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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\u003EFrom a biological perspective, there are many advantages to inhaled insulin: the lung has a large surface area and a thin blood barrier, inhaled administration avoids first pass liver clearance, and transport of the medication is rapid and efficient. From a quality of life perspective, perhaps the biggest advantage of inhaled insulin is its mode of delivery.\u003C\/p\u003E\n         \u003C\/div\u003E\u003Cul class=\u0022kwd-group\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003Eendocrinology\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Ediabetes \u0026amp; metabolic syndrome\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Einsulin\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\/6\/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-900960266\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\/6\/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\/6\/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\/6\/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\/10840\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\u003EFrom a biological perspective, I there are many advantages to inhaled insulin: the lung has a large surface area and a thin blood barrier, inhaled administration avoids first pass liver clearance, and transport of the medication is rapid and efficient. From a quality of life perspective, perhaps the biggest advantage of inhaled insulin is its mode of delivery. Exubera\u00ae, an inhaled human insulin co-developed by Pfizer and Aventis, has been FDA approved and became available to patients in the US in July 2006. Exubera\u00ae was granted marketing authorization by the EU Commission in January 2006. In addition, six other pharmaceutical companies have inhaled insulin products in development. As these products represent a completely new insulin delivery mechanism, there is obviously a great deal of interest in their effectiveness, safety, and introduction to the marketplace.\u003C\/p\u003E\n         \u003Cp id=\u0022p-3\u0022\u003EThe pharmacokinetics of inhaled insulin differ from injected insulin. Serum insulin levels peak more quickly with inhaled insulin compared to regular human insulin administered subcutaneously (49 minutes vs. 105 minutes, respectively). In terms of pharmacodynamics, the duration of glucose-lowering activity of inhaled insulin is comparable to regular human insulin. The within-subject variability of inhaled insulin is comparable to that of regular human insulin. These findings appear to be consistent in patients with either type 1 or type 2 diabetes.\u003C\/p\u003E\n         \u003Cp id=\u0022p-4\u0022\u003EJoseph Brain, ScD of Harvard University gave an overview of inhaled insulin and the associated pulmonary safety issues. There are several reasons that clinicians need to choose carefully which patients are candidates for inhaled insulin. Obesity adversely affects lung volume and respiratory function and increases the risk of asthma and abnormal pulmonary function. Pulmonary microcirculation is also adversely affected by poor glycemic control.\u003C\/p\u003E\n         \u003Cp id=\u0022p-5\u0022\u003EIn rats and monkeys treated with inhaled insulin, no pathologic respiratory or significant immunologic changes were observed. However, the doses that could be used were limited because extremely high doses led to hypoglycemia.\u003C\/p\u003E\n         \u003Cp id=\u0022p-6\u0022\u003EStudies comparing the effects of inhaled insulin and oral agents on pulmonary function in humans have not shown evidence of airway sensitization, and no acute adverse effects occurred after insulin was inhaled. There was a small decrease in forced expiratory volume at one second (FEV\u003Csub\u003E1\u003C\/sub\u003E) and carbon monoxide diffusing capacity (DL\u003Csub\u003Eco\u003C\/sub\u003E). These decreases occurred in the first few weeks of treatment, did not progress, and returned to baseline values after inhaled insulin was discontinued. Because of these concerns, patients need to have a spirometric pulmonary assessment and cannot take inhaled insulin if their lung function is \u0026lt;70% of expected (per the Exubera\u00ae label). Slight increases in dyspnea and mild cough are common side effects reported in using Exubera\u00ae. Dr. Brain advocated the conduct of long term post-marketing studies 5\u201310 years in length, as the data collected at this point go out only to 2 years.\u003C\/p\u003E\n         \u003Cp id=\u0022p-7\u0022\u003EDuring its development, inhaled insulin has been used in several different studies in both type 1 and type 2 diabetes. In two 24-week studies conducted in patients with type 1 diabetes, the decrease in HbA1c and number of episodes of hypoglycemia were comparable between inhaled insulin and regular insulin. A summary of the clinical data is presented in the table below.\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\/10841\/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\/10841\/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\/10841\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\u003C\/div\u003E\n         \u003Cp id=\u0022p-13\u0022\u003EIn patients with type 2 diabetes, one open-label study explored the use of inhaled insulin both as monotherapy and as an adjunct to oral antidiabetic (OA) therapy in patients who were not well-controlled using OAs alone. Patients were randomized to one of three arms and were treated for 12 weeks. The incidence of hypoglycemia was slightly higher in the two inhaled insulin groups when compared to the OAs alone. Other results are presented in the following table.\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\/10843\/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\/10843\/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\/10843\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\u003C\/div\u003E\n         \u003Cp id=\u0022p-17\u0022\u003EJulio Rosenstock, MD of the Southwestern Medical Center gave advice on selecting the appropriate patients for inhaled insulin therapy. In his experience, patients seem to find it easy to use and like using it, but it is contraindicated in patients who smoke, have underlying lung disease, are pregnant, and in pediatric patients. In type 1 diabetes, it should be used in combination with long-acting insulin. In type 2 diabetes, it could be used as monotherapy or in combination with long-acting insulin. He believes that inhaled insulin represents another option for stable patients with type 1 diabetes, and has great potential in type 2 diabetic patients.\u003C\/p\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\/6.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\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_tables.js?nzlz4d\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}