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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 incretin mimemics\u2014dipeptidyl peptidase-4 (DPP-4) inhibitors and the glucagon-like peptide-1 (GLP-1) receptor agonists\u2014stimulate insulin secretion and inhibit glucagon secretion to stabilize serum glucose levels. They provide blood glucose reductions that are similar to other antidiabetic drugs, with no associated weight gain and, in the case of the GLP-1 agonists, some weight loss [Drucker DJ, Nauck MA. \u003Cem\u003ELancet\u003C\/em\u003E 2006; Russell-Jones D. \u003Cem\u003EInt J Clin Pract\u003C\/em\u003E 2010].\u003C\/p\u003E\n         \u003C\/div\u003E\u003Cul class=\u0022kwd-group\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003EDiabetes Mellitus\u003C\/li\u003E\u003C\/ul\u003E\u003Cp id=\u0022p-2\u0022\u003EThe incretin mimemics\u2014dipeptidyl peptidase-4 (DPP-4) inhibitors and the glucagon-like peptide-1 (GLP-1) receptor agonists\u2014stimulate insulin secretion and inhibit glucagon secretion to stabilize serum glucose levels. They provide blood glucose reductions that are similar to other antidiabetic drugs, with no associated weight gain and, in the case of the GLP-1 agonists, some weight loss [Drucker DJ, Nauck MA. \u003Cem\u003ELancet\u003C\/em\u003E 2006; Russell-Jones D. \u003Cem\u003EInt J Clin Pract\u003C\/em\u003E 2010].\u003C\/p\u003E\u003Cp id=\u0022p-3\u0022\u003EThere is also some evidence from animal and human models that these compounds may provide \u03b2-cell preservation. In animal studies, they have been shown to increase neogenesis from islet precursor cells, induce \u03b2-cell replication from mature \u03b2-cells, prevent apoptosis in toxic environments, determine insulin biosynthesis that results in greater \u03b2-cell mass, improve \u03b2-cell functional status, and increase recruitment of dormant cells that do not respond to high glucose levels, thus increasing the actively recruiting \u03b2-cell mass [Brubaker PL, Drucker DJ. \u003Cem\u003EEndocrinology\u003C\/em\u003E 2004; Holz GG, Kuhtreiber WM, Habener JF. \u003Cem\u003ENature\u003C\/em\u003E 1993].\u003C\/p\u003E\u003Cp id=\u0022p-4\u0022\u003EIn human studies, patients who received the DPP-4 inhibitor sitagliptin demonstrated a reduced proinsulin: insulin ratio, indicating greater processing of proinsulin to insulin and evidence of healthier \u03b2-cells [Riche DM et al. \u003Cem\u003EAm J Med Sci\u003C\/em\u003E 2009].\u003C\/p\u003E\u003Cp id=\u0022p-5\u0022\u003EIn addition, 3-year results in patients who received exenatide or glargine insulin found increased insulin sensitivity in the exenatide patients over baseline but no change from baseline in the insulin group. Whether the weight loss from exenatide or some other mechanism of action is responsible for the improved insulin sensitivity remains to be determined [Bunck MC. Abstract #848, EASD 2010. Stockholm, Sweden].\u003C\/p\u003E\u003Cdiv class=\u0022section\u0022 id=\u0022sec-1\u0022\u003E\n         \u003Ch2 class=\u0022\u0022\u003EPancreatitis and Incretin Mimetics\u003C\/h2\u003E\n         \u003Cp id=\u0022p-6\u0022\u003EA concern has been raised about the risk of severe pancreatitis in patients who take exenatide. These cases were reported as part of postmarketing surveys, although none were seen during clinical trials.\u003C\/p\u003E\n         \u003Cp id=\u0022p-7\u0022\u003EStudies have found that pancreatitis is significantly more prevalent in people with diabetes, with the risk related to traditional risk factors for the disease, including alcohol intake, obesity, hypertriglyceridemia, gallstones, and the use of certain antihypertensive drugs. An evaluation of a claims-based database that contained more than 40,000 individuals who received either exenatide or sitagliptin, matched against an equal number of patients who received metformin or glyburide initiators, found a relative risk of 1.0 (95% CI, 0.6 to 1.7, exenatide; 95% CI, 0.5 to 2.0, sitagliptin), providing no evidence of a direct association between the drugs and pancreatitis [Dore DD et al. \u003Cem\u003ECurr Med Res Opin\u003C\/em\u003E 2009].