bluuebunny/crossref_metadata_2025_split huggingface dataset:
1010-P: Effects of MEDI0382, an Oxyntomodulin-Like Peptide with Targeted GLP-1/Glucagon Receptor Activity, on Amino Acids, Ketones, and Free Fatty Acids
Authors: PARKER VICTORIA E. , ROBERTSON DARREN , WANG TAO , HORNIGOLD DAVID C. , POSCH MAXIMILIAN G. , PLUM-MOERSCHEL LEONA , MEIER JURIS J. , SCHLICHTHAAR HEIKE , KLAUS BEATE M. , JERMUTUS LUTZ , AMBERY PHILIP , HIRSHBERG BOAZ 
Published: June 2019

Background: MEDI0382 is an oxyntomodulin-like peptide with targeted GLP-1/glucagon receptor activity under development for type 2 diabetes mellitus (T2DM). GLP-1 has been shown to promote glucose-dependent insulin release, delay gastric emptying, and suppress appetite. Glucagon has similar effects on appetite and gastric emptying and enhances energy expenditure by upregulating energy-expensive processes such as gluconeogenesis and fatty acid oxidation.
Methods: This exploratory component of a phase 2a study measured fasting amino acid, β-hydroxybutyrate, and free fatty acid levels in overweight or obese T2DM patients randomized to once-daily SC MEDI0382 (n = 26) or placebo (n = 13) for 49 days. Doses were up-titrated weekly from 50 to 300 µg; measurements were taken at baseline and after 49 days of dosing.
Results: A significant decrease from baseline to day 49 with MEDI0382 vs. placebo in alanine was observed (-0.5 vs. 0.4 mg/dL; P = 0.017). Numerical reductions in other amino acid levels, including glutamate, cystine, valine, lysine, and tyrosine, were also seen. There were no clinically or statistically significant changes from baseline to day 49 between treatment groups in β-hydroxybutyrate or free fatty acid levels.
Conclusion: Despite the known effects of glucagon on fatty acid oxidation, MEDI0382 had no effect on ketogenesis or free fatty acids. Although the reason for this is unclear, enhanced insulin secretion may have counter-regulated this effect. MEDI0382 did promote reductions in key glucogenic amino acids, and this reduction could be related to increased gluconeogenesis and therefore glucagon receptor engagement. Similar patterns of amino acid reduction have been observed after bariatric surgery and have been attributed to excess circulating glucagon. We postulate that upregulation of an energy-consuming process such as gluconeogenesis could contribute to significant weight loss in subjects dosed with MEDI0382.

Disclosure
V.E. Parker: Employee; Self; MedImmune. Stock/Shareholder; Self; AstraZeneca. D. Robertson: Employee; Self; AstraZeneca. Employee; Spouse/Partner; GlaxoSmithKline plc. Stock/Shareholder; Self; AstraZeneca. T. Wang: Employee; Self; MedImmune. D.C. Hornigold: Employee; Self; AstraZeneca. Stock/Shareholder; Self; AstraZeneca. M.G. Posch: None. L. Plum-Moerschel: None. J.J. Meier: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Merck Sharp & Dohme Corp., Novo Nordisk A/S, Sanofi. H. Schlichthaar: None. B.M. Klaus: None. L. Jermutus: Employee; Self; AstraZeneca. Stock/Shareholder; Self; AstraZeneca. P. Ambery: Employee; Self; AstraZeneca. B. Hirshberg: Employee; Self; AstraZeneca.

Funding
AstraZeneca
1011-P: Therapeutic Potential of Novel Combination of a Long-Acting Glucagon Analog (HM15136) and Antidiabetic Drugs for the Treatment of Obesity
Authors: PARK YOUNG JIN , LEE JONG SUK , KIM JUNG KUK , KIM DAEJIN , KIM YOUNG HOON , IN YOUNG CHOI 
Published: June 2019

