bluuebunny/crossref_metadata_2025_split huggingface dataset:
Treatment Effects of Once-Weekly Dulaglutide vs. Insulin Glargine in Patients with Different Baseline Glycemic Patterns (Based on High/Low Fasting or High/Low Postprandial Glucose)—A Post-Hoc Analysis of the AWARD-2 Clinical Trial
Authors: GIORGINO FRANCESCO , YU MARIA , HAUPT AXEL , MILICEVIC ZVONKO , GARCIA-PEREZ LUIS-EMILIO 
Published: June 2018

Insulin glargine (Glar) exerts its action primarily through a decrease in fasting plasma glucose (FPG), whereas dulaglutide (DU), a once-weekly GLP-1RA, targets both fasting and postprandial glucose (PPG). This post-hoc analysis of the AWARD-2 study assessed the efficacy of DU vs. Glar in patients with type 2 diabetes with different glycemic patterns at baseline determined by self-monitoring of blood glucose (fasting glucose [FG] vs. PPG). Patients were categorized into 4 groups based on combinations of low and high FG and PPG, with median baseline values of FG (151 mg/dL) and PPG (182 mg/dL) being used as threshold for low and high, respectively. Analyses were conducted using analysis of covariance. DU showed a statistically significantly greater reduction in A1c compared with Glar for all of the subgroups, except for low FG/high PPG, where the numerical difference was in favor of DU but did not reach statistical significance (Table). Total hypoglycemia was numerically lower for DU vs. Glar in all subgroups. DU showed efficacy on A1c reductions across different baseline glycemic patterns vs. Glar (with the exception of low FG/high PPG), indicating a clinical benefit of targeting both FG and PPG, irrespective of the baseline glycemic phenotype.

Disclosure
F. Giorgino: Consultant; Self; Abbott, AstraZeneca, Boehringer Ingelheim GmbH. Research Support; Self; Eli Lilly and Company, Johnson & Johnson Services, Inc.. Consultant; Self; MedImmune, Merck Sharp & Dohme Corp., Roche Diabetes Care Health and Digital Solutions, Sanofi. Research Support; Self; Takeda Development Centre Europe Ltd. M. Yu: Employee; Self; Eli Lilly and Company. A. Haupt: Employee; Self; Eli Lilly and Company. Stock/Shareholder; Self; Eli Lilly and Company. Z. Milicevic: Employee; Self; Eli Lilly and Company. L. Garcia-Perez: Employee; Self; Eli Lilly and Company. Stock/Shareholder; Self; Eli Lilly and Company.
The Effect of Temperature on the Stability of In-Use Insulin Pens
Authors: KONGMALAI TANAWAN , PREECHASUK LUKANA , JUNNU SARAWUT , MANOCHEEWA SIRIPHAN , SRISAWAT CHATCHAWAN , SRIWIJITKAMOL APIRADEE 
Published: June 2018

Background: Improper storage of in use insulin could decrease its potency. Temperature has been shown to have an effect on the stability of insulin. Therefore, the manufacturers recommend to keep an in use insulin at the room temperature (RT), not exceeding 25-30 ๐C. However, The RT in tropical countries are higher than that. Thus far, there are few studies evaluate the effect of temperature on insulin stability, especially insulin pens which are widely used nowadays.
Aim: To investigate the effect of temperature on the stability of basal insulin after opening for 28 days.
Methods: There are four different commercial basal insulin pens, including long and intermediate acting insulin were evaluated (N=5 each). They were opened and stored at 3 different conditions, including: refrigerated (2-8 ๐C), RT and incubator (37 ๐C) for 28 days. An unopened insulin pens from the same batches were stored under standard condition as control (CON). During the study period, the insulin pens were well-mixed and discarded 2 units every day to mimic the daily usage of diabetes patient. The temperature logger was used to record the hourly temperature in RT. After 28 days, the amount of insulin was evaluated using the Ultra-high performance liquid chromatography assay.
Results: Average RT throughout the study period was 29.7 ± 2.8 ๐C. The percentage amount of insulin (mean ± SD) stored at 4oC, RT or 37oC, compared with CON was as follows: 99.0 ± 0.8%, 99.7 ± 2.5%, 101.1 ± 1.2% for long-acting insulin; 97.4 ± 0.7%, 97.2 ± 1.6%, 99.0 ± 1.2% for NPH-1; 101.4 ± 1.1%, 101.5 ± 2.5%, 100.7 ± 2.3% for NPH-2; and 98.7 ± 1.5%, 97.8 ± 1.1%, 98.5 ± 1.7% for NPH-3. There was no statistically significant in the difference. However, there was a trend toward different in AUC between long acting and NPH insulin.
Conclusion: Temperature, as high as 37 ๐C, cyclic temperature and the variability of temperature range from 4 ๐C to room temperature had no effect on the stability of in use insulin pen. We observed the trend toward different in stability between clear insulin analog and turbid NPH insulin.

