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type=\u0022text\/css\u0022 rel=\u0022stylesheet\u0022 href=\u0022\/\/d282kpwvnogo5m.cloudfront.net\/sites\/default\/files\/advagg_css\/css__ce2QY63WIanKyr8eSq7eavr1XQRRmFD6ZSmwpyJi8lM__zXwFqpqmxrZOXXcd_TpBQpjuELbmIP9wBR5UuTDWAO4__YJWWMMdfCJuAFm5cUEp88OsodhO3ZA-2lzRfoBsSlk4.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\u003EType 2 diabetes mellitus (T2DM) is a major risk factor for ischemic heart disease, and cardiovascular disease (CVD) is the leading cause of morbidity and mortality for individuals with T2DM [McEwen LN et al. \u003Cem\u003EDiabetes Care\u003C\/em\u003E 2012]. Common conditions that coexist with T2DM (eg, hypertension and dyslipidemia) are clear risk factors for CVD; however, a diagnosis of T2DM itself confers independent risk [Whittington HJ et al. \u003Cem\u003ECardiol Res Pract\u003C\/em\u003E 2012].\u003C\/p\u003E\n         \u003C\/div\u003E\u003Cul class=\u0022kwd-group\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003ECardiometabolic Disorder\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EDiabetes Mellitus\u003C\/li\u003E\u003C\/ul\u003E\u003Cp id=\u0022p-2\u0022\u003EType 2 diabetes mellitus (T2DM) is a major risk factor for ischemic heart disease, and cardiovascular disease (CVD) is the leading cause of morbidity and mortality for individuals with T2DM [McEwen LN et al. \u003Cem\u003EDiabetes Care\u003C\/em\u003E 2012]. CVD is also the largest contributor to direct and indirect medical costs that are associated with T2DM. Common conditions that coexist with T2DM (eg, hypertension and dyslipidemia) are clear risk factors for CVD; however, a diagnosis of T2DM itself confers independent risk [Whittington HJ et al. \u003Cem\u003ECardiol Res Pract\u003C\/em\u003E 2012].\u003C\/p\u003E\u003Cp id=\u0022p-3\u0022\u003ENumerous studies have demonstrated the efficacy of targeting and controlling individual CV risk factors (eg, blood pressure less than 130\/80 mm Hg, low\u2013density lipoprotein cholesterol less than 100 mg\/dL, HbA1C \u0026lt;7%) in preventing or slowing the progression of microvascular and macrovascular disease in patients with T2DM [American Diabetes Association Standards of Medical Care in Diabetes\u20142012. \u003Cem\u003EDiabetes Care\u003C\/em\u003E 2012] (\u003Ca id=\u0022xref-fig-1-1\u0022 class=\u0022xref-fig\u0022 href=\u0022#F1\u0022\u003EFigure 1\u003C\/a\u003E). Larger benefits are seen when multiple risk factors are globally addressed in patients with T2DM [Buse JB et al. \u003Cem\u003EDiabetes Care\u003C\/em\u003E 2007; Gaede P et al. \u003Cem\u003EN Engl J Med\u003C\/em\u003E 2008].\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\/4\/34\/F1.large.jpg?width=800\u0026amp;height=600\u0026amp;carousel=1\u0022 title=\u0022Metabolic Components of Diabetes: ADA Treatment Recommendations.\u0022 class=\u0022fragment-images colorbox-load\u0022 rel=\u0022gallery-fragment-images-350579121\u0022 data-figure-caption=\u0022Metabolic Components of Diabetes: ADA Treatment Recommendations.\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\/4\/34\/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\/4\/34\/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\/4\/34\/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\/14010\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-4\u0022 class=\u0022first-child\u0022\u003EMetabolic Components of Diabetes: ADA Treatment Recommendations.\u003C\/p\u003E\n         \u003Cq class=\u0022attrib\u0022 id=\u0022attrib-1\u0022\u003EReproduced with permission from EA Oral, MD.