bluuebunny/crossref_metadata_2025_split huggingface dataset:
ZGN-1061 Improves Metabolic Parameters and Hepatic Pathology in an Obese Mouse Model of Diet-Induced and Biopsy-Confirmed Nonalcoholic Steatohepatitis
Authors: BURKEY BRYAN F. , ILLEMANN MARTIN , VEIDAL SANNE , FEIGH MICHAEL , VATH JAMES , HUGHES THOMAS E. 
Published: June 2018

ZGN-1061 (1061) is a methionine aminopeptidase 2 (MetAP2) inhibitor being developed to improve glycemic control in type 2 diabetes. In diet-induced obese mice, 1061 reduces fat mass and improves glycemic control, lipid metabolism, and other metabolic parameters. This study investigated 8 weeks of treatment with 1061 (0.3 mg/kg, SC, N=11) or vehicle (N=10) on metabolic parameters, hepatic pathology, and nonalcoholic fatty liver disease (NAFLD) activity score (NAS; composite measure of steatosis, inflammation, and ballooning degeneration; range 0-8) in male mice with diet-induced and biopsy-confirmed nonalcoholic steatohepatitis (DIO-NASH). At week 8, there was a vehicle corrected weight loss of 13.1% with 1061 (p&lt;0.001). 1061-treated mice had reduced liver weight (mean±SE: 2.6±0.4 g) vs. vehicle (3.8±0.8 g, p&lt;0.001) and 21% reduction of liver triglyceride (p&lt;0.05). There was no change in food intake. NAS was unchanged in vehicle-treated mice (BL 6.2±0.1, Wk8 6.4±0.2, ns). 1061-treated mice had reduced NAS (BL 6.2±0.2, Wk8 5.0±0.3, p=0.002). Two of the NAS component measures improved: steatosis in vehicle-treated mice was unchanged (BL 3.0±0.0, Wk8 3.0±0.0, ns), whereas ZGN-1061 reduced steatosis (BL 2.9±0.1, Wk8 2.5±0.2, p=0.02), and hepatocellular ballooning was unaffected in vehicle-treated mice (BL 0.7±0.2, Wk8 0.6±0.2, ns), whereas 1061 significantly reduced ballooning severity (BL 0.6 ± 0.2, Wk8 0.0 ± 0.0, p=0.006). There was no treatment effect on fibrosis stage or liver collagen 1A. However, liver galectin-3 was reduced with 1061 vs. vehicle. 1061 produced a reduction in terminal plasma ALT and AST vs. vehicle. In DIO-NASH mice, 1061 markedly reduced body weight in conjunction with liver weight and triglyceride content. Importantly, 1061 improved liver function, steatohepatitis and NAS composite score. These findings introduce 1061 as a promising therapy for obesity-related NASH.

Disclosure
B.F. Burkey: Employee; Self; Zafgen. M. Illemann: None. S. Veidal: None. M. Feigh: None. J. Vath: Employee; Self; Zafgen. Stock/Shareholder; Self; Zafgen. T.E. Hughes: Board Member; Self; Zafgen. Employee; Self; Zafgen. Stock/Shareholder; Self; Zafgen.
MEDI0382, a GLP-1/Glucagon Receptor Dual Agonist, in Patients with Type 2 Diabetes—A Multiple-Ascending-Dose Study
Authors: ROBERTSON DARREN , STUMVOLL MICHAEL W , POSCH MAXIMILIAN G , HEISE TIM , PLUM-MOERSCHEL LEONA , KLEIN GERNOT , TSAI LAN-FENG , PETRONE MARCELLA , HIRSHBERG BOAZ , RONDINONE CRISTINA , PARKER VICTORIA E , JERMUTUS LUTZ , AMBERY PHILIP 
Published: June 2018

