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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\u003EGlucagon-like peptide-1 (GLP-1) is an incretin hormone that regulates postprandial insulin secretion. The incretin effect is believed to be critical for maintenance of normal plasma glucose and glucose tolerance [\u003Cem\u003EDiab\u003C\/em\u003E 1995]. Experiments using antagonists of the GLP-1 receptor show that GLP-1 is responsible for a substantial part of the insulin response to oral glucose [\u003Cem\u003EDiab\u003C\/em\u003E 1995; \u003Cem\u003EDiab\u003C\/em\u003E 1994]. This article discusses GLP-1 receptor agonists and DPP IV inhibitors.\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\u003Ehyperglycemia\/hypoglycemia\u003C\/li\u003E\u003C\/ul\u003E\u003Cdiv class=\u0022section\u0022 id=\u0022sec-1\u0022\u003E\n         \n         \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\/6\/2\/9\/F1.large.jpg?width=800\u0026amp;height=600\u0026amp;carousel=1\u0022 title=\u0022\u0022 class=\u0022fragment-images colorbox-load\u0022 rel=\u0022gallery-fragment-images-1067356234\u0022 data-figure-caption=\u0022\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003E\u003Cimg class=\u0022fragment-image\u0022 alt=\u0022Figure1\u0022 src=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/6\/2\/9\/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\/6\/2\/9\/F1.large.jpg?download=true\u0022 class=\u0022highwire-figure-link highwire-figure-link-download\u0022 title=\u0022Download Figure1\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\/6\/2\/9\/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\/10845\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\n         \u003Cp id=\u0022p-2\u0022\u003EGlucagon-like peptide-1 (GLP-1) is an incretin hormone that regulates postprandial insulin secretion. The incretin effect is believed to be critical for maintenance of normal plasma glucose and glucose tolerance (\u0026lt;\u003Cem\u003EDiab\u003C\/em\u003E 1995). Experiments using antagonists of the GLP-1 receptor show that GLP-1 is responsible for a substantial part of the insulin response to oral glucose (\u003Cem\u003EDiab\u003C\/em\u003E 1995) (\u003Cem\u003EDiab\u003C\/em\u003E 1994).\u003C\/p\u003E\n         \u003Cp id=\u0022p-3\u0022\u003EGLP-1\u0027s physiological effects, as explained by Jens Juul Hoist, MD, PhD, University of Copenhagen, Denmark, are that it causes glucose dependent insulin secretion, inhibits glucagon secretion, delays gastric emptying and increases satiety GLP-1 may also cause beta cell growth (shown \u003Cem\u003Ein vitro\u003C\/em\u003E and in animal studies), have neuroprotective effects, and have favorable cardiovascular effects, he said, but these are not known yet for sure (Vilsb\u00f8ll et al, \u003Cem\u003ERegulatory Peptides\u003C\/em\u003E 2003).\u003C\/p\u003E\n         \u003Cp id=\u0022p-4\u0022\u003EOnly 10 to 15 percent of secreted GLP-1 reaches the pancreas intact, but GLP-1 action may involve the central nervous system as well. GLP-1 secretion must be measured as the sum of active GLP-1 and its metabolite GLP-1 (9\u201336) arnica. A study cited in \u003Cem\u003ENature\u003C\/em\u003E magazine (1996) stated that ICV administration of GLP-1 inhibits food intake in rats.\u003C\/p\u003E\n      \u003C\/div\u003E\u003Cdiv class=\u0022section\u0022 id=\u0022sec-2\u0022\u003E\n         \u003Ch2 class=\u0022\u0022\u003EExendin-4: More Than Just a GLP-1 Receptor Agonist?\u003C\/h2\u003E\n         \u003Cp id=\u0022p-5\u0022\u003EExendin-4 (exenatide), taken from the saliva of the Gila monster, is 53 percent homologous with GLP-1 and acts as an agonist at the GLP-1 receptor. It is also insensitive to DPP-4, the enzyme that degrades GLP-1.\u003C\/p\u003E\n         \u003Cp id=\u0022p-6\u0022\u003E\u201cExendin-4 provides has several mechanisms of action: it causes glucose dependent insulin secretion, suppresses postprandial hyperglucagonemia, delays gastric emptying, contributes to weight loss and may decreases insulin resistance and restore beta cell function,\u201d explained Dr. Vahl.\u003C\/p\u003E\n         \u003Cp id=\u0022p-7\u0022\u003EDr. Vahl also pointed out that other studies have shown that continuous subcutaneous infusion of GLP-1 for 6 weeks improves fasting and postprandial hyperglycemia (PPHG) in Type 2 diabetes, reduces HbA1C level by 1.3%, and reduces body weight. Kendall et al (ADA 2005) noted progressive body weight reduction in exenatide-treated patients, and DeFronzo (\u003Cem\u003EDiab Care\u003C\/em\u003E 2005) and Buse (\u003Cem\u003EDiab Care\u003C\/em\u003E 2005) also found that Exendin-4 decreased body weight and restored first phase insulin secretion (\u003Cem\u003EJCEM\u003C\/em\u003E 2005).