The obesity epidemic represents a major challenge for public health. However, existing anti-obesity drugs have limited efficacy because they only suppress appetite, emphasizing the development of next generation therapeutic option. Recently, we showed that prolonged glucagon (GCG) receptor activation with HM15136, a long-acting GCG analog, could provide potent body weight loss (BWL) in obese animal models. Considering the stimulatory effect of GCG on glucose production, transient blood glucose (BG) elevation might be important when utilizing HM15136 as a novel anti-obesity drug. Antidiabetic drugs such as metformin, and DPP-4 inhibitor have been widely used for T2DM patients. Considering their safety profile and treatment adherence in addition to BG lowering nature, we hypothesized that combination of antidiabetic drugs might minimize the transient BG elevation by HM15136 and confer additional BWL. To investigate this hypothesis, the present study evaluated the combination effect of HM15136 and antidiabetic medication on BG and BW in vivo. In normal mice, HM15136-induced BG increase was effectively reversed by concomitant treatment of metformin, sitagliptin, or empagliflozin. To further confirm, DIO mice were chronically administered with HM15136 and/or antidiabetic drugs, and normal BG control was continuously maintained in COMBO groups. These results indicate that when combined, antidiabetic drugs could effectively counteract the transient BG elevation by HM15136. As to the BWL efficacy, combination of HM15136 either with metformin, sitagliptin, or empagliflozin provided additional BWL (-18% to -31% by metformin COMBO; -35% to -47% by sitagliptin COMBO; -35% to -40% by empagliflozin COMBO), highlighting the therapeutic benefit of this novel combination.
In conclusion, our results demonstrate the prolonged GCG receptor stimulation with antidiabetic medication as a novel therapeutic option for obesity treatment.

Disclosure
Y. Park: None. J. Lee: None. J. Kim: None. D. Kim: None. Y. Kim: None. I. Choi: Employee; Self; Hanmi Pharm. Co., Ltd.
1012-P: The Factors Influencing the Changes of Adipocytokines in Patients with Newly Diagnosed T2DM Treated with Exenatide
Authors: DENG HONG RONG , XU WEN , YANG XUBIN , ZENG LONGYI , YAO BIN , WENG JIANPING 
Published: June 2019

Background: Previous studies found that adipocytokines could be altered by exenatide in patients with newly diagnosed T2DM. Whether the changes of the metabolic indices induced by exenatide have impacts on adipocytokines is still unclear. Thus, this study aimed to investigate the factors influencing the changes of leptin and adiponectin, two important adipocytokines in the pathogenesis of T2DM, in patients with newly diagnosed T2DM treated with exenatide.
Methods: In this multicenter prospective study, drug-naive patients with newly diagnosed T2DM were treated with exenatide for 48 weeks. The anthropometric data, HbA1c, β-cell function, insulin resistance, leptin, and adiponectin were assessed at baseline and at the end of the study.
Results: One hundred and ten patients completed the study. HbA1c, HOMA-IR and acute insulin response were improved significantly (P&lt;0.001). Body weight and body mass index (BMI) were significantly reduced (P&lt;0.001). Adiponectin significantly increased [5613(3353∼8352) to 7774 (4350∼12207) ng/ml, median(interquartile), P&lt;0.001], while leptin non-significantly increased [3308(1528∼5138) to 3395(1480∼5076) pg/ml, P=0.401]. The change of leptin [∆leptin: 160 (-486∼1226) pg/ml] was significantly correlated with the change of BMI and weight [∆BMI: -1.1(-2.0∼-0.4) kg/m2, r= 0.4, P=0.02; ∆weight: -3.0 (-5.7∼-1.0) kg, r=0.3, P=0.03, respectively]. ∆adiponectin was correlated with the change of HOMA-B (r= -0.4, P=0.04), but not with ∆BMI or ∆weight. Multiple linear regression using the anthropometric data or laboratory indices as independent variables and ∆leptin and ∆adiponectin as dependent variables showed that ∆leptin was independently associated with ∆weight (B= 380.8, 95% CI: 34.3∼ 727.3, P=0.032) after adjusting for the change of HbA1c, while ∆adiponectin was not.
Conclusions: The change of leptin might be influenced by the weight loss but not the hypoglycemic effect induced by exenatide in newly diagnosed T2DM.

Disclosure
H.R. Deng: None. W. Xu: None. X. Yang: None. L. Zeng: None. B. Yao: None. J. Weng: None.

