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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\u003EThe basal insulin analog LY2605541 (LY) is a long-acting, PEGylated insulin lispro that is designed with a large hydrodynamic size, which delays insulin absorption and reduces clearance, resulting in prolonged duration of action. LY demonstrates a preferential hepatic effect compared with human insulin in a somatostatin-infused\/glucagon-replaced conscious dog model [Moore MC et al. ADA 2012 Abstract 1609P]. This article discusses data that showed that in a continuously glucose-monitored cohort of patients with type 2 diabetes mellitus, those receiving LY had lower intra-day glucose variability and fewer and shorter episodes of hypoglycemia compared with patients receiving glargine.\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\u003EInsulin\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EHyperglycemia\/Hypoglycemia\u003C\/li\u003E\u003C\/ul\u003E\u003Cp id=\u0022p-2\u0022\u003EThe basal insulin analog LY2605541 (LY) is a long-acting, PEGylated insulin lispro that is designed with a large hydrodynamic size, which delays insulin absorption and reduces clearance, resulting in prolonged duration of action. LY demonstrates a preferential hepatic effect compared with human insulin in a somatostatin-infused\/glucagon-replaced conscious dog model [Moore MC et al. ADA 2012 Abstract 1609P]. Richard Bergenstal, MD, International Diabetes Center, Park Nicollet, Minneapolis, Minnesota, USA, presented data that showed that in a continuously glucose-monitored cohort of patients with type 2 diabetes mellitus (T2DM), those receiving LY had lower intra-day glucose variability and fewer and shorter episodes of hypoglycemia compared with patients receiving glargine.\u003C\/p\u003E\u003Cp id=\u0022p-3\u0022\u003EHypoglycemia and glucose variability were assessed with continuous glucose monitoring (CGM) of interstitial glucose (IG) in a subset of patients from a Phase 2, randomized, open-label, parallel study of T2DM patients who were administered LY (n=51) or insulin glargine (GL; n=25). CGM was conducted on 3 consecutive days (72 to 84 hours) during the week before Week 0, 6, and 12 study visits. A hypoglycemic episode was defined as IG \u226470 mg\/dL and continued until IG was \u0026gt;70 mg\/dL for 15 minutes (or 3 time points).\u003C\/p\u003E\u003Cp id=\u0022p-4\u0022\u003EAt 12 weeks, LY-treated patients spent less time with IG \u0026lt;70 mg\/dL than GL-treated patients during the 24-hour period (25\u00b16 versus 83\u00b116 min; p=0.01) and during the nocturnal period (11\u00b15 versus 38\u00b113 min; p=0.024). Significantly fewer LY- than GL-treated patients experienced hypoglycemia (50.0% versus 78.3%; p=0.036), including nocturnal hypoglycemia (20.5% versus 47.8%; p=0.027) [IMAGINE 1\u20135; \u003Ca class=\u0022external-ref external-ref-type-clintrialgov\u0022 href=\u0022\/lookup\/external-ref?link_type=CLINTRIALGOV\u0026amp;access_num=NCT01481779\u0026amp;atom=%2Fspmdc%2F12%2F10%2F14.atom\u0022\u003ENCT01481779\u003C\/a\u003E;  \u003Ca class=\u0022external-ref external-ref-type-clintrialgov\u0022 href=\u0022\/lookup\/external-ref?link_type=CLINTRIALGOV\u0026amp;access_num=NCT01435616\u0026amp;atom=%2Fspmdc%2F12%2F10%2F14.atom\u0022\u003ENCT01435616\u003C\/a\u003E;  \u003Ca class=\u0022external-ref external-ref-type-clintrialgov\u0022 href=\u0022\/lookup\/external-ref?link_type=CLINTRIALGOV\u0026amp;access_num=NCT01454284\u0026amp;atom=%2Fspmdc%2F12%2F10%2F14.atom\u0022\u003ENCT01454284\u003C\/a\u003E;  \u003Ca class=\u0022external-ref external-ref-type-clintrialgov\u0022 href=\u0022\/lookup\/external-ref?link_type=CLINTRIALGOV\u0026amp;access_num=NCT01468987\u0026amp;atom=%2Fspmdc%2F12%2F10%2F14.atom\u0022\u003ENCT01468987\u003C\/a\u003E;  \u003Ca class=\u0022external-ref external-ref-type-clintrialgov\u0022 href=\u0022\/lookup\/external-ref?link_type=CLINTRIALGOV\u0026amp;access_num=NCT01582451\u0026amp;atom=%2Fspmdc%2F12%2F10%2F14.atom\u0022\u003ENCT01582451\u003C\/a\u003E]. Further CGM evaluation is ongoing in Phase 3 studies of LY2605541 in patients with type 1 diabetes mellitus (T1DM) and T2DM.