Disclosure
T. Kongmalai: None. L. Preechasuk: None. S. Junnu: None. S. Manocheewa: None. C. Srisawat: None. A. Sriwijitkamol: None.
Ultra-rapid Lispro (URLi) Reduces Postprandial Glucose Excursions vs. Humalog® in Patients with T1D at Multiple Meal-to-Dose Timing Intervals
Authors: PLUM-MOERSCHEL LEONA , LEOHR JENNIFER , LIU RONG , REDDY SHOBHA , DELLVA MARY A. , LIM SHUFEN , MEI TENG LOH , KNADLER MARY P. , HARDY THOMAS , KAZDA CHRISTOF M. 
Published: June 2018

URLi (LY900014), a novel ultra-rapid mealtime insulin in Phase 3 development, is shown to reduce postprandial glucose after subcutaneous injection. This 2-part, randomized, double-blind, Phase 1b study evaluated the differences in PK and PD between URLi and insulin lispro (Humalog®; HL) in 30 patients with T1D. Part A used a 6´period crossover design to evaluate safety and compare PK and postprandial glucose response to solid mixed meal tolerance tests (MMTT) with URLi or HL at different injection to mealtime intervals (-15, 0, and +15 min). Part B evaluated the safety, PK, and PD during 2 weeks of multiple daily dosing (immediately before a meal) in a parallel design. In Part A, URLi reduced glucose excursions (assessed as change in area under the concentration curve vs. time [∆AUC]) during the first 2 hours (∆AUC0-2h) and entire 5 hours (∆AUC0´5h) of the MMMT regardless of dose timing (Fig). URLi reduced ∆AUC0-2h by 103% (p=0.008), 39% (p=0.031), and 16% (p=0.096), and ∆AUC0-5h by 40% (p=NS), 44% (p=0.097), and 42% (p=0.026) vs. HL at -15, 0, and +15 min (significance level =0.1. The PK and PD profiles for URLi and HL were sustained after 2 weeks of outpatient dosing (Part B). Similar number of hypoglycemic events occurred between treatments during MMTTs. During 2 weeks of outpatient dosing, the number of events was lower for URLi vs. HL. Local tolerability was similar between treatments.

Disclosure
L. Plum-Moerschel: None. J. Leohr: Employee; Self; Eli Lilly and Company. Stock/Shareholder; Self; Eli Lilly and Company. Employee; Spouse/Partner; Accenture. Stock/Shareholder; Spouse/Partner; Accenture. R. Liu: Employee; Self; Eli Lilly and Company. Employee; Spouse/Partner; Eli Lilly and Company. S. Reddy: None. M.A. Dellva: Employee; Self; Eli Lilly and Company. S. Lim: None. M. Loh: Employee; Self; Eli Lilly and Company. M.P. Knadler: Other Relationship; Self; Eli Lilly and Company. T. Hardy: Employee; Self; Eli Lilly and Company. Stock/Shareholder; Self; Eli Lilly and Company. C.M. Kazda: Employee; Self; Eli Lilly and Company.
One-Year Safety and Effectiveness of Insulin Degludec in Patients with Diabetes Mellitus in Routine Clinical Practice in India—TRUST (Tresiba Real-World Use Study)
Authors: KESAVADEV JOTHYDEV , MURTHY L. SREENIVASA , SABOO BANSHI D. , YALAMANCHI SADASIVA RAO , RAMANATHAN BALAMURUGAN , GUPTA SUNIL , CHATTERJEE SANJAY , REVANNA MANJUNATHA , KASETTY HARSHA 
Published: June 2018

