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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 once-weekly formulation of exenatide, a glucagon-like peptide-1 receptor agonist, is associated with clinically sustained improvement in glycemic control, continued improvements in cardiometabolic risk factors and weight loss after 4 years of treatment in type 2 diabetes mellitus (T2DM) patients. This article discusses results of the open-label extension of the Effects of Exenatide Long-Acting Release on Glucose Control and Safety in Subjects with Type 2 Diabetes Mellitus [DURATION-1; \u003Ca class=\u0022external-ref external-ref-type-clintrialgov\u0022 href=\u0022\/lookup\/external-ref?link_type=CLINTRIALGOV\u0026amp;access_num=NCT00308139\u0026amp;atom=%2Fspmdc%2F12%2F16%2F13.atom\u0022\u003ENCT00308139\u003C\/a\u003E] clinical trial.\u003C\/p\u003E\n         \u003C\/div\u003E\u003Cul class=\u0022kwd-group\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003EDiabetes Mellitus\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003ECardiometabolic Disorder\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EDiabetes \u0026amp; Endocrinology Clinical Trials\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EObesity Diabetes \u0026amp; Metabolic Syndrome\u003C\/li\u003E\u003C\/ul\u003E\u003Cp id=\u0022p-2\u0022\u003EThe once-weekly formulation of exenatide, a glucagon-like peptide-1 receptor agonist, is associated with clinically sustained improvement in glycemic control, continued improvements in cardiometabolic risk factors and weight loss after 4 years of treatment in type 2 diabetes mellitus (T2DM) patients. Results of the open-label extension of the Effects of Exenatide Long-Acting Release on Glucose Control and Safety in Subjects with Type 2 Diabetes Mellitus [DURATION-1; \u003Ca class=\u0022external-ref external-ref-type-clintrialgov\u0022 href=\u0022\/lookup\/external-ref?link_type=CLINTRIALGOV\u0026amp;access_num=NCT00308139\u0026amp;atom=%2Fspmdc%2F12%2F16%2F13.atom\u0022\u003ENCT00308139\u003C\/a\u003E] clinical trial were presented by Leigh MacConell, PhD, Amylin Pharmaceuticals, San Diego, California, USA.\u003C\/p\u003E\u003Cp id=\u0022p-3\u0022\u003EIn the DURATION-1 trial, treatment with exenatide once weekly (EQW) for 30 weeks significantly reduced HbA1C compared with twice-daily exenatide in patients with T2DM [Drucker DJ et al. \u003Cem\u003ELancet\u003C\/em\u003E 2008]. The study included patients with T2DM and HbA1C 7.1% to 11.0%, who were treated with diet and exercise and\/or a stable dose of metformin, sulfonylurea, thiazolidinedione, or a combination of these therapies. Patients were randomized to receive EQW (2 mg) or exenatide BID (5 \u03bcg for 4 weeks, then 10 \u03bcg for 26 weeks). The primary endpoint (HbA1C) was assessed at 30 weeks, after which all patients received EQW (2 mg).\u003C\/p\u003E\u003Cp id=\u0022p-4\u0022\u003EThe objectives of the current analysis were to examine the long-term safety and efficacy of EQW over 4 years in patients with T2DM. Study endpoints included change from baseline to Year 4 in HbA1C, fasting plasma glucose (FPG), weight, blood pressure (BP), and lipid profile. Sixty percent (n=176) of the intention-to-treat (ITT) population completed 4 years of EQW treatment. The efficacy results are based on the 176 study completers. Safety data are based on the ITT population (n=295). Baseline characteristics were consistent between the ITT and completer populations: mean age 56 years, 54% men, mostly white, mean HbA1C 8.2%, mean FPG 9.2 mmol\/L, and duration of diabetes 7 years. Most study participants received metformin (33%) or combination therapies (39%).