\u003C\/p\u003E\n         \u003Cp id=\u0022p-8\u0022\u003EHenry (ADA 2006) and his colleagues studied change in body weight for a 2-year completer population in an open-label uncontrolled study. Over 2 years, weight reduction from baseline was \u22124.7\u00b10.3 kg and treatment with exendin-4 led to sustained improvement in glycemic control. Linnebjerg (ADA 2006) showed that exenatide slowed gastric emptying in a dose dependent fashion.\u003C\/p\u003E\n         \u003Cp id=\u0022p-9\u0022\u003EAnother exciting development is exenatide\u0027s long-acting release (LAR) technology, which utilizes biodegradable polymeric microspheres for extended drug release. Liraglutide is the long action form of exenatide. Exenatide\u0027s plasma concentration is detectable weeks to months after a single dose of liraglutide, according to Dr. Nauck. Liraglutide has been shown to reduce systemic blood pressure (Vilsboll ADA 2006), triglycerides, PAI-1 and BNP concentrations in patients with Type 2 diabetes, though these observed effects need to be explored further. It also seems to offer weight reduction comparable to sibutramine and rimonabant.\u003C\/p\u003E\n      \u003C\/div\u003E\u003Cdiv class=\u0022section\u0022 id=\u0022sec-3\u0022\u003E\n         \u003Ch2 class=\u0022\u0022\u003ENew Directions in Incretin Therapy: DPP IV inhibitors\u003C\/h2\u003E\n         \u003Cp id=\u0022p-10\u0022\u003EAdditional therapies on the horizon that utilize the incretin system include DPP-4 inhibitors. These are oral medications that block DPP IV, the enzyme that degrades GLP-1. Their mechanism of action is through GLP-1 receptors, possibly GIP receptors, and other receptors as well. Dr. Nauck summarized the potentials of vildagliptin and sitagliptin, two DPP IV inhibitors under active investigation.\u003C\/p\u003E\n         \u003Cp id=\u0022p-11\u0022\u003EVildagliptin may suppress endogenous glucose production. Dr. Nauck pointed out that vildagliptin also contributes to restoration of the acute phase insulin response, has been associated with a lowering of blood pressure, and reduces postprandial hypertriglyceridemia. It may be used as adjuvant therapy in patients who use insulin. Sitagliptin may be used in patients with renal insufficiency, but it has been found to have pharmacokinetic interactions with glyburide and rosiglitazone, he noted.\u003C\/p\u003E\n         \u003Cp id=\u0022p-12\u0022\u003EIncretin mimetics cause a \u2014 3 to 5 kg weight change depending on dose and duration of action while DPP-4 inhibitors have been associated with less dramatic weight loss. Studies have shown that DPP IV inhibitors are associated with less nausea and hypoglycemia compared to incretin mimetics.\u003C\/p\u003E\n         \u003Cp id=\u0022p-13\u0022\u003EThe addition of these exciting new pharmacological agents will enhance our ability to treat and hopefully one day to conquer diabetes worldwide.\u003C\/p\u003E\n         \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\/6\/2\/9\/F2.large.jpg?width=800\u0026amp;height=600\u0026amp;carousel=1\u0022 title=\u0022\u0022 class=\u0022fragment-images colorbox-load\u0022 rel=\u0022gallery-fragment-images-1067356234\u0022 data-figure-caption=\u0022\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003E\u003Cimg class=\u0022fragment-image\u0022 alt=\u0022Figure2\u0022 src=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/6\/2\/9\/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\/6\/2\/9\/F2.large.jpg?download=true\u0022 class=\u0022highwire-figure-link highwire-figure-link-download\u0022 title=\u0022Download Figure2\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\/6\/2\/9\/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\/10847\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\n      \u003C\/div\u003E\u003Cul class=\u0022copyright-statement\u0022\u003E\u003Cli class=\u0022fn\u0022 id=\u0022copyright-statement-1\u0022\u003E\u00a9 2006 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\/6\/2\/9.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?nzlz4d\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?nzlz4d\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}