Insulin degludec (degludec) is a basal insulin with an ultra-long duration of action and low day-to-day variability in the glucose-lowering effect. The aim of this non-interventional, multicentric, prospective, post-authorization safety study (PASS) was to evaluate the long-term (1 year) safety and effectiveness of insulin degludec in patients with diabetes mellitus (DM) requiring insulin therapy on routine clinical practice conditions, as required by the Indian regulatory authority. Eligible patients who were started with degludec treatment as per the physician’s discretion were followed up and data was collected at baseline (BL), 3, 6 and 12 months in the time periods after degludec initiation. Values are expressed as mean (SD). A total of 1057 adult patients with DM (5 with T1D and 1052 with T2D) were included. In total, 59.6% were male, mean age 55.9 (11.5) years, duration of diabetes 11.4 (7.6) years, body weight 71.6 (13.7) kg and HbA1c 9.6 (1.9)%]. Majority of the subjects (81.83%) were insulin-naïve at BL. At 12 months follow-up, 44 adverse events (AEs) were reported in 2.6% of the subjects and 2 AEs were serious. HbA1c decreased significantly compared to BL by 1.8% (1.68) (p&lt;0.0001). Daily degludec dose increased from a starting dose of 14.8 (8.0) U to 18.01 (9.45) U and body weight increased from 71.68 (13.43) kg (BL) to 72.24 (12.88) kg. Hypoglycemia was reported in 5% of the subjects (8.5 events/ 100PYE) during the 12 months treatment period. The two most common reasons for prescribing degludec were to improve HbA1c (83.8%) and for control of fasting glucose (63.7%).
In conclusion, this PASS confirms the long-term safety of treatment with degludec with improvement in glycemic control and low risk of hypoglycemia in patients with T2D on routine clinical care.

Disclosure
J. Kesavadev: Advisory Panel; Self; Novo Nordisk India Private Limited. Speaker's Bureau; Self; Novo Nordisk India Private Limited. Advisory Panel; Self; Medtronic. Speaker's Bureau; Self; Medtronic. Advisory Panel; Self; Sanofi. Speaker's Bureau; Self; Sanofi. Research Support; Self; MSD. Speaker's Bureau; Self; MSD. Advisory Panel; Self; AstraZeneca. Speaker's Bureau; Self; AstraZeneca. L. Murthy: None. B.D. Saboo: None. S. Yalamanchi: None. B. Ramanathan: Speaker's Bureau; Self; Novo Nordisk India Private Limited, Eli Lilly and Company, Boehringer Ingelheim, Sanofi-Aventis, Zydus Pharmaceuticals, USV Private Limited, DR.REDDY'S LABORATORIES, AstraZeneca, Biocon, Johnson and Johnson, MSD, Novartis, Glenmark, Abbott. S. Gupta: Speaker's Bureau; Self; Novo Nordisk India Private Limited, MSD, AstraZeneca, Novartis, USV Private Limited, Abbott. S. Chatterjee: None. M. Revanna: Employee; Self; Novo Nordisk India Private Limited. H. Kasetty: Employee; Self; Novo Nordisk India Private Limited.
Low Doses of Dasiglucagon Consistently Increase Plasma Glucose (PG) Levels in Hypoglycemia and Euglycemia in People with Type 1 Diabetes Mellitus (T1DM)
Authors: HOVELMANN ULRIKE , BRAENDHOLT OLSEN MINNA , MOURITZEN ULRIK , LAMERS DANIELA , KRONSHAGE BIRGIT , HEISE TIM 
Published: June 2018