Funding
National Natural Science Foundation of China (81770821 to W.X.)
1022-P: Quantitative and Qualitative Effect of Dulaglutide in Type 2 Diabetes Patients Under Treatment with Liraglutide
Authors: SOTIROPOULOS ALEXIOS , KOUTSOVASILIS ANASTASIOS , ANTONIOU ANASTASIA , BOUSBOULAS STAVROS , PEPPAS THEODOROS 
Published: June 2019

Background: Liraglutide and dulaglutide are long-acting GLP-1 receptor agonists. Dulaglutide is used once a week, while liraglutide once a day.
Aim: The aim of the study was to investigate dulaglutide’s quantitative and qualitative effect in patients, who used to take liraglutide independently of their glycemic control.
Material and Methods: 124 patients in liraglutide treatment were included in the study and switched to dulaglutide. Patients were taking the same medication before study for at least 6 months. The switch to dulaglutide was made on patients with HbA1c &lt; 7% (Group A) and on patients with HbA1c &gt; 7% (Group B). Parameters of glycemic control (HbA1c, Fasting Blood Glucose -FBG) and cardiovascular risk factors were recorded, while treatment satisfaction was evaluated with the Diabetes Treatment Satisfaction Questionnaire (DTSQ). Follow-up period was 24±2 weeks.
Results: Patients’ age was 57.65±7.43 years. A reduction of HbA1c was noticed on both groups. Group B’s HbA1c was reduced on the 3 and 6 month monitoring compared to the baseline (7.78±0.93 vs. 7.26±1.09 vs. 7.05±0.93, p= 0.001) and so was Group A’s on the same monitoring times (6.52±0.82 vs. 6.33±0.96 vs. 6.05±0.77, p=0.014). Body weight was also reduced on Group B (112.26 ±18.15 vs. 109.76±22.67 vs. 106.86±19.78, p=0.048), while Group A did not show any statistically significant difference (98.39±18.15 vs. 95.54±21.18 vs. 94.76±20.66, p=0.155). No change on blood pressure was noticed on Group A (p= 0.435) and Group B (p= 0.631). Treatment satisfaction was improved as evaluated via DTSQ on both Group A (p = 0.038) and Group B (p= 0.022) with a greater improvement in Group B.
Conclusions: Switching patients from liraglutide 1.2mg to dulaglutide 1.5mg leads to a significant reduction of HbA1c even in patients with HbA1c &lt; 7% and to an improvement of the body weight in patients who have not achieved glycemic control. Patients under treatment with dulaglutide are more satisfied with their regimen.

Disclosure
A. Sotiropoulos: None. A. Koutsovasilis: None. A. Antoniou: None. S. Bousboulas: None. T. Peppas: None.
1030-P: Effect of MEDI0382 on the Pharmacodynamics and Pharmacokinetics of Warfarin or Esmolol in Healthy Volunteers
Authors: COLEMAN HUGH A. , PETRONE MARCELLA , PETROHOY THERESA M. , YANG YE , SANFORD LINDSAY J. , HANSEN LARS , FLOR ARMANDO 
Published: June 2019

MEDI0382 is an oxyntomodulin-like peptide with targeted GLP-1 and glucagon receptor activity under development for T2DM treatment. Patients with T2DM have a high risk for cardiovascular disease. In an open-label, crossover, phase 1 study (NCT03347968), we evaluated the effect of MEDI0382 (SC; titrated up to 300 µg for 25 days) on the pharmacodynamics (PD) and PK of warfarin (PO; 25 mg on day [d] 2 [warfarin alone] and d 27 [warfarin + MEDI0382]) and PD of esmolol (IV; 200 µg/kg/min for 90 min on d 1 [esmolol alone] and d 26 [esmolol + MEDI0382]) in healthy volunteers (N = 22). Coprimary endpoints were prothrombin time (PT) maximum international normalized ratio (INRmax) and INRAUC of warfarin with MEDI0382, and change in heart rate from rest to after a 9-minute treadmill test (Bruce Protocol) with esmolol and MEDI0382. The coprimary endpoints were analyzed using paired t-tests. INRmax and INRAUC values were log transformed for analysis. MEDI0382 had no effect on PT INRmax, INRAUC (Table), or the PK profile of warfarin. Similar changes in heart rate with the treadmill test were observed with esmolol alone or with esmolol and MEDI0382 (Table). MEDI0382 resulted in an increased incidence of nausea and vomiting. There were no serious or severe adverse events. These results support co-administration of MEDI0382 and warfarin or esmolol and do not suggest safety concerns.