MEDI0382 is a GLP-1/glucagon receptor dual agonist under development for the treatment of type 2 diabetes mellitus (T2DM). This double-blind study (NCT02548585) evaluated MEDI0382 in T2DM patients with BMI 27-40 kg/m2. Subjects (n = 61) were randomized to once-daily subcutaneous MEDI0382 or placebo (PBO) at different dosing levels and uptitration schedules (100 μg [C1], 150 μg [C2], 200 μg [C3], and 300 μg (2 uptitration schedules, C4 and C5). Marked reduction in fasting and postprandial glucose was achieved with a ∼40% decrease in glucose AUC0-4h after mixed-meal testing across all cohorts (P ≤ 0.0102) (Figure 1A). Weight loss was observed at all dose levels and reached statistical significance (P = 0.024) at 300 μg (C4) (Figure 1B). Ambulatory systolic blood pressure decreased nonsignificantly from baseline in the 300-μg cohort (C4, -4.9 vs. -6.5 mmHg; C5, -9.1 vs. -5.0 mmHg). Similar to other marketed GLP-1 analogs, MEDI0382 increased pulse rate vs. PBO (C4, 8.4 vs. -2.4 BPM, P = 0.0039; C5, 5.8 vs. 0.2 BPM, P = 0.0796). Treatment-related adverse events occurred more often with MEDI0382 vs. PBO (86% [36/42] vs. 47% [9/19]); most events were mild or moderate in severity.
In conclusion, MEDI0382 administered for up to 22 days showed a marked reduction in both fasting and postprandial glucose with weight reduction and an acceptable tolerability profile.

Disclosure
D. Robertson: Employee; Self; MedImmune. Employee; Spouse/Partner; GlaxoSmithKline plc. M.W. Stumvoll: Speaker's Bureau; Self; Novartis Pharmaceuticals Corporation. Advisory Panel; Self; AstraZeneca, Novo Nordisk A/S. Speaker's Bureau; Self; Merck Foundation. M.G. Posch: 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. L. Plum-Moerschel: None. G. Klein: None. L. Tsai: Employee; Self; MedImmune. M. Petrone: Employee; Self; MedImmune. Stock/Shareholder; Self; MedImmune. B. Hirshberg: Employee; Self; AstraZeneca, MedImmune. C. Rondinone: Employee; Self; MedImmune. Stock/Shareholder; Self; AstraZeneca, F. Hoffmann-La Roche Ltd., Abbott, AbbVie Inc. V.E. Parker: Employee; Self; MedImmune. Stock/Shareholder; Self; Accenture. Employee; Self; AstraZeneca. L. Jermutus: Employee; Self; AstraZeneca. Stock/Shareholder; Self; AstraZeneca. P. Ambery: Employee; Self; MedImmune. Stock/Shareholder; Self; AstraZeneca.
Short Duration of Diabetes Should Be Associated with More Prominent Effect of Liraglutide—Titrated from Insulin Degludec plus Liraglutide Combination Therapy
Authors: KASHIMA KOJI , SHIMIZU HIROYUKI , YAMADA MASANOBU 
Published: June 2018

Objective: In management of type 2 diabetes (T2DM), controlling HbA1c &lt;7% is required. We examined effectiveness of insulin degludec (DEG) plus liraglutide (LIRA) combination therapy in Japanese T2DM patients.
Methods: Hospitalized hyperglycemic 55 patients with T2DM who started this therapy were randomly recruited. Changes of HbA1c, Insulin doses, and ADRR in patients who did self-blood glucose monitoring (SMBG) were evaluated for a year after discharge. Since preserved β-cell function might influence the effect, effectiveness was compared by duration of T2DM ≤ 5 year (n=27) or ≥ 6 year (n=28).
Results: 1) Baseline characteristics: Patients with short duration (SHORT) were younger (62±9.5 vs. 69.9±11.8 years old: p&lt;0.05), had shorter duration (0.44±1.3 vs. 17.1±9.3 year:p&lt;0.01), higher urinary C-peptide (91.1±4.6 vs. 47.0±30μg/day: p&lt;0.01), higher HbA1c (12.4±2.5 vs. 11.0±2.3%: p&lt;0.05), and lower final dose of liraglutide (0.68±0.18 vs. 0.78±0.17mg/day: p&lt;0.05) compared with long duration (LONG) group. 2) Mean HbA1c in 55 patients have reached the target from 3rd month to 12th month. 3) Although daily glucose excursions at discharge and mean body weight were identical throughout a year in 2 groups, HbA1c in SHORT group dramatically improved after discharge. The average of HbA1c was maintained ≤ 6.0% from 4th month to 12th month. 4) Patients with HbA1c ≤ 6.0% using SMBG showed lower ADRR scores (1∼9). 5) The combined use of DEG and its dose gradually decreased in SHORT group, one third of patients could quit DEG at 6th month and over half at 12th month, but none in LONG group. 6) Although Long group had higher rates of chronic kidney disease (CKD) 46.4% and ischemic heart disease (IHD) 28.5%, SHORT group still had high rates of CKD 22.2% and IHD 18.5%.
Conclusion: Since T2DM is a complex metabolic disorder, prominent effect of LIRA in the patients with short duration is supportive for GLP-1 receptor agonists as a first-line therapy.