\u003C\/p\u003E\u003Cp id=\u0022p-5\u0022\u003EInsulin degludec (IDeg) is a new-generation, ultralong-acting basal insulin, offered in 100-U\/mL and 200-U\/mL doses. Previous T1DM studies have identified the IDeg 100-U\/mL dose as having a flat and stable action profile, with the ability to control glucose beyond 42 hours. Steady-state is reached within 2 to 3 days, and terminal half-life is twice (25.4 hrs) as long as that of insulin glargine (12.5 hrs) [Heise T et al. \u003Cem\u003EDiabetologia\u003C\/em\u003E 2011; Heise T et al. ADA 2012 Abstract 1013P].\u003C\/p\u003E\u003Cp id=\u0022p-6\u0022\u003ETim Heise, MD, Profil Institut f\u00fcr Stoffwechselforschung, Neuss, Germany, presented pharmacodynamic and pharmacokinetic data for the 200-U\/mL (0.6 U\/kg once daily over 6 days) dose of IDeg in T2DM patients (n=16; mean body mass index (BMI), 30 kg\/m\u003Csup\u003E2\u003C\/sup\u003E; HbA1C, 7.3%; age, 59.4 years). On Day 6, while at steady state, a 26-hour euglycemic glucose clamp was conducted (Biostator; clamp blood glucose level: 90 mg\/dL). The mean glucose infusion rate for the IDeg 200-U dose was flat and stable over the dosing interval and similar to the 100-U dose (\u003Ca id=\u0022xref-fig-1-1\u0022 class=\u0022xref-fig\u0022 href=\u0022#F1\u0022\u003EFigure 1\u003C\/a\u003E). The glucose-lowering effect of IDeg was evenly distributed over the 24-hour dosing interval. The effect of IDeg extended beyond 26 hours in all subjects. The terminal half-life at steady state was 25.1 hours. IDeg 200-U\/mL was well tolerated and safe, with no injection site reactions. IDeg 200-U\/mL has a flat, stable glucose-lowering effect and ultralong duration of action, with pharmacodynamic and pharmacokinetic characteristics that are similar to the 100-U\/mL dose.\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\/10\/14\/F1.large.jpg?width=800\u0026amp;height=600\u0026amp;carousel=1\u0022 title=\u0022IDeg: Glucose-Lowering Effect at Steady State.\u0022 class=\u0022fragment-images colorbox-load\u0022 rel=\u0022gallery-fragment-images-1370892900\u0022 data-figure-caption=\u0022IDeg: Glucose-Lowering Effect at Steady State.\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\/12\/10\/14\/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\/10\/14\/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\/12\/10\/14\/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\/12735\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-7\u0022 class=\u0022first-child\u0022\u003EIDeg: Glucose-Lowering Effect at Steady State.\u003C\/p\u003E\n         \u003Cq class=\u0022attrib\u0022 id=\u0022attrib-1\u0022\u003EReproduced with permission from T Heise, MD.\u003C\/q\u003E\u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cp id=\u0022p-8\u0022\u003EHepatopreferential insulin analogs functionally restore the physiological insulin gradient that is lost when insulin is delivered subcutaneously. Normalizing the distribution of insulin\u0027s effects at the liver versus nonhepatic tissues may reduce glycemic fluctuations, correct dyslipidemia, decrease vascular disease, reduce weight, limit hypoglycemic risk, and increase hepatic glucose uptake and glycogen storage. Dale S. Edgerton, PhD, Vanderbilt University Medical Center, Nashville, Tennessee, USA, presented results from an animal study that showed the peripheral delivery of a novel hepatopreferential insulin analog (insulin 327) leads to delayed suppression of lipolysis, greater effect on liver glucose metabolism, and reduced effect on nonhepatic glucose uptake compared with regular insulin delivered by the same route. Dogs with arterial, portal, and hepatic vein catheters were studied after an 18-hour fast. \u003Csup\u003E3\u003C\/sup\u003EH-glucose was infused from \u2212140 min. After a basal period (\u221240 to 0 min), somatostatin and basal portal glucagon were infused (0 to 300 min). At the same time, insulin 327 or human insulin (HI) was infused into a peripheral vein (7.2 or 1.8 pmol\/kg\/min, respectively; n=5\/group), and euglycemia was maintained by glucose infusion. Suppression of lipolysis was delayed with insulin 327 compared with HI: during the first hour, plasma nonesterified fatty acid levels (\u00b5mol\/L) decreased by 91\u00b137 versus 419\u00b142, respectively, and blood glycerol levels (\u00b5mol\/L) fell by 0\u00b17 versus 39\u00b15, respectively. Arterial insulin 327 and HI levels increased to 10,870\u00b12543 and 95\u00b18 pmol\/L, respectively (\u003Ca id=\u0022xref-fig-2-1\u0022 class=\u0022xref-fig\u0022 href=\u0022#F2\u0022\u003EFigure 2\u003C\/a\u003E).