Disclosure
H.A. Coleman: None. M. Petrone: Employee; Self; MedImmune. T.M. Petrohoy: None. Y. Yang: Employee; Self; MedImmune. L.J. Sanford: None. L. Hansen: Employee; Self; AstraZeneca, MedImmune. Stock/Shareholder; Self; Bristol-Myers Squibb Company, Novo Nordisk A/S. A. Flor: Employee; Self; AstraZeneca.
1031-P: Impact of the Cardioprotective Effects of GLP-1 Agonists in the Management of Diabetes
Authors: MAHAPATRA SHAYAN S. , MILLA-MATUTE CRISTIAN , VILLABONA CARMEN V. , CARABALLO LUIS 
Published: June 2019

Introduction: Cardiovascular disease is the principal cause of mortality in the diabetic population. Diabetic-cardiomyopathy increases the risk of heart failure in diabetics independently of coronary artery disease. It is characterized by ventricular dilation, myocardial fibrosis and steatosis. ELIXA, LEADER and SUSTAIN-6 trials have shown decrease in adverse cardiac events with a particular GLP-1 agonist. The aim of this study is to analyze if GLP-1 agonist improves ventricular diastolic function after 6 months of therapy.
Methods: Under IRB approval, a retrospective chart review was performed on 107 patients. (EG). Experimental group of (53) patients received GLP-1agonist and (CG)Control group (54)patients that did not receive GLP-1agonists. Inclusion criteria were DM2, age 40-60 years, 6-months GLP-1 therapy and at least 1 baseline echocardiogram. Statistical analysis were performed for data evaluation.
Results: From the population studied, female was the most prevalent gender with 58.8%(63), the mean-age was 57±6.7y/o, and the most common ethnicity Caucasian 67.2%(72). The most prevalent GLP-1 used were; Liraglutide(26.5%), Exenatide(11.2%), Dulaglutide(6.8%) and Albiglutide(1.1%). When comparing echocardiogram parameters, we found; the ejection fraction in the EG was 58±12% at baseline vs. 57±8% at six-month, Lateral-Mitral E/e’ ratio 10.3±3.8 vs. 11.35±5.2, Septal-Mitral E/e’ 13.4±5.4 vs. 14.3±6.3 and Mitral E/a’ 1.1±0.5 vs. 1.07±0.5. When analyzing the (CG) echocardiogram parameters, we found that the Ejection fraction at baseline was 60±8% vs. 58±9% at six months, Lateral-Mitral E/e’ 11.15±5.4 vs. 11.84±5.5, Septal-Mitral E/e’ 14.5±7.2 vs. 15.73±6.6, and Mitral E/a’ 0.98±0.46 vs. 1.09±0.8. No statistically significant difference was found.
Conclusions: This analysis was unable to show that GLP-1 agonists improve diastolic function at the time frame studied. Studies with larger sample and longer follow-up should be performed for better understand these findings.

Disclosure
S.S. Mahapatra: None. C. Milla-Matute: None. C.V. Villabona: None. L. Caraballo: None.
1036-P: Closed-Loop Glucose Control System for In-Hospital Use: Extended Control Trials
Authors: HASHEMI NASSEH , VALK TIMOTHY , HOULIND KIM , EJSKJAER NIELS 
Published: June 2019

