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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\u003EWhile good glycemic control is associated with preventing microvascular complications, its association with cardiovascular disease is far less straightforward. Key studies have yet to report a consistently positive effect of intensive glucose lowering on cardiovascular outcomes. For now, intensive glucose control should not be considered a strategy to prevent macrovascular complications.\u003C\/p\u003E\n         \u003C\/div\u003E\u003Cul class=\u0022kwd-group\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003Ehyperglycemia\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Ecardiovascular\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Etype 2 diabetes mellitus\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Emacrovascular\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Emicrovascular\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Ecardiology \u0026amp; cardiovascular medicine clinical trials\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Eendocrinology, diabetes \u0026amp; metabolism clinical trials\u003C\/li\u003E\u003C\/ul\u003E\u003Cdiv class=\u0022section\u0022 id=\u0022sec-1\u0022\u003E\n         \n         \u003Cp id=\u0022p-2\u0022\u003ESilvio E. Inzucchi, MD, Yale University School of Medicine, New Haven, Connecticut, USA, presented the second of 2 Presidential Plenary sessions and focused on evolving views of glucose control and its effect on cardiovascular (CV) outcomes.\u003C\/p\u003E\n         \u003Cp id=\u0022p-3\u0022\u003EHe began the session by reviewing the epidemiologic and pathophysiologic links between HbA\u003Csub\u003E1c\u003C\/sub\u003E and microvascular complications, as noted in the UKPDS 35 trial [Stratton IM et al. \u003Cem\u003EBMJ\u003C\/em\u003E. 2000]. However, a definitive link between HbA\u003Csub\u003E1c\u003C\/sub\u003E and myocardial infarction (MI) and mortality remains more elusive and controversial [Emerging Risk Factors Collaboration. \u003Cem\u003EJAMA\u003C\/em\u003E. 2014; Brewer N et al. \u003Cem\u003EDiabetes Care\u003C\/em\u003E. 2008].\u003C\/p\u003E\n         \u003Cp id=\u0022p-4\u0022\u003EAccording to Dr Inzucchi, this lack of an association is probably due to the fact that atherosclerosis occurs at the macrovascular level, which is influenced by a variety of factors, including genetics, blood lipids, inflammation, obesity, blood pressure (BP), and smoking, as well as hyperglycemia and probably insulin resistance. Microvascular complications, however, occur in a single epithelial layer within the capillaries, where the predominant risk factors are hyperglycemia, BP, and genetics.\u003C\/p\u003E\n         \u003Cp id=\u0022p-5\u0022\u003EDr Inzucchi went on to highlight results from the 5 major clinical trials that have investigated the impact of intensive therapy for diabetes on CV outcomes: (1) UKPDS 33 [UK Prospective Diabetes Study. \u003Cem\u003ELancet\u003C\/em\u003E. 1998], (2) DCCT\/EDIC [Holman RR et al. \u003Cem\u003EN Engl J Med\u003C\/em\u003E. 2008; The Diabetes Control and Complications Trial Research Group. \u003Cem\u003EN Engl J Med\u003C\/em\u003E. 1993], (3) ACCORD [Action to Control Cardiovascular Risk in Diabetes Study Group. \u003Cem\u003EN Engl J Med\u003C\/em\u003E. 2008], (4) ADVANCE [Advance Collaborative Group. \u003Cem\u003EN Engl J Med\u003C\/em\u003E. 2008], and (5) VADT [Duckworth W et al. \u003Cem\u003EN Engl J Med\u003C\/em\u003E. 2009].