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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\u003EA pharmacodynamics study in patients with type 2 diabetes mellitus (T2DM) reveals that sitagliptin QD provides greater inhibition of dipeptidyl peptidase-4 (DPP-4) through the dosing interval (ie, measured at trough, 24 hours following the last morning dose) than either saxagliptin 5 mg QD or vildagliptin 50 mg QD and similar DPP-4 inhibition to vildagliptin 50 mg BID. The findings come from a randomized, placebo-controlled, open-label, crossover study.\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\u003EDiabetes \u0026amp; Endocrinology Clinical Trials\u003C\/li\u003E\u003C\/ul\u003E\u003Cul class=\u0022kwd-group clinical-trial\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003EDiabetes Mellitus\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EDiabetes \u0026amp; Endocrinology Clinical Trials\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\u003EA pharmacodynamics study in patients with type 2 diabetes mellitus (T2DM) reveals that sitagliptin QD provides greater inhibition of dipeptidyl peptidase-4 (DPP-4) through the dosing interval (ie, measured at trough, 24 hours following the last morning dose) than either saxagliptin 5 mg QD or vildagliptin 50 mg QD and similar DPP-4 inhibition to vildagliptin 50 mg BID. The findings come from a randomized, placebo-controlled, open-label, crossover study presented by Harvey L. Katzeff, MD, Merck\/MSD, Whitehouse Station, New Jersey, USA.\u003C\/p\u003E\u003Cp id=\u0022p-3\u0022\u003EBecause the soluble form of DPP-4 is shed into the circulation, measurement of DPP-4 activity in blood is possible. Inhibitors of DPP-4 are heterogeneous in structure and have different pharmacokinetic, pharmacodynamic, and DPP-4-binding characteristics. No direct comparison of DPP-4 inhibition among these agents using a single inhibition assay in the same cohort had been conducted prior to this study. An assay that minimized \u003Cem\u003Eex vivo\u003C\/em\u003E plasma dilution was used to assess trough DPP-4 inhibition after the final dose following 5 days of administration of saxagliptin 5 mg QD, sitagliptin 100 mg QD, and vildagliptin 50 mg QD and BID regimens in a cohort of patients with T2DM (n=22). Trough DPP-4 inhibition for each of the four regimens and placebo control could be directly compared at 24 hours following the final morning dose. Eligible patients were required to have HbA1C levels of 6.5% to 10.0% (inclusive) either while treatment-na\u00efve or after being washed off of prior antihyperglycemic medication.\u003C\/p\u003E\u003Cp id=\u0022p-4\u0022\u003EIn separate treatment periods, each participant received 5 days of either saxagliptin 5 mg QD, sitagliptin 100 mg QD, vildagliptin 50 mg QD, vildagliptin 50 mg BID, or placebo. Each participant was assigned to a randomized treatment sequence according to a computer-generated allocation schedule. Treatment periods were separated by at least 10 days. The randomized cohort included 12 women and 10 men with a mean HbA1C of 7.4% and mean age of 55 years.\u003C\/p\u003E\u003Cp id=\u0022p-5\u0022\u003EThe percent DPP-4 inhibition was calculated for each treatment relative to the predose DPP-4 activity in each period. Sitagliptin QD and vildagliptin BID achieved \u0026gt;90% trough DPP-4 inhibition, reaching steady state within 1 day. In contrast, trough DPP-4 inhibition was 73.5% after saxagliptin QD and 28.8% after vildagliptin QD. The trough DPP-4 inhibition following placebo treatment was within 3.9% of the baseline measure (\u003Ca id=\u0022xref-fig-1-1\u0022 class=\u0022xref-fig\u0022 href=\u0022#F1\u0022\u003EFigure 1\u003C\/a\u003E). \u201cDPP-4 inhibition \u226580% is believed to be necessary to achieve maximal efficacy of DPP-4 inhibitors\u201d, said Dr. Katzeff.