Background: Optimal in-hospital glucose control is a requirement for reducing mortality, morbidity and duration of admission. Present glucose concentrations in critical care are characterized by marked variability and episodes of hypoglycemia due to inadequate sensing and treatment technologies. We have previously shown (ADA 2016), that a prototype closed loop system (Admetsys™) infusing insulin/dextrose is capable of controlling blood glucose.
Aim: The aim of this study was to assess the ability of the Admetsys™ Insulin Based Infusion Systems (IBIS) (totally closed loop system) to lower, stabilize and maintain desired glucose levels and to avoid episodes of hypoglycemia for an extended period of time of up to 24 hours in patients “during admission to hospital.”
Methodology: 12 people with diabetes (ten with type 1 diabetes, two with type 2 diabetes) ranging from 26-49 years of age were admitted to our clinical research unit. The duration of the study was up to 24 hours, and at beginning of the study blood glucose levels were betwee 150 and 300 mg/dl. Through a three-way connector the Admetsys™ IBIS was connected to insulin and glucose/dextrose pumps and linked to an intravenous automated glucose sensor (VIA Glucoscout), which sent the data to the treatment system. A saline solution was infused to insure vein patency. The therapeutic target range was set to 80-125 mg/dl.
Results: Results from all twelve subjects were collected and analyzed. Mean time to reach the normoglycemic target range (80-125 mg/dl) was 2.36 hours. When target range was achieved the mean blood glucose level was 107.0 mg/dl (SD 8.6 mg/dl). No incidence of hypoglycemia (&lt;70 mg/dl) occurred during the course of the trial.
Conclusion: The Admetsys™ IBIS system proved accurate, safe and reliable in this study. However, further studies in greater patient populations are needed to validate the full performance of this closed loop system designed for hospital use.

Disclosure
N. Hashemi: None. T. Valk: Other Relationship; Self; Admetsys. K. Houlind: None. N. Ejskjaer: None.
1040-P: Evaluation of a Medtronic Enhanced Hybrid Closed-Loop (e-HCL) System during Unannounced Meals of Medium Size
Authors: ROY ANIRBAN , GROSMAN BENYAMIN , PARIKH NEHA , WU DI , LINTEREUR LOUIS J. , KURTZ NATALIE , KAUFMAN FRANCINE R. 
Published: June 2019

Background: Forgetting a premeal bolus can lead to hyperglycemia in patients with type 1 diabetes (T1D). A prototype e-HCL system was designed to automatically deliver basal insulin and correction boluses based on sensor glucose (SG) values. The effect of the system on hyperglycemia due to unannounced medium-sized meals was assessed.
Methods: Twelve subjects with T1D aged 15-25 years (median 17 years) underwent a 1-week hotel phase of e-HCL Auto Mode use, followed by a 3-week unsupervised at-home phase of use. On the third day of the hotel phase, a ∼40gm-carbohydrate (carb) dinner was consumed without a premeal bolus. Five hours of postprandial data were analyzed and compared to data captured after 40gm-carb meals eaten during the at-home phase, but accompanied by a premeal bolus.
Results: Meals without a premeal bolus resulted in postprandial SG levels statistically similar to those observed for meals accompanied by a premeal bolus (Table).
Conclusion: These data suggest that e-HCL can handle unannounced medium-sized meals to a similar extent as meals of equal size accompanied by premeal boluses. This may improve overall glycemic control of patients who underestimate or frequently forget to administer premeal boluses.

Disclosure
A. Roy: Employee; Self; Medtronic MiniMed, Inc. B. Grosman: Employee; Self; Medtronic. N. Parikh: None. D. Wu: None. L.J. Lintereur: Employee; Self; Medtronic MiniMed, Inc. N. Kurtz: Employee; Self; Medtronic MiniMed, Inc. F.R. Kaufman: Employee; Self; Medtronic.
1042-P: Real-World Treatment Patterns and Glycemic Profiles of 1,217 Adults with Type 2 Diabetes Using the Omnipod® Insulin Management System with Cloud-Based Data Management
Authors: LAYNE JENNIFER E. , JANTZ JAY , HE JIALUN , ZHENG YIBIN , BENJAMIN ERIC , LY TRANG T. 
Published: June 2019

