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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 cardiovascular (CV) safety of linagliptin, a dipeptidyl peptidase-4 inhibitor, in patients with type 2 diabetes mellitus has been supported by a pooled comprehensive analysis of prospectively adjudicated CV events in Phase 3 studies. CV benefit with linagliptin is being tested prospectively in the CAROLINA study [\u003Ca class=\u0022external-ref external-ref-type-clintrialgov\u0022 href=\u0022\/lookup\/external-ref?link_type=CLINTRIALGOV\u0026amp;access_num=NCT01243424\u0026amp;atom=%2Fspmdc%2F13%2F17%2F15.atom\u0022\u003ENCT01243424\u003C\/a\u003E] against glimepiride and in the CARMELINA study [\u003Ca class=\u0022external-ref external-ref-type-clintrialgov\u0022 href=\u0022\/lookup\/external-ref?link_type=CLINTRIALGOV\u0026amp;access_num=NCT01897532\u0026amp;atom=%2Fspmdc%2F13%2F17%2F15.atom\u0022\u003ENCT01897532\u003C\/a\u003E] against placebo. The pooled analysis included 9459 patients from 19 United States or multinational, multicenter, double-blind, parallel-group studies.\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\u003EMyocardial Infarction\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EDiabetes \u0026amp; Endocrinology Clinical Trials\u003C\/li\u003E\u003C\/ul\u003E\u003Cul class=\u0022kwd-group clinical-trial\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003EEndocrinology\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EDiabetes \u0026amp; Metabolic Syndrome\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EDiabetes Mellitus\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EMyocardial Infarction\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EDiabetes \u0026amp; Endocrinology Clinical Trials\u003C\/li\u003E\u003C\/ul\u003E\u003Cp id=\u0022p-2\u0022\u003EThe cardiovascular (CV) safety of linagliptin, a dipeptidyl peptidase-4 inhibitor, in patients with type 2 diabetes mellitus (T2DM) has been supported by a pooled comprehensive analysis of prospectively adjudicated CV events in Phase 3 studies. Odd Erik Johansen, MD, Boehringer-Ingelheim, Asker, Norway, presented the analysis.\u003C\/p\u003E\u003Cp id=\u0022p-3\u0022\u003EThe present analysis expands on a previous assessment that showed the CV safety of linagliptin, and a hint of a benefit [Johansen OE et al. \u003Cem\u003ECardiovasc Diabetol\u003C\/em\u003E 2012], by including recently completed trials with linagliptin. The possibility of CV benefit was also shown in a head-to-head comparison of linagliptin and glimeperide in a noninferiority trial [Gallwitz B et al. \u003Cem\u003ELancet\u003C\/em\u003E 2012]. CV benefit with linagliptin is being tested prospectively in the CAROLINA study [\u003Ca class=\u0022external-ref external-ref-type-clintrialgov\u0022 href=\u0022\/lookup\/external-ref?link_type=CLINTRIALGOV\u0026amp;access_num=NCT01243424\u0026amp;atom=%2Fspmdc%2F13%2F17%2F15.atom\u0022\u003ENCT01243424\u003C\/a\u003E] against glimepiride and in the CARMELINA study [\u003Ca class=\u0022external-ref external-ref-type-clintrialgov\u0022 href=\u0022\/lookup\/external-ref?link_type=CLINTRIALGOV\u0026amp;access_num=NCT01897532\u0026amp;atom=%2Fspmdc%2F13%2F17%2F15.atom\u0022\u003ENCT01897532\u003C\/a\u003E] against placebo.\u003C\/p\u003E\u003Cp id=\u0022p-4\u0022\u003EThe pooled analysis included 9459 patients from 19 United States or multinational, multicenter, double-blind, parallel-group studies. Of these, 5847 patients were randomized to receive linagliptin and 3612 to a comparator for at least 12 weeks and up to 2 years. A prospectively defined, blinded, and independent adjudication of events was used. The primary composite endpoint was CV death, myocardial infarction (MI), stroke, and hospitalization for unstable angina pectoris.\u003C\/p\u003E\u003Cp id=\u0022p-5\u0022\u003EIn the pooled analysis, the patients were aged \u223c60 years, \u223c45% were women, and \u223c60% were white. Most patients had normal or mild estimated glomerular filtration rate and had high (\u223c73%) prior use of a CV medication (aspirin, lipid-lowering agent, or antihypertensive). About a quarter (24.5% linagliptin, 29.0% placebo) of the patients had a Framingham Risk Score \u0026gt;15%.\u003C\/p\u003E\u003Cp id=\u0022p-6\u0022\u003EThe drug exposure and the incidence of primary, secondary, and tertiary outcomes in the pooled analysis are detailed in \u003Ca id=\u0022xref-table-wrap-1-1\u0022 class=\u0022xref-table\u0022 href=\u0022#T1\u0022\u003ETable 1\u003C\/a\u003E. Linagliptin, versus the combined comparators, reduced the primary outcome (HR, 0.78; 95% CI, 0.55 to 1.12) and the secondary outcome of CV death, stroke, or MI (HR, 0.74; 95% CI, 0.49 to 1.13). Significant reductions were achieved with linagliptin versus the combined comparators for nonfatal stroke (HR, 0.34; 95% CI, 0.15 to 0.75; p\u0026lt;0.05), and transischemic attack (HR, 0.09; 95% CI, 0.01 to 0.75; p\u0026lt;0.05).\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\/13799\/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\/13799\/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\/13799\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\u003EDrug Exposure, Incidence, and Incidence Rates of Cardiovascular Endpoints\u003C\/p\u003E\n         \u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cp id=\u0022p-9\u0022\u003EA placebo cohort analysis included 7746 patients from 18 United States or multinational, double-blind, parallel-group studies, of whom 5071 were randomized to linagliptin and 2675 to placebo. In this placebo cohort, from which one active comparator trial was removed, there were fewer primary and secondary outcome events. Linagliptin did not affect the primary outcome compared with placebo (HR, 1.09; 95% CI, 0.68 to 1.75).\u003C\/p\u003E\u003Cp id=\u0022p-10\u0022\u003EHospitalization for congestive heart failure was assessed in 8 of the trials, which occurred in 12 of 1834 patients (0.7%) in the linagliptin group and 9 of 1175 patients (0.8%) in the comparator groups. The incidence rate per 1000 years at risk was 9.5% and 8.8%, respectively. Linagliptin did not reduce hospitalization for heart failure (HR, 1.04; 95% CI, 0.43 to 2.47).\u003C\/p\u003E\u003Cp id=\u0022p-11\u0022\u003EThus, in a representative cohort of patients with T2DM, with a diverse background from low to high CV risk and concomitant treatments from treatment-na\u00efve to insulin, linagliptin was not associated with an increased risk for CV events. Based on the limited number of congestive heart failure cases leading to hospitalization, no increased risk with linagliptin was observed.\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\/15.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?nznl82\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?nznl82\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}