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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\u003ELX4211, a dual inhibitor of sodium glucose transporters 1 and 2 (SGLT1\/2), demonstrated a clear dose reduction in plasma glucose concentration (HbA1C) in patients with type 2 diabetes mellitus (T2DM) inadequately controlled on metformin monotherapy in the Safety and Efficacy of LX4211 with Metformin in T2DM Patients with Inadequate Glycemic Control on Metformin study. SGLT1 is primarily responsible for gastrointestinal glucose absorption, while SGLT2 is primarily responsible for renal glucose reabsorption, leading to reductions in blood glucose levels and weight loss.\u003C\/p\u003E\n         \u003C\/div\u003E\u003Cul class=\u0022kwd-group\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003EHypertensive Disease\u003C\/li\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\u003ECardiology Clinical Trials\u003C\/li\u003E\u003C\/ul\u003E\u003Cp id=\u0022p-2\u0022\u003ELX4211, a dual inhibitor of sodium glucose transporters 1 and 2 (SGLT1\/2), demonstrated a clear dose reduction in plasma glucose concentration (HbA1C) in patients with type 2 diabetes mellitus (T2DM) inadequately controlled on metformin monotherapy in the Safety and Efficacy of LX4211 with Metformin in T2DM Patients with Inadequate Glycemic Control on Metformin study. SGLT1 is primarily responsible for gastrointestinal (GI) glucose absorption, while SGLT2 is primarily responsible for renal glucose reabsorption, leading to reductions in blood glucose levels and weight loss. Julio Rosenstock, MD, Dallas Diabetes and Endocrine Center, Dallas, Texas, USA, who presented this study believes that LX4211 has the potential to address multiple cardiovascular disease risk factors in diabetic patients.\u003C\/p\u003E\u003Cp id=\u0022p-3\u0022\u003EThe study was designed to evaluate the dose-range efficacy and safety of LX4211 versus placebo from baseline to Week 12 in patients with T2DM inadequately controlled on metformin monotherapy. Additional eligibility criteria included being aged 18 to 75 years with a body mass index \u226445 kg\/m\u003Csup\u003E2\u003C\/sup\u003E, and HbA1C \u22657% to \u226410.5%. After 2 weeks of screening, subjects were randomly assigned to treatment with placebo or 1 of 4 LX4211 dosages (75 mg QD, 200 mg QD, 200 mg BID, or 400 mg QD) for 12 weeks and followed for an additional 2 weeks. The primary study endpoint was the change in HbA1C from baseline to Week 12. Secondary outcomes included percentage of patients reaching target HbA1C of \u22647% at Week 12, fasting plasma glucose change from baseline to Week 12, body weight change, blood pressure (BP) change, urinary glucose change, and safety.\u003C\/p\u003E\u003Cp id=\u0022p-4\u0022\u003ERandomized patients (n=299) were mean age 56 years, 42% female, and had a BMI of 32 to 34 kg\/m\u003Csup\u003E2\u003C\/sup\u003E, and HbA1C of 7.9% to 8.3 %. Patients had normal blood pressure (BP) and lipid levels. All doses of LX411 significantly reduced HbA1C compared with baseline, with dose related changes from 0.4% to 0.9%. Baseline characteristics were balanced between randomization groups.\u003C\/p\u003E\u003Cp id=\u0022p-5\u0022\u003ERelative to placebo after 12 weeks of treatment; LX411 reduced HbA1C beginning at Week 1 and continuing out to Week 12 (p\u0026lt;0.001 for the 200-mg BID and 400-mg QD doses; p\u0026lt;0.05 for 75-mg and 200-mg QD doses;). Maximum effect on urinary glucose excretion was achieved with 200 mg QD at Weeks 4, 8, and 12. No further glucose excretion was achieved with the 200-mg BID or 400-mg QD doses. However, further reductions in HbA1C were evident with the higher doses of LX411, which probably indicates further inhibition of SGLT1. Weight loss was achieved with all doses except for the 75-mg dose, up to 2.5 kg at Week 12 with 200 mg BID (p\u0026lt;0.001). Compared with placebo, systolic BP was significantly (p\u0026lt;0.05) reduced with the 200-mg BID and 400-mg QD doses over the 12-week period. Diastolic BP was not significantly changed. No clinically meaningful changes in high- or low-density lipoprotein cholesterol levels over baseline or compared with placebo were evident.\u003C\/p\u003E\u003Cp id=\u0022p-6\u0022\u003EAdverse events (AEs) were well balanced across the treatment arms and similar in frequency to those seen with placebo. Common AEs associated with LX4211 were vaginal infections (3% to 5%), GI disorders, and headaches. There were no dose-related differences in drug discontinuation due to AEs.\u003C\/p\u003E\u003Cp id=\u0022p-7\u0022\u003EIn poorly controlled patients with T2DM on metformin, dual SGLT 1 and 2 inhibition with LX2411 improved glucose control and was associated with consistent reductions in systolic BP and body weight without an increase in hypoglycemia. Dr. Rosenstock concluded that, because of its insulin-independent effects, LX4211 can potentially address multiple cardiovascular risk factors in patients with T2DM and it warrants further study.\u003C\/p\u003E\u003Cp id=\u0022p-8\u0022\u003EAll novel oral glycemic agents are now required to undergo Phase 3 study evaluations to determine whether they affect clinical cardiovascular endpoints, including heart failure and ischemic events. In addition, these Phase 3 trials are often longer than the initial studies investigating glucose control and are helpful to evaluate, serious AEs, such as hypoglycemia, hypotension, or off-target effects. With this particular class of diabetic agents, an increase in genitourinary infections may be plausible since glycosuria is increased with this therapy.\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\/18\/26\/F1.large.jpg?width=800\u0026amp;height=600\u0026amp;carousel=1\u0022 title=\u0022The editors would like to thank the many members of the AHA Scientific Sessions 2012 presenting faculty who generously gave their time to ensure the accuracy and quality of the articles in this publication.\u0022 class=\u0022fragment-images colorbox-load\u0022 rel=\u0022gallery-fragment-images-1908428480\u0022 data-figure-caption=\u0022The editors would like to thank the many members of the AHA Scientific Sessions 2012 presenting faculty who generously gave their time to ensure the accuracy and quality of the articles in this publication.\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\/12\/18\/26\/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\/18\/26\/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\/12\/18\/26\/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\/13073\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\u0022 xmlns:xhtml=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022\u003E\n            \u003Cp id=\u0022p-9\u0022 class=\u0022first-child\u0022\u003EThe editors would like to thank the many members of the AHA Scientific Sessions 2012 presenting faculty who generously gave their time to ensure the accuracy and quality of the articles in this publication.\u003C\/p\u003E\n         \u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\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\/18\/26.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?nzn6n1\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?nzn6n1\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}