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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\u003EThis article discusses evidence supporting the efforts to develop longer-acting insulin therapy. The importance of insulin therapy and associated glycemic control is incontestable. Prior to the discovery of insulin in the early 1920s, the life expectancy of a 10-year-old diagnosed with type 1 diabetes was only 2.6 years. In the early years following the introduction of insulin, the life expectancy of a 10-year-old patient with diabetes had increased to 24.3 years and had leapt to 55 years 2 decades later [Joslin EP. \u003Cem\u003EDiabetic Manual for the Doctor and Patient\u003C\/em\u003E, 9th Ed. 1957].\u003C\/p\u003E\n         \u003C\/div\u003E\u003Cul class=\u0022kwd-group\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003EInsulin\u003C\/li\u003E\u003C\/ul\u003E\u003Cul class=\u0022kwd-group clinical-trial\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003EInsulin\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EEndocrinology\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EDiabetes \u0026amp; Metabolic Syndrome\u003C\/li\u003E\u003C\/ul\u003E\u003Cp id=\u0022p-2\u0022\u003ELuigi Meneghini, MD, University of Miami, Miami, Florida, USA, presented evidence supporting the efforts to develop longer-acting insulin therapy.\u003C\/p\u003E\u003Cp id=\u0022p-3\u0022\u003EThe importance of insulin therapy and associated glycemic control is incontestable. Prior to the discovery of insulin in the early 1920s, the life expectancy of a 10-year-old diagnosed with type 1 diabetes was only 2.6 years. In the early years following the introduction of insulin, the life expectancy of a 10-year-old patient with diabetes had increased to 24.3 years and had leapt to 55 years 2 decades later [Joslin EP. \u003Cem\u003EDiabetic Manual for the Doctor and Patient\u003C\/em\u003E, 9th Ed. 1957].\u003C\/p\u003E\u003Cp id=\u0022p-4\u0022\u003EEstablishing glycemic control early in the course of diabetes reduces vascular complications later in life [UKPDS Group. \u003Cem\u003ELancet\u003C\/em\u003E 1998; Gerstein HC et al. \u003Cem\u003EN Engl J Med\u003C\/em\u003E 2008; Duckworth W et al. \u003Cem\u003EN Engl J Med\u003C\/em\u003E 2009; ACCORD Study Group. \u003Cem\u003EN Engl J Med\u003C\/em\u003E 2010]. However, insulin therapy does have limitations. One is the risk of hypoglycemia. Hypoglycemia, which most often occurs in individuals with diabetes who require insulin, accounted for \u0026gt;95% of all endocrine-related emergency hospitalizations in people aged \u0026gt;65 years in the United States from 2007 through 2009 [Budnitz DS et al. \u003Cem\u003EN Engl J Med\u003C\/em\u003E 2011]. The frequency of severe episodes of hypoglycemia rises with duration of both type 1 and type 2 diabetes [UK Hypoglycemia Study Group. \u003Cem\u003EDiabetologia\u003C\/em\u003E 2007; Amiel SA et al. \u003Cem\u003EDiab Med\u003C\/em\u003E 2008]. There is also increasing awareness of asymptomatic hypoglycemia, especially occurring during the night, as evidenced by data collected through continuous glucose monitoring [Hay LC et al. \u003Cem\u003EDiab Tech Ther\u003C\/em\u003E 2003].\u003C\/p\u003E\u003Cp id=\u0022p-5\u0022\u003ELonger-acting (\u226524 hours) insulin could be useful especially when accompanied by minimal-to-no peak effect and predictable day-to-day glucose response. Insulin detemir and insulin glargine have shown promise towards these goals, although the peak effect has only been reduced but not eliminated, compared with neutral protamine Hagedorn (NPH) insulin [Heise T et al. \u003Cem\u003EDiabetes\u003C\/em\u003E 2004]. Nocturnal hypoglycemia is reduced with insulin glargine and insulin detemir, compared with NPH insulin [Riddle MC et al. \u003Cem\u003EDiab Care\u003C\/em\u003E 2003; Philis-Tsimikas A et al. \u003Cem\u003EClin Ther\u003C\/em\u003E 2006].