\u003C\/q\u003E\u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cp id=\u0022p-5\u0022\u003EHowever, randomized clinical trials have also suggested the limits of intensive CV risk factor control in T2DM [The ACCORD Study Group. \u003Cem\u003EN Engl J Med\u003C\/em\u003E 2010; Duckworth W et al. \u003Cem\u003EN Engl J Med\u003C\/em\u003E 2009; ADVANCE Collaborative Group. \u003Cem\u003EN Engl J Med\u003C\/em\u003E 2008]. In particular, achieving intensive glucose control alone may be insufficient to reduce major CVD events. A new medication class that may reduce CVD in patients with T2DM uses molecules that activate the incretin system to raise or mimic glucagon\u2013like peptide\u20131 (GLP\u20131). In a recent review, Motta et al. [\u003Cem\u003ERecent Pat Cardiovasc Drug Discov\u003C\/em\u003E 2012] reported that incretin\u2013based agents improve glycemic control by mechanisms that minimize hypoglycemia and that some agents also improve lipoprotein profiles, blood pressure control, and weight loss.\u003C\/p\u003E\u003Cp id=\u0022p-6\u0022\u003EGLP\u20131 receptors have been discovered on cardiac myocytes and endothelial cells [Ban K et al. \u003Cem\u003ECirculation\u003C\/em\u003E 2008; Bose AK. \u003Cem\u003EDiabetes\u003C\/em\u003E 2005], and intravenous GLP\u20131 acutely improves left ventricular ejection function (LVEF) and reduces BNP levels in heart failure patients [Sokos GG et al. \u003Cem\u003ECard Fail\u003C\/em\u003E 2006]. A 72\u2013hour GLP\u20131 infusion also improved left ventricular wall motion abnormalities and LVEF in patients with a history of myocardial infarction (MI) [Nikolaidis LA et al. \u003Cem\u003ECirculation\u003C\/em\u003E 2004]. Given all of these favorable effects on surrogate outcomes, there are currently large ongoing trials of GLP\u20131 agonists in patients with T2DM that are studying their ability to reduce CV endpoints [LEADER, \u003Ca class=\u0022external-ref external-ref-type-clintrialgov\u0022 href=\u0022\/lookup\/external-ref?link_type=CLINTRIALGOV\u0026amp;access_num=NCT01179048\u0026amp;atom=%2Fspmdc%2F12%2F4%2F34.atom\u0022\u003ENCT01179048\u003C\/a\u003E; EXSCEL, \u003Ca class=\u0022external-ref external-ref-type-clintrialgov\u0022 href=\u0022\/lookup\/external-ref?link_type=CLINTRIALGOV\u0026amp;access_num=NCT01144338\u0026amp;atom=%2Fspmdc%2F12%2F4%2F34.atom\u0022\u003ENCT01144338\u003C\/a\u003E].\u003C\/p\u003E\u003Cp id=\u0022p-7\u0022\u003EDipeptidyl peptidase 4 (DPP\u20134) inhibitors are another form of incretin\u2013based therapy that indirectly increase endogenous GLP\u20131. Evidence shows that GLP\u20131 receptor agonists and DPP\u20134 inhibitors are capable of preserving myocardial function and protecting cardiac myocytes from ischemic damage, independent of their glucose\u2013lowering function [Mannucci E, Dicembrini I. \u003Cem\u003ECurr Med Res Opin\u003C\/em\u003E 2012].\u003C\/p\u003E\u003Cp id=\u0022p-8\u0022\u003EMannucci and Dicembrini note that both classes of drugs enhance endothelial function. In addition, DPP\u20134 inhibitors increase the availability of endothelial progenitor cells via a GLP\u20131 receptor\u2013independent pathway. Taken together, available experimental evidence, with a few pilot studies in humans, suggests that incretin\u2013based therapies could prevent CVD [Monami M et al. \u003Cem\u003EExp Diabetes Res\u003C\/em\u003E 2011; Phung OJ et al. \u003Cem\u003EJAMA\u003C\/em\u003E 2010; Frederich R et al. \u003Cem\u003EPostgrad Med\u003C\/em\u003E 2010]. As a result, there are several large randomized clinical trials studying the effects of DPP\u20134 inhibitors in patients with T2DM to reduce incident and recurrent CV events [TECOS, \u003Ca class=\u0022external-ref external-ref-type-clintrialgov\u0022 href=\u0022\/lookup\/external-ref?link_type=CLINTRIALGOV\u0026amp;access_num=NCT00790205\u0026amp;atom=%2Fspmdc%2F12%2F4%2F34.atom\u0022\u003ENCT00790205\u003C\/a\u003E; EXAMINE, \u003Ca class=\u0022external-ref external-ref-type-clintrialgov\u0022 href=\u0022\/lookup\/external-ref?link_type=CLINTRIALGOV\u0026amp;access_num=NCT00968708\u0026amp;atom=%2Fspmdc%2F12%2F4%2F34.atom\u0022\u003ENCT00968708\u003C\/a\u003E; SAVOR\u2013TIMI 53, \u003Ca class=\u0022external-ref external-ref-type-clintrialgov\u0022 href=\u0022\/lookup\/external-ref?link_type=CLINTRIALGOV\u0026amp;access_num=NCT01107886\u0026amp;atom=%2Fspmdc%2F12%2F4%2F34.atom\u0022\u003ENCT01107886\u003C\/a\u003E].