\u003C\/p\u003E\n      \u003C\/div\u003E\u003Cdiv class=\u0022section\u0022 id=\u0022sec-2\u0022\u003E\n         \u003Ch2 class=\u0022\u0022\u003EIncretin Mimemics and C-Cell Abnormalities\u003C\/h2\u003E\n         \u003Cp id=\u0022p-8\u0022\u003EConcern has also been raised about the drug liraglutide, after animal studies found a slightly higher risk of C-cell abnormalities and C-cell medullary thyroid carcinoma, a cancer that is very rare in humans. However, further studies found significant differences in C-cell response to GLP-1 receptor agonist stimulation compared with human C-cell response. Specifically, rat C-cells demonstrated far greater calcitonin release and adenylate cyclase activation than human cells, in which no immediate response was seen after GLP-1 receptor activation [Knudsen B et al. \u003Cem\u003EEndocrinology\u003C\/em\u003E 2010]. No cases of medullary thyroid carcinoma have been reported in humans who have taken liraglutide, and it is unlikely that any direct association between this rare form of cancer and the GLP-1 receptor agonist will be found.\u003C\/p\u003E\n      \u003C\/div\u003E\u003Cdiv class=\u0022section\u0022 id=\u0022sec-3\u0022\u003E\n         \u003Ch2 class=\u0022\u0022\u003EIncretin Mimetics and Cardiovascular Effects\u003C\/h2\u003E\n         \u003Cp id=\u0022p-9\u0022\u003EStudies that have been conducted in dogs, rats, and pigs using exenatide and liraglutide have found far smaller areas of necrotic tissue following induced myocardial infarction (MI) on animals who received exenatide or liraglutide at the time of MI [Timmers L et al. \u003Cem\u003EJ Am Coll Cardiol\u003C\/em\u003E 2009; Sauve M et al. \u003Cem\u003EDiabetes\u003C\/em\u003E 2008; Bose AK et al. \u003Cem\u003EDiabetes\u003C\/em\u003E 2005].\u003C\/p\u003E\n         \u003Cp id=\u0022p-10\u0022\u003EAlthough large human studies are pending, a small pilot study, involving 5 patients with type 2 diabetes and 5 without who arrived in the emergency department with acute MI and low left ventricular ejection fraction, found that those who were randomized to a 72-hour infusion of a GLP-1 receptor agonist demonstrated significantly improved left ventricular ejection fraction, global wall motion score indexes, and regional wall motion score indexes compared with controls (p\u0026lt;0.01 for all) [Nikolaidis LA et al. \u003Cem\u003ECirculation\u003C\/em\u003E 2004].\u003C\/p\u003E\n         \u003Cp id=\u0022p-11\u0022\u003EThere is also some evidence that the DPP-4 inhibitors may significantly reduce cardiovascular events in patients with diabetes compared with sulfonylureas [Filozof C \u0026amp; Gautier JF. \u003Cem\u003EDiabet Med\u003C\/em\u003E 2010; Ferrannini E et al. \u003Cem\u003EDiabetes Obes Metab\u003C\/em\u003E 2009]. This conclusion, however, is based on small numbers of events in studies that aimed at demonstrating improved glycemic control. Larger trials are needed to better characterize the benefits and risks of incretin-based antidiabetic medications with regard to cardiovascular outcome.\u003C\/p\u003E\n      \u003C\/div\u003E\u003Cul class=\u0022copyright-statement\u0022\u003E\u003Cli class=\u0022fn\u0022 id=\u0022copyright-statement-1\u0022\u003E\u00a9 2010 MD Conference Express\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\/10\/9\/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_openurl.js?nzmocp\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}