\u003C\/p\u003E\n         \u003Cp id=\u0022p-6\u0022\u003EDr Inzucchi emphasized that among all these aforementioned studies, microvascular complications were improved, but a neutral effect was seen on mortality and CV events. The exceptions are the trials with long-term components (UKPDS and DCCT\/EDIC), where there was an improvement in both mortality and CV events, and the ACCORD trial, where there was an increase in mortality. Dr Inzucchi cautioned that the increase in mortality seen in ACCORD was likely driven by an older group of patients with a high risk of overt atherosclerosis at baseline. Further, data from the VADT study suggested that intensive glucose lowering reduced CV events only in those with no or little preexisting atherosclerosis in coronary arteries [Reaven PD et al. \u003Cem\u003EDiabetes\u003C\/em\u003E. 2009]. Aside from these 5 trials, the ORIGIN Trial [ORIGIN Trial Investigators. \u003Cem\u003EN Engl J Med\u003C\/em\u003E. 2012] showed that insulin glargine had a neutral effect on CV outcomes in patients with only mild hyperglycemia over a median follow-up of 6.2 years. Dr Inzucchi also observed that, based on meta-analyses, if there is a CV benefit from glucose lowering, it is on the order of a 15% relative risk reduction.\u003C\/p\u003E\n         \u003Cp id=\u0022p-7\u0022\u003EDr Inzucchi then moved on to discuss CV issues associated with various therapies for type 2 diabetes mellitus (T2DM; \u003Ca id=\u0022xref-table-wrap-1-1\u0022 class=\u0022xref-table\u0022 href=\u0022#T1\u0022\u003ETable 1\u003C\/a\u003E). Metformin probably provides some CV advantage over diet and possibly sulfonylurea drugs. The TZD pioglitazone appeared to reduce major adverse CV events in 1 trial, but these data need to be confirmed. This specific class of insulin-sensitizing drugs remains highly controversial.\u003C\/p\u003E\n         \u003Cdiv id=\u0022T1\u0022 class=\u0022table pos-float\u0022\u003E\u003Cdiv class=\u0022table-inline\u0022\u003E\u003Cdiv class=\u0022callout\u0022\u003E\u003Cspan\u003EView this table:\u003C\/span\u003E\u003Cul class=\u0022callout-links\u0022\u003E\u003Cli class=\u00220 first\u0022\u003E\u003Ca href=\u0022\/\u0022 class=\u0022table-expand-inline\u0022 data-table-url=\u0022\/highwire\/markup\/16533\/expansion?postprocessors=highwire_figures%2Chighwire_math%2Chighwire_inline_linked_media%2Chighwire_embed\u0026amp;table-expand-inline=1\u0022 html=\u00221\u0022 fragment=\u0022#\u0022 external=\u00221\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView inline\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00221\u0022\u003E\u003Ca href=\u0022\/highwire\/markup\/16533\/expansion?width=1000\u0026amp;height=500\u0026amp;iframe=true\u0026amp;postprocessors=highwire_figures%2Chighwire_math%2Chighwire_inline_linked_media\u0022 class=\u0022colorbox colorbox-load table-expand-popup\u0022 rel=\u0022gallery-fragment-tables\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView popup\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00222 last\u0022\u003E\u003Ca href=\u0022\/highwire\/powerpoint\/16533\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\u003Cdiv class=\u0022table-caption\u0022\u003E\u003Cspan class=\u0022table-label\u0022\u003ETable 1.\u003C\/span\u003E \n               \u003Cp id=\u0022p-8\u0022 class=\u0022first-child\u0022\u003ECardiovascular Issues Associated With Therapies for T2DM\u003C\/p\u003E\n            \u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\n         \u003Cp id=\u0022p-11\u0022\u003EIn 2008, the US Food and Drug Administration (FDA) issued an industry guidance that mandated manufacturers of diabetes medications to demonstrate that their therapy would not result in an unacceptable increase in CV risk [US Department of Health and Human Services. \u003Cem\u003EGuidance for Industry\u003C\/em\u003E. 2008]. This guidance was issued as a direct result of the controversy surrounding rosiglitazone and its purported association with poor CV outcomes. Dr Inzucchi reviewed the main points of the guidance, which mandates that manufacturers implement additional pre- and postmarketing CV outcome trials (CVOTs), using the following metrics:\u003C\/p\u003E\n         \u003Cul class=\u0022list-unord \u0022 id=\u0022list-1\u0022\u003E\u003Cli id=\u0022list-item-1\u0022\u003E\n               \u003Cp id=\u0022p-12\u0022\u003EPremarketing analyses: HR for major adverse CV events (MACEs) to include an upper limit of the 95% CI\u2005\u0026lt;\u20051.8\u003C\/p\u003E\n            \u003C\/li\u003E\u003Cli id=\u0022list-item-2\u0022\u003E\n               \u003Cp id=\u0022p-13\u0022\u003EPostmarketing analyses: HR for MACEs to include an upper limit of the 95% CI\u2005\u0026lt;\u20051.3\u003C\/p\u003E\n            \u003C\/li\u003E\u003Cli id=\u0022list-item-3\u0022\u003E\n               \u003Cp id=\u0022p-14\u0022\u003EMeta-analysis strategy using phase 2\/3 data\u003C\/p\u003E\n            \u003C\/li\u003E\u003Cli id=\u0022list-item-4\u0022\u003E\n               \u003Cp id=\u0022p-15\u0022\u003EBlinded central adjudication of CV events in phase 2\/3\u003C\/p\u003E\n            \u003C\/li\u003E\u003Cli id=\u0022list-item-5\u0022\u003E\n               \u003Cp id=\u0022p-16\u0022\u003EInclusion of high-risk patients\u003C\/p\u003E\n            \u003C\/li\u003E\u003Cli id=\u0022list-item-6\u0022\u003E\n               \u003Cp id=\u0022p-17\u0022\u003EMinimum exposure of 2 years\u003C\/p\u003E\n            \u003C\/li\u003E\u003Cli id=\u0022list-item-7\u0022\u003E\n               \u003Cp id=\u0022p-18\u0022\u003EApproximately 15\u2005000 patient years\u003C\/p\u003E\n            \u003C\/li\u003E\u003C\/ul\u003E\n         \u003Cp id=\u0022p-19\u0022\u003EDr Inzucchi then discussed the published results from 2 of these CVOTs\u2014SAVOR-TIMI 53 [Scirica BM et al. \u003Cem\u003EN Engl J Med\u003C\/em\u003E. 2013] and EXAMINE [White WB et al. \u003Cem\u003EN Engl J Med\u003C\/em\u003E. 2013]. SAVOR-TIMI 53 followed \u0026gt;\u200516\u2005000 patients who had been randomized to either saxagliptin or placebo over a median of 2.1 years with a primary end point of cardiovascular death, nonfatal myocardial infarction or nonfatal ischemic stroke (saxagliptin, n\u2005=\u2005613; placebo, n\u2005=\u2005609). Although there was neither an increase nor a decrease in ischemic results among patients in the saxagliptin arm, the rate of hospitalization for heart failure was significantly increased (\u003Cem\u003EP\u2005\u003C\/em\u003E=\u2005.007). In the EXAMINE trial, 5380 patients who had T2DM and were hospitalized for either an MI or unstable angina were randomly assigned to alogliptin (n\u2005=\u20052701) or placebo (n\u2005=\u20052679). Patients were followed for up to 40 months (median, 18 months). There was no significant difference between the groups in mortality from CV causes, nonfatal MI, and nonfatal stroke (\u003Cem\u003EP\u003C\/em\u003E\n            \u003Csub\u003ENoninferiority\u2005\u003C\/sub\u003E\u0026lt;\u2005.001).\u003C\/p\u003E\n         \u003Cp id=\u0022p-20\u0022\u003EA number of other trials are ongoing, with results due over the next few years (\u003Ca id=\u0022xref-table-wrap-2-1\u0022 class=\u0022xref-table\u0022 href=\u0022#T2\u0022\u003ETable 2\u003C\/a\u003E). Dr Inzucchi emphasized that although these preliminary studies may report effects on CV markers and surrogates, these effects do not necessarily predict what will happen to patients in terms of actual clinical events in the CVOTs. In addition, while the drugs may present no CV safety signals during these trials, it may be overly optimistic to think that they will show any differences in effectiveness on CV end points over a period of just 2 to 4 years. And because the FDA has demanded the recruitment of high-risk patients into these CVOTs, there is some concern that the presence of advanced CV disease and an underlying predilection for further overt macrovascular complications will outweigh any possible CV benefits of a glucose-lowering drug.