Continuous subcutaneous insulin infusion may help optimize therapy in patients with type 2 diabetes, however, there is little real-world data on pump use in this population. This observational study characterized treatment patterns and glycemic profiles of a large cohort of adults with type 2 diabetes using a tubeless insulin pump (Omnipod® Insulin Management System, Acton, MA) with integrated blood glucose (BG) meter (Abbott Diabetes Care Inc., Alameda, CA) and data management system (Glooko, Mountain View, CA). From January 2015 through September 2018, usage data from the pump system were uploaded to the data management system and matched via device serial number to a second database of self-reported demographic data and de-identified. BG and insulin data from ≥3 mo of system use per patient were analyzed. Glycemic outcomes included mean glucose, estimated A1C and percent time in range 70-180, &lt;70 and &gt; 180 mg/dL. Patients (n=1,217) were age (mean±SD) 56.8±10.8y, 50% female and 58% used a tubeless insulin pump for ≥1 y. Glycemic profile included BG 174±39 mg/dL, estimated A1C 7.7%, time in range 70-180, &lt;70 and &gt;180 mg/dL: 57.8%±20.1, 3.2%±3.9, 39.0%±20.6, respectively. The total daily insulin was 58.3±26.5 U/d delivered as 60% basal/40% bolus with an average of 3.4±1.7 bolus deliveries per day and mean bolus amount of 7.0±3.9 U. CGM was used by 5.5% of the cohort for &gt;50% of overall time of system use. These real-world data characterizing a large cohort of adults with type 2 diabetes provide insight to self-management patterns and glycemic profiles indicating that use of tubeless insulin pump was associated with glycemic control that exceeds U.S. National Healthcare Effectiveness Data and Information Set (HEDIS) standards for adequate diabetes control.

Disclosure
J.E. Layne: Employee; Self; Insulet Corporation. J. Jantz: Employee; Self; Insulet Corporation. Employee; Spouse/Partner; Insulet Corporation. J. He: Employee; Self; Insulet Corporation. Y. Zheng: Employee; Self; Insulet Corporation. Stock/Shareholder; Self; Insulet Corporation. E. Benjamin: Employee; Self; Insulet Corporation. T.T. Ly: Employee; Self; Insulet Corporation.

Funding
Insulet Corporation
105-LB: Does HbA1c Accurately Predict Time-in-Range?
Authors: DIXON RONALD F. , MILLER DAVID P. , MAJITHIA AMIT , LEE AMY ARMENTO , ROBERTSON SCOTT , GERMANOS MARY JO , ZISSER HOWARD 
Published: June 2019

Background: Onduo’s Virtual Diabetes Clinic (VDC) incorporates a continuous glucose monitor (CGM), telemedicine, and a coaching app into the management of patients with type 2 diabetes (T2D). A recent meta-analysis of studies involving CGMs (Vigersky & McMahon 2019) showed HbA1c and time in range (%TIR) are strongly correlated.
Methods: All patients in the program with CGM usage in the 45 days prior to a follow-up HbA1c were analyzed. Mean HbA1c and %TIR were added to the previously published meta-analysis plot where each study or cohort is represented by a single dot. Additionally, a regression model was fit on the patient-level data.
Results: Patient-level results from the VDC confirm the two metrics are strongly correlated (r=.-78). At the population-level, a mean %TIR of 84% in 194 VDC patients with mean HbA1c of 7.0% is 18% higher than predicted from the meta-analysis regression line. Cohorts associated with the 3 T2D studies in the meta-analysis were the 3 with the highest %TIR versus predicted, and 1 study with mixed type 1/2 was also higher than predicted.
Conclusions: Our findings add support to the strong correlation observed between TIR and A1c overall, and suggest potentially distinct calibrations in T1D vs. T2D populations. Additional CGM data in T2D will clarify if separate prediction formulae are necessary.

Disclosure
R.F. Dixon: Employee; Self; Onduo LLC. D.P. Miller: Employee; Self; Verily Life Sciences LLC. Stock/Shareholder; Self; Verily Life Sciences LLC. A. Majithia: Consultant; Self; Onduo LLC. A. Armento Lee: Employee; Self; Verily Life Sciences LLC. S. Robertson: Employee; Self; Verily Life Sciences LLC. M. Germanos: None. H. Zisser: Employee; Self; Verily Life Sciences LLC. Stock/Shareholder; Self; Verily Life Sciences LLC.