Disclosure
K. Kashima: None. H. Shimizu: Speaker's Bureau; Self; Eli Lilly and Company, MSD K.K., Daiichi Sankyo Company, Limited, Nippon Boehringer Ingelheim Co. Ltd., Novo Nordisk Inc.. M. Yamada: None.
Medication Compliance on Glycemic Control in Patients with Elevated HbA1c
Authors: ELHASSAN AHMED , ABREU MARCONI , TUMYAN ANNA , PAPACOSTEA OLIVIA , PEICHER KATHERINE , DIMACHKIE PERIHAN , SIDDIQUI MUHAMMAD S. , ADAMS-HUET BEVERLEY , LI XILONG , POP LAURENTIU , LINGVAY ILDIKO 
Published: June 2018

The SIMPLE study was a randomized trial comparing two treatment strategies [basal insulin (BI) + GLP-1 RA vs. basal-bolus insulin (BBI)] in patients with T2DM and very elevated HbA1c (&gt;10%). The glucose lowering agents were provided free of charge for the 6-month study. This post-hoc analysis evaluates compliance with the assigned glucose lowering agents, and the effect of compliance on glycemic control. Compliance was assessed by inventory of the returned medication. Optimal compliance was defined as &gt;80% use of the respective agent over the entire duration of the study. Mixed model repeated measures analysis with compliance as a covariate was used to evaluate the treatment effect on HbA1c.
The 120 randomized patients had a mean (SD) age 47.4 (9.5) years, BMI 37.2 (10.3) kg/m2, and baseline HbA1c 12.1 (1.4)%. The proportion of patients with optimal compliance with basal insulin was numerically higher in the BI+GLP-1 RA vs. BBI group (p=0.16); optimal compliance with GLP-1 RA was higher compared to bolus insulin (p=0.04) (Table). Compliance was an independent predictor for glycemic improvement (P = 0.008); treatment with BI+GLP-1 RA was superior at lowering HbA1c after adjustment for compliance (P = 0.01).
Optimal compliance was low in this patient population. While compliance was a significant contributor to glycemic control, treatment with BI+GLP-1 RA improved HbA1c more than BBI independent of medication compliance.Table. Patients with optimal compliance with glucose lowering agents (&gt;80% over the 6-month study duration) in the two treatment groups (basal insulin + GLP1 RA compared with basal-bolus insulin) and the effect of compliance on glycemic control.Basal-Bolus Insulin Group(BBI, n=56a)Basal Insulin + GLP1 RA Group (BI+GLP1 RA, n=54a)Patients with optimal compliance:Basal Insulin8 (14.3)14 (25.9)Bolus Insulin6 (10.7)NAGLP1 RANA14 (25.9)Change in HbA1c:Adjusted for compliance- 3.1 (-4.0,-2.2)- 4.5 (-5.2,-3.8)Optimal Compliance subgroup-3.2 (-4.8,-1.6)-5.4 (-6.6, -4.2)Low Compliance subgroup-3.0 (-3.7,-2.3)-3.6 (-4.4,-2.8)Data are Least squares means (95%CI) or N (%); NA - Not applicable. acompliance data available for n=110 (intention-to-treat analysis sample).