\u003C\/p\u003E\n         \u003Cdiv id=\u0022T2\u0022 class=\u0022table pos-float\u0022\u003E\u003Cdiv class=\u0022table-inline\u0022\u003E\u003Cdiv class=\u0022callout\u0022\u003E\u003Cspan\u003EView this table:\u003C\/span\u003E\u003Cul class=\u0022callout-links\u0022\u003E\u003Cli class=\u00220 first\u0022\u003E\u003Ca href=\u0022\/\u0022 class=\u0022table-expand-inline\u0022 data-table-url=\u0022\/highwire\/markup\/16534\/expansion?postprocessors=highwire_figures%2Chighwire_math%2Chighwire_inline_linked_media%2Chighwire_embed\u0026amp;table-expand-inline=1\u0022 html=\u00221\u0022 fragment=\u0022#\u0022 external=\u00221\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView inline\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00221\u0022\u003E\u003Ca href=\u0022\/highwire\/markup\/16534\/expansion?width=1000\u0026amp;height=500\u0026amp;iframe=true\u0026amp;postprocessors=highwire_figures%2Chighwire_math%2Chighwire_inline_linked_media\u0022 class=\u0022colorbox colorbox-load table-expand-popup\u0022 rel=\u0022gallery-fragment-tables\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView popup\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00222 last\u0022\u003E\u003Ca href=\u0022\/highwire\/powerpoint\/16534\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\u003Cdiv class=\u0022table-caption\u0022\u003E\u003Cspan class=\u0022table-label\u0022\u003ETable 2.\u003C\/span\u003E \n               \u003Cp id=\u0022p-21\u0022 class=\u0022first-child\u0022\u003EOngoing Cardiovascular Trials for Diabetes Drugs (Noninsulin)\u003C\/p\u003E\n            \u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\n         \u003Cp id=\u0022p-24\u0022\u003EDr Inzucchi then reviewed the updated 2015 American Diabetes Association\/European Association for the Study of Diabetes treatment algorithm for managing hypertension in T2DM (\u003Ca id=\u0022xref-fig-1-1\u0022 class=\u0022xref-fig\u0022 href=\u0022#F1\u0022\u003EFigure 1\u003C\/a\u003E). He noted that if any of the compounds included in 1 of the ongoing CVOTs were to show a CV benefit, the current treatment algorithm would likely be updated to reflect that benefit.\u003C\/p\u003E\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\/15\/4\/4\/F1.large.jpg?width=800\u0026amp;height=600\u0026amp;carousel=1\u0022 title=\u0022General Recommendations for Antihyperglycemic Therapy, T2DMGLP-1 RA, glucagon-like peptide 1 receptor agonist; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol; SGLT2i, sodium-glucose cotransporter-2 inhibitor; SU, sulfonylurea; T2DM, type 2 diabetes mellitus; TZD, thiazolidinedione.\u0026#x2020;Consider initial therapy at this stage when HbA1c is 9% (75 mmol\/mol).\u0026#x2021;Consider initial therapy at this stage when blood glucose is 300\u0026#x2013;350 mg\/dL (16.7\u0026#x2013;19.4 mmol\/L) and\/or HbA1c 10\u0026#x2013;12% (86\u0026#x2013;108 mmol\/mol), especially if patient is symptomatic or if catabolic features (weight loss, ketosis) are present, in which case basal insulin 1 mealtime insulin is the preferred initial regimen.\u0026#xA7;Usually a basal insulin (eg, NPH, glargine, detemir, degludec).Reproduced from Inzucchi SE et al. Management of Hyperglycemia in Type 2 Diabetes 2015: A Patient Centered Approach, Diabetes, 38, 2015, Copyright and all rights reserved. Material from this publication has been used with the permission of American Diabetes Association.\u0022 class=\u0022fragment-images colorbox-load\u0022 rel=\u0022gallery-fragment-images-866872524\u0022 data-figure-caption=\u0022\u0026amp;lt;div xmlns=\u0026amp;quot;http:\/\/www.w3.org\/1999\/xhtml\u0026amp;quot;\u0026amp;gt;General Recommendations for Antihyperglycemic Therapy, T2DMGLP-1 RA, glucagon-like peptide 1 receptor agonist; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol; SGLT2i, sodium-glucose cotransporter-2 inhibitor; SU, sulfonylurea; T2DM, type 2 diabetes mellitus; TZD, thiazolidinedione.\u0026#x2020;Consider initial therapy at this stage when HbA\u0026amp;lt;sub\u0026amp;gt;1c\u0026amp;lt;\/sub\u0026amp;gt; is 9% (75 mmol\/mol).