To develop a dual hormone artificial pancreas (DHAP) a liquid stable glucagon component is needed. Currently available glucagon products have limited stability after reconstitution and are therefore not suited for DHAP usage. Dasiglucagon is a novel liquid stable glucagon analog, which does not require mixing prior to use. In this randomized double-blind trial 17 patients with T1DM received four single subcutaneous doses (0.03, 0.08, 0.2 and 0.6 mg) of dasiglucagon (4 mg/ml) under hypoglycemic (plasma glucose (PG) 56-66 mg/dL) or euglycemic (PG 100 mg/dL) conditions. For comparison, identical doses of Lilly GlucagonTM (GLUCA) were investigated at euglycemia. In the euglycemic setting dasiglucagon showed rapid and dose-dependent PG-increases of mean 39, 56, 72 and 80 mg/dL at 30 minutes post-dosing (30, 49 and 71 mg/dl for GLUCA) (Figure). During hypoglycemia, dasiglucagon provided similar PG-increases of 24, 64, 87 and 94 mg/dL 30 minutes post dose and rapidly corrected PG levels to normoglycemia (PG ?70 mg/dL) with a median time of 14, 10, 6 and 6 minutes.
In conclusion, low doses of dasiglucagon rapidly and effectively increase PG from euglycemia and hypoglycemia in a titratable manner. Therefore, dasiglucagon should be a good candidate for use in dual-hormone closed-loop AP systems.Figure. Different Doses of Dasiglucagon and GLUCA, PG Levels (Mean ±SEM).

Disclosure
U. Hovelmann: None. M. Braendholt Olsen: Stock/Shareholder; Self; Novo Nordisk A/S. Employee; Self; Zealand Pharma A/S. U. Mouritzen: Employee; Self; Zealand Pharma A/S. Stock/Shareholder; Self; Novo Nordisk A/S. D. Lamers: None. B. Kronshage: None. T. Heise: Research Support; Self; ADOCIA, Boehringer Ingelheim GmbH, Dance Biopharm, Eli Lilly and Company, Janssen Research & Development, MedImmune, Merck Sharp & Dohme Corp., Mylan, Nordic Bioscience, Novo Nordisk A/S, Poxel SA, Roche Diagnostics Corporation, Saniona, Sanofi, Senseonics, Zealand Pharma A/S. Advisory Panel; Self; Novo Nordisk A/S, Mylan. Speaker's Bureau; Self; Dexcom, Inc., Eli Lilly and Company, Novo Nordisk A/S, Sanofi.
Self-Managed Titration with Insulin Glargine 300 U/mL (Gla-300) Can Achieve Similar Efficacy to Physician-Led Titration Regardless of Prior Insulin Status in People with T2DM—Results from TAKE CONTROL
Authors: DELGADO ELIAS , BONNEMAIRE MIREILLE , DAUCHY ARNAUD , DONICOVA VIERA , KVAPIL MILAN , TENTOLOURIS NIKOLAOS , POPESCU LUIZA , RUSSELL-JONES DAVID 
Published: June 2018

Many people with T2DM do not achieve HbA1c goals in clinical practice, owing in part to sub-optimal basal insulin titration. TAKE CONTROL, a 24-week, multicenter, randomized, open-label, parallel-group study, compared the efficacy and safety of a Gla-300 titration algorithm (fasting self-monitored plasma glucose &gt;130 mg/dL, +3 U; &lt;80 mg/dL, −3 U), when self-managed or led by physicians. Overall, improved glycemic control without increased hypoglycemia was seen with self-titration. Here, we report results stratified by prior insulin use. At baseline, mean HbA1c was higher in the insulin-naïve vs. prior-insulin group (Table). In both groups, self-titration and physician-led titration resulted in similar HbA1c reduction. For confirmed or severe hypoglycemia, there was no evidence of heterogeneity between titration approaches for both glycemic thresholds (≤70 mg/dL or &lt;54 mg/dL). Glycemic goal achievement with Gla-300 using self-titration was similar to that reported for physician-led titration, regardless of prior insulin use, but with reduced or similar risk of hypoglycemia. Empowering people with T2DM to self-titrate their basal insulin effectively upon Gla-300 initiation, or after switching to Gla-300, can improve glycemic target achievement without increasing hypoglycemia.