Disclosure
A. Elhassan: None. M. Abreu: None. A. Tumyan: None. O. Papacostea: None. K. Peicher: None. P. Dimachkie: None. M.S. Siddiqui: None. B. Adams-Huet: None. X. Li: None. L. Pop: None. I. Lingvay: Advisory Panel; Self; Novo Nordisk A/S, Eli Lilly and Company, AstraZeneca, Intarcia Therapeutics, Inc., Sanofi-Aventis. Research Support; Self; Novo Nordisk A/S, Merck Sharp & Dohme Corp., Pfizer Inc., GI Dynamics Inc., Novartis AG. Other Relationship; Self; Sanofi, AstraZeneca, Boehringer Ingelheim GmbH, Novo Nordisk A/S.
ZGN-1061, a Novel MetAP2 Inhibitor, and Liraglutide Combine to Improve Glycemic Control and Reduce Body Weight in a Rat Model of Diet-Induced Obesity
Authors: BURKEY BRYAN F. , PEDERSEN PHILIP J. , PEDERSEN TANJA X. , FEIGH MICHAEL , VATH JAMES , HUGHES THOMAS E. 
Published: June 2018

ZGN-1061 (1061) is a methionine aminopeptidase 2 (MetAP2) inhibitor being developed to improve glycemic control in T2D. This study investigated 5 weeks (weeks) of once-daily SC treatment with a submaximal 0.3 mg/kg dose of 1061, a maximal 0.4 mg/kg dose of liraglutide (lira), 1061+lira, or vehicle (N=10/group) on body weight (BW), food intake/preference, and glycemic control in the Gubra diet-induced obese (DIO) rat model (ad libitum fed chow and highly palatable high-fat, high-sugar [HFHS] diet). Fasting (4 hour) blood glucose (FBG) was collected weekly and a semifasted (16 hour access to 50% of daily energy requirement) OGTT was performed at week 4. At week 5 (day 33), BW changed by +1.7% with vehicle vs. -6.0% with 1061, -9.1% with lira, and -16.9% with 1061+lira (all p&lt;0.001). BW loss occurred earlier with lira (day 1) than 1061 (day 5). Starting at day 6, intake of the HFHS diet was modestly reduced (15-30%) with 1061 vs. vehicle. In contrast, lira and 1061+lira induced rapid and sustained 40-50% and 50-80% reductions in intake of the HFHS diet, respectively, over the first 8-9 days. Cumulative (day 0-35) HFHS diet intake was reduced vs. vehicle by 1061 (13.4%, p=0.07), lira (17.8%, p&lt;0.01), and 1061+lira (38.2%, p&lt;0.001). Cumulative chow intake was increased by 1061 and 1061+lira but not lira alone. There was a modest reduction in FBG (mean week 1-5) with 1061 vs. vehicle (p=0.08), a significant reduction with lira, and 1061+lira produced the largest reduction (both p&lt;0.001) that was significantly lower than either agent alone (both p&lt;0.01). In the OGTT, 1061 reduced the glucose AUC vs. vehicle by 37% (p=0.07), lira by 60% (p&lt;0.001), and 1061+lira by 80% (p&lt;0.001), achieving an AUC that was no different from lean rats. In this DIO rat model, 1061 and lira had complementary effects on reducing BW and normalizing glycemic control. Combination treatment with 1061 and liraglutide may yield greater weight loss and glycemic control than either agent alone in patients with T2D.

Disclosure
B.F. Burkey: Employee; Self; Zafgen. P.J. Pedersen: None. T.X. Pedersen: Employee; Self; Gubra. M. Feigh: None. J. Vath: Employee; Self; Zafgen. Stock/Shareholder; Self; Zafgen. T.E. Hughes: Board Member; Self; Zafgen. Employee; Self; Zafgen. Stock/Shareholder; Self; Zafgen.
LIRA-PRIME Trial Design and Baseline Data—Efficacy in Controlling Glycemia with Liraglutide in a Primary Care Setting
Authors: UNGER JEFF , LOWE DEREK , MURPHY GERRI , PANDA JAYANT KUMAR , SARGIN MEHMET , KALTOFT MARGIT , TREPPENDAHL MARIANNE , ZOGHBI MAROUAN 
Published: June 2018