\u003C\/p\u003E\u003Cp id=\u0022p-6\u0022\u003EIn seeking to extend the benefits of basal insulin, studies have focused on larger molecules that have a longer duration of action, such as the multihexameric insulin degludec. Insulin degludec attains steady state with 2 to 3 days of once-daily dosing. Compared with insulin glargine, insulin degludec maintains a more sustained serum concentration over time, a longer mean half-life (\u003Ca id=\u0022xref-table-wrap-1-1\u0022 class=\u0022xref-table\u0022 href=\u0022#T1\u0022\u003ETable 1\u003C\/a\u003E).\u003C\/p\u003E\u003Cdiv id=\u0022T1\u0022 class=\u0022table pos-float\u0022\u003E\u003Cdiv class=\u0022table-inline\u0022\u003E\u003Cdiv class=\u0022callout\u0022\u003E\u003Cspan\u003EView this table:\u003C\/span\u003E\u003Cul class=\u0022callout-links\u0022\u003E\u003Cli class=\u00220 first\u0022\u003E\u003Ca href=\u0022\/\u0022 class=\u0022table-expand-inline\u0022 data-table-url=\u0022\/highwire\/markup\/13818\/expansion?postprocessors=highwire_figures%2Chighwire_math%2Chighwire_inline_linked_media%2Chighwire_embed\u0026amp;table-expand-inline=1\u0022 html=\u00221\u0022 fragment=\u0022#\u0022 external=\u00221\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView inline\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00221\u0022\u003E\u003Ca href=\u0022\/highwire\/markup\/13818\/expansion?width=1000\u0026amp;height=500\u0026amp;iframe=true\u0026amp;postprocessors=highwire_figures%2Chighwire_math%2Chighwire_inline_linked_media\u0022 class=\u0022colorbox colorbox-load table-expand-popup\u0022 rel=\u0022gallery-fragment-tables\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView popup\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00222 last\u0022\u003E\u003Ca href=\u0022\/highwire\/powerpoint\/13818\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\u003C\/div\u003E\u003Cdiv class=\u0022table-caption\u0022\u003E\u003Cspan class=\u0022table-label\u0022\u003ETable 1.\u003C\/span\u003E \n            \u003Cp id=\u0022p-7\u0022 class=\u0022first-child\u0022\u003EHalf-life of Insulin Degludec and Insulin Glargine\u003C\/p\u003E\n         \u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cp id=\u0022p-8\u0022\u003ECompound LY2605541 (pegylated lispro insulin) is another large molecule that is delayed in absorption and clearance, which prolongs its action.\u003C\/p\u003E\u003Cp id=\u0022p-9\u0022\u003EThese ultra long-acting insulin preparations have been compared with insulin glargine with regards to efficacy and risk of hypoglycemia. While there is comparable reduction in HbA1C between these longer-acting basal analogs and insulin glargine, there is also a consistent reduction in the risk of nocturnal hypoglycemia associated with the use of these new ultra-long basal insulin preparations [Rodbard HW et al. \u003Cem\u003EDiabet Med\u003C\/em\u003E 2013; Bergenstal RM et al. \u003Cem\u003EDiabetes Care\u003C\/em\u003E 2012].\u003C\/p\u003E\u003Cp id=\u0022p-10\u0022\u003EBecause these longer-acting insulin preparations take \u223c3 to 4 dosing injections to reach steady state, adjusting the basal insulin dose on a weekly basis to achieve desired fasting plasma glucose targets should allay any potential concerns over stacking of the insulin.\u003C\/p\u003E\u003Cp id=\u0022p-11\u0022\u003ELong-term cardiovascular trials planned for some of these longer-acting basal insulin preparations should be able to address any remaining issues regarding the cardiovascular safety of these novel insulin molecules.\u003C\/p\u003E\u003Cul class=\u0022copyright-statement\u0022\u003E\u003Cli class=\u0022fn\u0022 id=\u0022copyright-statement-1\u0022\u003E\u00a9 2013 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\/13\/17\/37.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_openurl.js?nznlx1\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_tables.js?nznlx1\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}