class=\u0022highwire-figure-link highwire-figure-link-download\u0022 title=\u0022Download Figure 1.\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload figure\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00221\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/12\/16\/16\/F1.large.jpg\u0022 class=\u0022highwire-figure-link highwire-figure-link-newtab\u0022 target=\u0022_blank\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EOpen in new tab\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00222 last\u0022\u003E\u003Ca href=\u0022\/highwire\/powerpoint\/13050\u0022 class=\u0022highwire-figure-link highwire-figure-link-ppt\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload powerpoint\u003C\/a\u003E\u003C\/li\u003E\u003C\/ul\u003E\u003C\/div\u003E\u003Cdiv class=\u0022fig-caption attrib\u0022\u003E\u003Cspan class=\u0022fig-label\u0022\u003EFigure 1.\u003C\/span\u003E \n            \u003Cp id=\u0022p-7\u0022 class=\u0022first-child\u0022\u003EmiTT Population: Mean Change from Baseline in HbA1C at Week 12.\u003C\/p\u003E\n         \u003Cq class=\u0022attrib\u0022 id=\u0022attrib-1\u0022\u003ELS=least squares; miTT=modified intention-to-treat; MMRM=Mixed Model Repeated Measures.\u003C\/q\u003E\u003Cq class=\u0022attrib\u0022 id=\u0022attrib-2\u0022\u003EReproduced with permission from CM Kazda, MD.\u003C\/q\u003E\u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cp id=\u0022p-8\u0022\u003EThe proportions of patients who experienced any treatment-emergent adverse event (TEAE) were similar in all treatment groups. No severe TEAEs were reported. Two non-drug-related serious adverse events occurred. There were no severe hypoglycemia events and 4 confirmed (blood glucose measurements) hypoglycemia events. Incidence of hypoglycemia was not dose dependent. There were no significant changes from baseline observed in any of the 3 LY treatment groups compared with placebo for body weight, blood pressure, triglycerides, low-density lipoprotein and high-density lipoprotein cholesterol, bilirubin, fasting insulin, or active GLP-1.\u003C\/p\u003E\u003Cp id=\u0022p-9\u0022\u003ETreatment with LY resulted in dose-dependent transient increases in mean aminotransferase, fasting glucagon, and total GLP-1 levels without elevated bilirubin or other signs\/symptoms of liver injury. There were no increases in body weight, lipids, or blood pressure. The efficacy, safety, and tolerability profile of LY in patients with T2DM supports further clinical development.\u003C\/p\u003E\u003Cdiv id=\u0022F2\u0022 class=\u0022fig pos-float  odd\u0022\u003E\u003Cdiv class=\u0022highwire-figure\u0022\u003E\u003Cdiv class=\u0022fig-inline-img-wrapper\u0022\u003E\u003Cdiv class=\u0022fig-inline-img\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/12\/16\/16\/F2.large.jpg?width=800\u0026amp;height=600\u0026amp;carousel=1\u0022 title=\u0022The editors would like to thank the many members of the EASD Congress 2012 presenting faculty who generously gave their time to ensure the accuracy and quality of the articles in this publication.\u0022 class=\u0022fragment-images colorbox-load\u0022 rel=\u0022gallery-fragment-images-1825423403\u0022 data-figure-caption=\u0022The editors would like to thank the many members of the EASD Congress 2012 presenting faculty who generously gave their time to ensure the accuracy and quality of the articles in this publication.\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003E\u003Cimg class=\u0022fragment-image\u0022 alt=\u0022Figure2\u0022 src=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/12\/16\/16\/F2.medium.gif\u0022\/\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cul class=\u0022highwire-figure-links inline\u0022\u003E\u003Cli class=\u00220 first\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/12\/16\/16\/F2.large.jpg?download=true\u0022 class=\u0022highwire-figure-link highwire-figure-link-download\u0022 title=\u0022Download Figure2\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload figure\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00221\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/12\/16\/16\/F2.large.jpg\u0022 class=\u0022highwire-figure-link highwire-figure-link-newtab\u0022 target=\u0022_blank\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EOpen in new tab\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00222 last\u0022\u003E\u003Ca href=\u0022\/highwire\/powerpoint\/13052\u0022 class=\u0022highwire-figure-link highwire-figure-link-ppt\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload powerpoint\u003C\/a\u003E\u003C\/li\u003E\u003C\/ul\u003E\u003C\/div\u003E\u003Cdiv class=\u0022fig-caption\u0022 xmlns:xhtml=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022\u003E\n            \u003Cp id=\u0022p-10\u0022 class=\u0022first-child\u0022\u003EThe editors would like to thank the many members of the EASD Congress 2012 presenting faculty who generously gave their time to ensure the accuracy and quality of the articles in this publication.\u003C\/p\u003E\n         \u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cul class=\u0022copyright-statement\u0022\u003E\u003Cli class=\u0022fn\u0022 id=\u0022copyright-statement-1\u0022\u003E\u00a9 2012 MD Conference Express\u00ae\u003C\/li\u003E\u003C\/ul\u003E\u003Cspan class=\u0022highwire-journal-article-marker-end\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Cspan id=\u0022related-urls\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Ca href=\u0022http:\/\/mdc.sagepub.com\/content\/12\/16\/16.abstract\u0022 class=\u0022hw-link hw-link-article-abstract\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView Summary\u003C\/a\u003E\u003C\/div\u003E  \u003C\/div\u003E\n\n  \n  \u003C\/div\u003E\n\u003C\/div\u003E\n  \u003C\/div\u003E\n\u003C\/div\u003E\n\u003C\/div\u003E\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_figures.js?nzn8q2\u0022\u003E\u003C\/script\u003E\n\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_openurl.js?nzn8q2\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}