\u003C\/p\u003E\u003Cp id=\u0022p-9\u0022\u003ENeuroendocrine\u2013based therapies are another approach of interest for reducing CVD in patients with T2DM. Quick\u2013release bromocriptine (bromocriptine\u2013QR) is a D2 dopamine receptor agonist. The Cycloset Safety Trial, a 52\u2013week, randomized, double\u2013blind, multicenter trial demonstrated the potential CV safety and efficacy of this novel therapy for T2DM (\u003Ca id=\u0022xref-fig-2-1\u0022 class=\u0022xref-fig\u0022 href=\u0022#F2\u0022\u003EFigure 2\u003C\/a\u003E) [Gaziano JM et al. \u003Cem\u003EDiabetes Care\u003C\/em\u003E 2010]. Fewer people reported a CVD end point (the composite of MI, stroke, coronary revascularization, and hospitalization for angina or congestive heart failure) in the bromocriptine\u2013QR group (1.8%) versus placebo group (3.2%; HR, 0.60; 95% two\u2013sided CI, 0.35 to 0.96; \u003Ca id=\u0022xref-fig-2-2\u0022 class=\u0022xref-fig\u0022 href=\u0022#F2\u0022\u003EFigure 2\u003C\/a\u003E). The frequency of serious adverse events (SAEs) was comparable between the groups (8.6% vs 9.6%; HR, 1.02; 96% one\u2013sided CI, 1.27).\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\/4\/34\/F2.large.jpg?width=800\u0026amp;height=600\u0026amp;carousel=1\u0022 title=\u0022CV Endpoints \u0026#x2013; Reported SAEs.\u0022 class=\u0022fragment-images colorbox-load\u0022 rel=\u0022gallery-fragment-images-350579121\u0022 data-figure-caption=\u0022CV Endpoints \u0026#x2013; Reported SAEs.\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003E\u003Cimg class=\u0022fragment-image\u0022 alt=\u0022Figure 2.\u0022 src=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/12\/4\/34\/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\/4\/34\/F2.large.jpg?download=true\u0022 class=\u0022highwire-figure-link highwire-figure-link-download\u0022 title=\u0022Download Figure 2.\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\/4\/34\/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\/14011\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 2.\u003C\/span\u003E \n            \u003Cp id=\u0022p-10\u0022 class=\u0022first-child\u0022\u003ECV Endpoints \u2013 Reported SAEs.\u003C\/p\u003E\n         \u003Cq class=\u0022attrib\u0022 id=\u0022attrib-2\u0022\u003EReproduced from Gaziano JM et al. Randomized clinical trial of quick\u2013release bromocriptine among patients with type 2 diabetes on overall safety and cardiovascular outcomes. \u003Cem\u003EDiabetes Care\u003C\/em\u003E 2010. Jul;33(7):1503\u20138. With permission from the American Diabetes Association.\u003C\/q\u003E\u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cp id=\u0022p-11\u0022\u003EIncretin\u2013 and neuroendocrine\u2013based therapies for patients with T2DM are exciting new developments; with the potential to improve overall CVD risk based on experimental and early clinical data. Although these early developments are promising, we await the results of the ongoing large multicenter clinical trials that are designed to determine whether these therapies reduce CV events in patients with T2DM.\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\/4\/34.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?nznhr1\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?nznhr1\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}