\u0026#x2021;Consider initial therapy at this stage when blood glucose is 300\u0026#x2013;350 mg\/dL (16.7\u0026#x2013;19.4 mmol\/L) and\/or HbA\u0026amp;lt;sub\u0026amp;gt;1c\u0026amp;lt;\/sub\u0026amp;gt; 10\u0026#x2013;12% (86\u0026#x2013;108 mmol\/mol), especially if patient is symptomatic or if catabolic features (weight loss, ketosis) are present, in which case basal insulin 1 mealtime insulin is the preferred initial regimen.\u0026#xA7;Usually a basal insulin (eg, NPH, glargine, detemir, degludec).Reproduced from Inzucchi SE et al. Management of Hyperglycemia in Type 2 Diabetes 2015: A Patient Centered Approach, \u0026amp;lt;em\u0026amp;gt;Diabetes\u0026amp;lt;\/em\u0026amp;gt;, 38, 2015, Copyright and all rights reserved. Material from this publication has been used with the permission of American Diabetes Association.\u0026amp;lt;\/div\u0026amp;gt;\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\/15\/4\/4\/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\/15\/4\/4\/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\/15\/4\/4\/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\/16532\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\u003Cspan class=\u0022fig-label\u0022\u003EFigure 1.\u003C\/span\u003E \n               \u003Cp id=\u0022p-25\u0022 class=\u0022first-child\u0022\u003EGeneral Recommendations for Antihyperglycemic Therapy, T2DM\u003C\/p\u003E\n               \u003Cp id=\u0022p-26\u0022\u003EGLP-1 RA, glucagon-like peptide 1 receptor agonist; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol; SGLT2i, sodium-glucose cotransporter-2 inhibitor; SU, sulfonylurea; T2DM, type 2 diabetes mellitus; TZD, thiazolidinedione.\u003C\/p\u003E\n               \u003Cp id=\u0022p-27\u0022\u003E\u2020Consider initial therapy at this stage when HbA\u003Csub\u003E1c\u003C\/sub\u003E is 9% (75 mmol\/mol).\u003C\/p\u003E\n               \u003Cp id=\u0022p-28\u0022\u003E\u2021Consider initial therapy at this stage when blood glucose is 300\u2013350 mg\/dL (16.7\u201319.4 mmol\/L) and\/or HbA\u003Csub\u003E1c\u003C\/sub\u003E 10\u201312% (86\u2013108 mmol\/mol), especially if patient is symptomatic or if catabolic features (weight loss, ketosis) are present, in which case basal insulin 1 mealtime insulin is the preferred initial regimen.\u003C\/p\u003E\n               \u003Cp id=\u0022p-29\u0022\u003E\u00a7Usually a basal insulin (eg, NPH, glargine, detemir, degludec).\u003C\/p\u003E\n               \u003Cp id=\u0022p-30\u0022\u003EReproduced from Inzucchi SE et al. Management of Hyperglycemia in Type 2 Diabetes 2015: A Patient Centered Approach, \u003Cem\u003EDiabetes\u003C\/em\u003E, 38, 2015, Copyright and all rights reserved. Material from this publication has been used with the permission of American Diabetes Association.\u003C\/p\u003E\n            \u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\n         \u003Cp id=\u0022p-31\u0022\u003EIn closing, Dr Inzucchi emphasized that although diabetes confers additional CV disease risk, glycemic control itself appears to only modestly reduce nonfatal MI. Any benefit from glycemic control will likely have to accrue over many years and may be negated by progressive atherosclerosis. The ideal glucose-lowering agent will reduce CV events as well as maintain glycemic control. For now, however, glycemic control should be used mainly to prevent microvascular complications, while control of lipids and BP is the best means for preventing macrovascular complications.\u003C\/p\u003E\n      \u003C\/div\u003E\u003Cul class=\u0022copyright-statement\u0022\u003E\u003Cli class=\u0022fn\u0022 id=\u0022copyright-statement-1\u0022\u003E\u00a9 2015 SAGE Publications\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\/15\/4\/4.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?nzlmo1\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?nzlmo1\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_tables.js?nzlmo1\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}