Disclosure
E. Delgado: Advisory Panel; Self; AstraZeneca. Speaker's Bureau; Self; AstraZeneca, Novo Nordisk A/S. Advisory Panel; Self; Sanofi-Aventis. Speaker's Bureau; Self; Sanofi-Aventis. Research Support; Self; Sanofi-Aventis. Speaker's Bureau; Self; Esteve, Boehringer Ingelheim Pharmaceuticals, Inc., Janssen Pharmaceuticals, Inc.. Advisory Panel; Self; Abbott. Speaker's Bureau; Self; Lilly. Research Support; Self; Menarini Group. M. Bonnemaire: Employee; Self; Sanofi. Stock/Shareholder; Self; Sanofi. A. Dauchy: Employee; Self; Sanofi. Stock/Shareholder; Self; Sanofi. V. Donicova: None. M. Kvapil: None. N. Tentolouris: Advisory Panel; Self; MSD K.K., AstraZeneca, Sanofi, Novo Nordisk A/S, Elpen Pharmaceutical Co. Inc., Eli Lilly and Company, Boehringer Ingelheim GmbH, Novartis AG. Research Support; Self; MSD K.K., Eli Lilly and Company, Novo Nordisk A/S, Sanofi, Pfizer Inc., AstraZeneca, Janssen-Cilag Pty Limited, GlaxoSmithKline plc., Novartis AG. L. Popescu: Employee; Self; Sanofi. Stock/Shareholder; Self; Sanofi. D. Russell-Jones: Other Relationship; Self; AstraZeneca, Boehringer Ingelheim, Cellnovo, Eli Lilly and Company, Novartis, Novo Nordisk, Sanofi.
Metoclopramide Restores the Sympathoadrenal Response to Hypoglycemia in a Novel Model of HAAF
Authors: VIEIRA DE ABREU ADRIANA , AGRAWAL RAHUL , HOWE PARKER , FISHER SIMON J. 
Published: June 2018

We sought to develop a novel animal model of hypoglycemia-associated autonomic failure (HAAF) and investigate the pathological process involved. We previously noted that recurrent 2-deoxyglucose (R2DG) administration induced hypoglycemia unawareness (indicated by a blunted food intake response to hypoglycemia). We now evaluate whether R2DG also induces an impaired counterregulatory response and whether this pathological process is mediated by dopaminergic receptor activation. Sprague-Dawley rats were randomized to one of three, 3-day treatments: 1) recurrent saline (Control), 2) R2DG (200 mg/kg/d, SQ), or 3) R2DG and antecedent pretreatment with the dopaminergic antagonist metoclopramide (R2DG+Meto, 3 mg/kg/d, IP). On the fourth day, all rats underwent hyperinsulinemic (50 mU/kg/min) hypoglycemic (∼50 mg/dl) clamps. Notably, recurrent 2DG abrogated the epinephrine response to hypoglycemia as compared to controls. In addition to restoring hypoglycemia awareness (i.e., the food intake response to hypoglycemia), metoclopramide normalized the epinephrine response to hypoglycemia in 2DG treated rats. Glucagon showed a similar pattern of suppression with R2DG and restoration with R2DG+Meto. In this model of HAAF, our data identifies a novel role of dopaminergic receptor activation in the development of HAAF and a potential role for metoclopramide as a potential therapeutic agent to prevent HAAF.

Disclosure
A. Vieira de Abreu: None. R. Agrawal: None. P. Howe: None. S.J. Fisher: None.
The Effect of Age on Short-Term Insulin Intensive Therapy for Patients with New Diagnosis Type 2 Diabetes
Authors: WAN XUESI , HUANG ZHIMIN , XU LIJUAN , LI YANBING 
Published: June 2018