\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\/12\/10\/14\/F2.large.jpg?width=800\u0026amp;height=600\u0026amp;carousel=1\u0022 title=\u0022Glucose Appearance and Utilization.\u0022 class=\u0022fragment-images colorbox-load\u0022 rel=\u0022gallery-fragment-images-1370892900\u0022 data-figure-caption=\u0022Glucose Appearance and Utilization.\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\/12\/10\/14\/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\/12\/10\/14\/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\/12\/10\/14\/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\/12736\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-9\u0022 class=\u0022first-child\u0022\u003EGlucose Appearance and Utilization.\u003C\/p\u003E\n         \u003Cq class=\u0022attrib\u0022 id=\u0022attrib-2\u0022\u003EReproduced with permission from DS Edgerton, PhD.\u003C\/q\u003E\u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cp id=\u0022p-10\u0022\u003ERelative to the basal period, insulin 327 suppressed net hepatic glucose balance and glucose production (mg\/kg\/min; last 3 h) by 1.9\u00b10.1 and 1.7\u00b10.1, respectively, while HI reduced them by only 0.5\u00b10.6 and 1.1\u00b10.3. On the other hand, insulin 327 increased nonhepatic glucose uptake and glucose utilization (mg\/kg\/min; last 3 h) by only 1.0\u00b10.4 and 1.5\u00b10.3, respectively, while HI increased them by 2.4\u00b11.2 and 2.5\u00b11.1. Liver-preferential insulin analogs may provide a therapeutic benefit by functionally restoring the physiological insulin gradient at the liver compared with peripheral tissues.\u003C\/p\u003E\u003Cp id=\u0022p-11\u0022\u003ERecombinant human hyaluronidase (rHuPH20) is a genetically engineered soluble version of the naturally occurring human hyaluronidase enzyme that is used to accelerate absorption and action of insulin and, thus, improve prandial glucose control. It has a history of more than 60 years of safe clinical use. The aim of this study was to compare rapid-acting analog insulin that is formulated with rHuPH20 versus insulin lispro alone on glycemic control parameters, safety, and tolerability in an intensive basal-bolus insulin therapy in patients with type 1 diabetes [Phase II Study Evaluating Pharmacokinetics and Postprandial Glycemic Response of Subcutaneously Injected Humalog and Humlin R With\/Without Co Injected Recombinant Human Hyaluronidase Following Liquid Meal in Type1 Diabetes Mellitus Patients; \u003Ca class=\u0022external-ref external-ref-type-clintrialgov\u0022 href=\u0022\/lookup\/external-ref?link_type=CLINTRIALGOV\u0026amp;access_num=NCT00774800\u0026amp;atom=%2Fspmdc%2F12%2F10%2F14.atom\u0022\u003ENCT00774800\u003C\/a\u003E]. The results were presented by Irl B. Hirsch, MD, University of Washington School of Medicine, Seattle, Washington, USA.\u003C\/p\u003E\u003Cp id=\u0022p-12\u0022\u003EAfter a 4- to 6-week run-in using prandial glulisine plus glargine (BID), 117 subjects (mean: age 42.6\u00b114 years; BMI, 27.3\u00b14.4 kg\/m\u003Csup\u003E2\u003C\/sup\u003E; HbA1C, 6.7% to 8.3%) were randomly assigned (double-blind crossover) to lispro plus rHuPH20 or aspart plus rHuPH20 versus lispro alone for 2 12-week intensive management periods; prandial doses were given immediately before meals. The primary endpoint of HbA1C noninferiority (0.4% margin) was achieved with no treatment difference (95% CI, \u22120.05 to 0.15). Overall hypoglycemic rates (\u226470 mg\/dL or symptoms) were reduced 5% (p=0.035), and events \u0026lt;56 mg\/dL were reduced 7% (p=0.045). Total daily insulin dose (54\u00b127 for analog-PH20 versus 56\u00b127 U for lispro; p=0.057) and weight gain difference (\u22120.57 lb; p=0.27) showed favorable trends. No meaningful differences in adverse events, immunogenicity, or injection-site pain were noted. Flatter daytime glucose profiles and an 82% reduction in postprandial glucose excursions suggest that analog-PH20 offers improved postprandial glucose control.\u003C\/p\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\/10\/14.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?nzneqp\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?nzneqp\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}