\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\/13\/17\/22.2\/F1.large.jpg?width=800\u0026amp;height=600\u0026amp;carousel=1\u0022 title=\u0022Trough % Inhibition of DPP-4 Activity Over 5 Days\u0022 class=\u0022fragment-images colorbox-load\u0022 rel=\u0022gallery-fragment-images-1930423953\u0022 data-figure-caption=\u0022Trough % Inhibition of DPP-4 Activity Over 5 Days\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\/13\/17\/22.2\/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\/13\/17\/22.2\/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\/13\/17\/22.2\/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\/13801\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-6\u0022 class=\u0022first-child\u0022\u003ETrough % Inhibition of DPP-4 Activity Over 5 Days\u003C\/p\u003E\n         \u003Cq class=\u0022attrib\u0022 id=\u0022attrib-1\u0022\u003EDPP-4=dipeptidyl peptidase-4; PBO=placebo.\u003C\/q\u003E\u003Cq class=\u0022attrib\u0022 id=\u0022attrib-2\u0022\u003EReproduced with permission from HL Katzeff, MD.\u003C\/q\u003E\u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cp id=\u0022p-7\u0022\u003EThe time course of DPP-4 inhibition over 96 hours and following 5 days of administration favored sitagliptin 100 mg QD (\u003Ca id=\u0022xref-fig-2-1\u0022 class=\u0022xref-fig\u0022 href=\u0022#F2\u0022\u003EFigure 2\u003C\/a\u003E), which maintained DPP-4 inhibition of \u223c92% over 24 hours that declined slowly over the following 24 to 96 hours. Vildagliptin 50 mg BID maintained \u0026gt;90% DPP-4 inhibition over 24 hours but inhibition declined rapidly over the following 12 to 24 hours. Saxagliptin 5 mg QD maintained \u223c72% DPP-4 inhibition at 24 hours but inhibition also declined rapidly over the following 12 to 24 hours. Vildagliptin 50 mg QD achieved rapid DPP-4 inhibition but inhibition declined rapidly starting at 12 hours.\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\/13\/17\/22.2\/F2.large.jpg?width=800\u0026amp;height=600\u0026amp;carousel=1\u0022 title=\u0022Percent Inhibition of DPP-4 Activity at 0\u0026#x2013;96 Hours\u0022 class=\u0022fragment-images colorbox-load\u0022 rel=\u0022gallery-fragment-images-1930423953\u0022 data-figure-caption=\u0022Percent Inhibition of DPP-4 Activity at 0\u0026#x2013;96 Hours\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\/13\/17\/22.2\/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\/13\/17\/22.2\/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\/13\/17\/22.2\/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\/13802\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-8\u0022 class=\u0022first-child\u0022\u003EPercent Inhibition of DPP-4 Activity at 0\u201396 Hours\u003C\/p\u003E\n         \u003Cq class=\u0022attrib\u0022 id=\u0022attrib-3\u0022\u003EDPP-4=dipeptidyl peptidase-4; PBO=placebo.\u003C\/q\u003E\u003Cq class=\u0022attrib\u0022 id=\u0022attrib-4\u0022\u003EReproduced with permission from HL Katzeff, MD.\u003C\/q\u003E\u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cp id=\u0022p-9\u0022\u003ETen adverse events were reported in 7 of the 22 patients, with headache the most commonly reported adverse event (6 events reported in 3 patients). All adverse events were mild or moderate in intensity and were transient in nature. There were no adverse events that led to patient withdrawal from the study.\u003C\/p\u003E\u003Cp id=\u0022p-10\u0022\u003EDr. Katzeff concluded that the three DPP-4 inhibitors studied provided significantly different trough levels of DPP-4 inhibition. Trough inhibition was submaximal in patients treated with saxagliptin 5 mg QD and vildagliptin 50 mg QD, whereas \u0026gt;90% DPP-4 inhibition was sustained throughout 24 hours in patients treated with sitagliptin 100 mg QD and vildagliptin 50 mg BID.\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\/22.2.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?nznlgd\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?nznlgd\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}