According to our previous study, short-term intensive insulin therapies by CSII can improve β-cell function by eliminating glucotoxicity in newly diagnosed patients. It's interesting that young patients seems to recover better than old patients. The purpose of this study is to clarify the effect and mechanism of age on T2DM remission from short-term intensive insulin therapies. An observation of 160 patients with newly diagnosed T2DM (n=160, 103 male, aged 50±10 ys,HbA1C 11±2.1%) after 2-week therapy was studied remission rate. They were divided to young group (age&lt;50ys)(n=77) and old group (n=83). After 1-year of the termination of intensive therapy, there are obviously more remission patients in the young group than the old group (57/77 vs. 48/83, p&lt;0.05). As the Table showed below, the young have statistically lower FPG, Cholesterol, LDL-C, Free Fatty Acid and better HOMA-B just after therapy (p&lt;0.05). These results indicated that age might affect the remission rate mainly by the better improved metabolism of both glucose and lipids. Moreover, the results of HOMA-B has shown that younger will be easier to recover beta cell function.Young gruop at baselineYoung gruop after therapyOld group at base lineOld group after therapyFPG (mmol/L)11.84±0.356.±0.1311.79±0.366.73 ±0.18Cholesterol (mmol/L)5.69 ±0.145.04 ±0.16.±0.135.73 ±0.12HDL-C (mmol/L)1.±0.031.21 ±0.031.18 ±0.031.25 ±0.03LDL-C (mmol/L)3.81 ±0.133.36 ±0.104.±0.133.87 ±0.10Free Fatty Acid (mEq/L)0.59 ±0.020.50±0.030.68 ±0.050.61 ±0.04HOMA-β22.37±1.7775.02±6.6225.13±2.2656.38±3.85HOMA-IR3.99 ±0.272.12 ±0.154.02 ±0.272.24 ±0.12

Disclosure
X. Wan: None. Z. Huang: None. L. Xu: None. Y. Li: None.
Results of an Interim Analysis of a Phase 2, Randomized, Double-Blind, Placebo-Controlled Clinical Trial of ZGN-1061 in Patients with Obesity and Type 2 Diabetes
Authors: KIM TERRI , ZHUANG DONGLIANG , HUGHES THOMAS E. , KIM DENNIS D. , TAYLOR KRISTIN 
Published: June 2018

ZGN-1061 (1061) is a methionine aminopeptidase 2 (MetAP2) inhibitor being developed to improve glycemic control in type 2 diabetes. This clinical trial investigated the effect of 12 weeks of subcutaneous (SC) 1061 (0.05, 0.3, 0.9 mg or placebo) administered every 3 days on A1C, safety, and tolerability. Stable noninsulin diabetes therapy was permitted. The study included 129 patients; an interim analysis was conducted on a subset of patients at week 8. Baseline characteristics of the interim ITT population (N=57): 54% male, 77% white, (mean±SD) age 54±8 years, A1C 8.7±1.0%, BMI 37.2±6.4 kg/m2. At week 8, the LS mean±SE change in A1C for placebo was 0.2±0.1% (N=13) vs. -0.4±0.2% with 0.9 mg 1061 (N=13, LS mean±SE difference -0.6±0.2%, p&lt;0.02). In patients with week 12 measurements, the change in A1C was 0.4±0.2 (N=12) vs. -0.5±0.2 (N=8, difference -0.9±0.3, p&lt;0.01). There were trends for weight loss and improved fasting plasma glucose with 0.9 mg 1061 vs. placebo as well as improvements in biomarkers, including hsCRP (week 8 -2.1±2.2 mg/L vs. 1.0±2.1, ns), adiponectin (1.0±0.3 ug/mL vs. -0.1±0.3, p&lt;0.05), leptin (-6.9±1.9 ng/mL vs. 2.1±1.7, p&lt;0.05), FGF-21 (0.026±0.014 ng/mL vs. 0.000±0.013; ns), and postprandial glucose AUC (p&lt;0.01). Improvements in efficacy measures with the lower doses of 1061 were variable. There were no serious or severe adverse events (AEs) and no subjects withdrew due to an AE. The most common AE (1061&gt;placebo) was upper respiratory tract infection. The 1061 pharmacokinetic profile indicated that exposure was within target levels for efficacy and safety and there were no changes in thrombosis markers (e.g., D-dimer). In this interim analysis, 1061 produced improvements in glycemic control and metabolic biomarkers consistent with MetAP2 inhibition. 1061 was also well tolerated with no safety signals in all doses tested. Week 12 results from the full analysis dataset will be presented.

Disclosure
T. Kim: Employee; Self; Zafgen. D. Zhuang: Employee; Self; Zafgen. T.E. Hughes: Board Member; Self; Zafgen. Employee; Self; Zafgen. Stock/Shareholder; Self; Zafgen. D.D. Kim: Employee; Self; Zafgen. K. Taylor: Employee; Self; Zafgen.