\u003C\/p\u003E\u003Cp id=\u0022p-5\u0022\u003EAt 4 years, mean HbA1C (\u00b1 standard error) was 6.9% (\u00b10.1%), with 55% of patients achieving HbA1C \u0026lt;7.0% and 36% achieving HbA1C \u22646.5% (\u003Ca id=\u0022xref-fig-1-1\u0022 class=\u0022xref-fig\u0022 href=\u0022#F1\u0022\u003EFigure 1\u003C\/a\u003E). Clinically significant (p\u0026lt;0.05) improvements in FPG (\u22121.9 mmol) and weight (\u22122.5 kg) were observed. Improvements in \u03b2-cell function and insulin sensitivity were indicated by increases in the Homeostasis Model Assessment for \u03b2-cell function (HOMA-B; 26%\u00b16%) and for insulin sensitivity (HOMA-S; 13%\u00b13%). These changes from baseline were observed at Year 1 and maintained thereafter.\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\/13\/F1.large.jpg?width=800\u0026amp;height=600\u0026amp;carousel=1\u0022 title=\u0022Once-Weekly Exenatide Associated with Improved HbA1C and Fasting Plasma Glucose Through 4 Years.\u0022 class=\u0022fragment-images colorbox-load\u0022 rel=\u0022gallery-fragment-images-1074474193\u0022 data-figure-caption=\u0022Once-Weekly Exenatide Associated with Improved HbA1C and Fasting Plasma Glucose Through 4 Years.\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\/13\/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\/13\/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\/13\/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\/13045\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-6\u0022 class=\u0022first-child\u0022\u003EOnce-Weekly Exenatide Associated with Improved HbA1C and Fasting Plasma Glucose Through 4 Years.\u003C\/p\u003E\n         \u003Cq class=\u0022attrib\u0022 id=\u0022attrib-1\u0022\u003EFPG=fasting plasma glucose; HOMA-B=Homeostasis Model Assessment B-cell function; HOMA-S=Homeostasis Model Assessment, insulin sensitivity; SE=standard error.\u003C\/q\u003E\u003Cq class=\u0022attrib\u0022 id=\u0022attrib-2\u0022\u003EReproduced with permission from Amylin Pharmaceuticals.\u003C\/q\u003E\u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cp id=\u0022p-7\u0022\u003EImprovements (baseline to 4 years) were also observed for cardiovascular risk markers: systolic BP (\u22121.6 mm Hg; \u22128.7 mm Hg in patients with abnormal baseline systolic BP), diastolic BP (\u22122.7 mm Hg), total cholesterol (\u22120.30 mmol\/L), low-density lipoprotein cholesterol (\u22120.20 mmol\/L), high-density lipoprotein cholesterol (+0.05 mmol\/L), and triglycerides (\u221213%). Maximum response was seen at Year 2 and maintained thereafter. Seventy-one percent of patients lost weight (\u22122.5 kg mean weight loss at Year 4).\u003C\/p\u003E\u003Cp id=\u0022p-8\u0022\u003ENausea and injection-site pruritus\u2014the most common adverse events (AEs)\u2014decreased in incidence with ongoing therapy, as did vomiting and diarrhea. The annual event rate for nausea and injection-site pruritus was 15\/100 years and 6\/100 years patient exposure over the 4-year study duration. Cardiac and renal\/urinary disorders occurred at event rates of 5 and 6 per 100 years patient exposure, respectively. Twenty percent of EQW patients experienced serious AEs (no identifiable pattern of types of events) and 3 patients died (none due to treatment). Withdrawal rates over the 4-year duration due to AEs were low (8%); gastrointestinal AEs led to withdrawal in few (2%) patients. There was no major hypoglycemia. Minor hypoglycemia increased minimally after 1 year of exenatide therapy. There were few minor hypoglycemia events in patients not using concomitant sulfonylurea.\u003C\/p\u003E\u003Cp id=\u0022p-9\u0022\u003ELong-term exenatide treatment was associated with significant, sustained improvement in glycemic control and improvements in cardiometabolic measures, with no unexpected safety findings.\u003C\/p\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\/13.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?nzn8hp\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?nzn8hp\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}