Despite the majority of patients with type 2 diabetes (T2D) being treated in primary care, clinical evidence to guide treatment decisions is still scarce in this setting.
LIRA-PRIME (NCT02730377), a 104-week, randomized (1:1), open-label, active-controlled trial in primary care, compares the efficacy of liraglutide vs. oral antidiabetic drugs (chosen by the investigator) in controlling glycemia in patients with T2D inadequately controlled with metformin alone. Besides an A1C of 7.5-9.0% within 90 days prior to screening, the pragmatic approach of the trial includes few inclusion and exclusion criteria, treatment according to local labels, quarterly visits after week 26, and trial product dispensing by retail pharmacy. Primary endpoint is time to inadequate glycemic control, defined as A1C &gt;7.0% at two scheduled consecutive visits after the first 26 weeks of treatment.
The trial randomized 1997 patients from 9 countries. The broad distribution of baseline characteristics, e.g., age range of 19.0-89.0 years, reflects the study design and heterogeneity of patients treated in primary care (Table).
LIRA-PRIME will provide data-currently lacking-from primary care regarding the efficacy of liraglutide in controlling glycemia in patients with T2D inadequately controlled with metformin alone. A population with such broad baseline characteristics is well suited for this investigation.

Disclosure
J. Unger: Advisory Panel; Self; Novo Nordisk A/S, Abbott. Consultant; Self; Novo Nordisk A/S, Abbott. Research Support; Self; Novo Nordisk A/S, Janssen Pharmaceuticals, Inc., Sanofi-Aventis, Merck & Co., Inc., Abbott, Mylan. Speaker's Bureau; Self; Novo Nordisk A/S, Janssen Pharmaceuticals, Inc.. Stock/Shareholder; Self; Novo Nordisk A/S. D. Lowe: Consultant; Self; Novo Nordisk A/S. G. Murphy: None. J. Panda: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim GmbH, Sanofi, Eli Lilly Ltd.. Employee; Self; Department of Health & Family Welfare, Govt. of Odisha, India. Research Support; Self; Novo Nordisk India Ltd. M. Sargin: Speaker's Bureau; Self; Novo Nordisk A/S, AstraZeneca. M. Kaltoft: Employee; Self; Novo Nordisk A/S. M. Treppendahl: Employee; Self; Novo Nordisk A/S. Stock/Shareholder; Self; Novo Nordisk A/S. M. Zoghbi: Advisory Panel; Self; Novo Nordisk A/S. Research Support; Self; Pharmaline. Speaker's Bureau; Self; Eli Lilly and Company, Merck Sharp & Dohme Corp., Novartis AG, AstraZeneca, Novo Nordisk A/S. Advisory Panel; Spouse/Partner; AbbVie Inc., NewBridge.
Distinct Patterns of Daily Glucose Variation by Pubertal Stage in Youth with Type 1 Diabetes (T1D)
Authors: ZHU JIA , VOLKENING LISA , KATZ MICHELLE , LAFFEL LORI M. 
Published: June 2018

Background: Glucose variability is an emerging risk factor for diabetes complications. As basal insulin requirements vary in youth with T1D by age and time of day, we analyzed daily patterns of glucose variation by pubertal stage in youth with T1D.
Methods: Glucose patterns were assessed using 4 weeks of continuous glucose monitoring (CGM) data from 107 youth ages 8-17 years with T1D for &gt;1 year. Glucose values per hour were expressed as percentages relative to the mean glucose over a 24-hour period. Glucose patterns were compared by pubertal stage (pre-pubertal: Tanner (T) 1, pubertal: T2-4, post-pubertal: T5).
Results: The sample had a mean (±SD) age of 13.1±2.6 years, T1D duration of 6.3±3.5 years, A1c of 7.8±0.8; 88% were pump-treated. Pre-pubertal youth had greater mean standard deviation (86.4±12.0, p=.008) and coefficient of variation (0.43±.05, p=.04) compared to pubertal (79.8±13.4; 0.41±.05) and post-pubertal youth (75.8±13.3; 0.40±.05). There was no difference in mean glucose or A1c by pubertal stage (p &gt;.4). Patterns of glucose variation appear in Figure.
Conclusion: Pre-pubertal compared with pubertal and post-pubertal youth appear to have greater glucose variability independent of A1c, with a notable dawn-dusk pattern. Thus, A1c alone does not seem to capture the full range of glycemic parameters in youth with T1D, highlighting the added value of CGM data when determining optimal insulin doses.

Disclosure
J. Zhu: None. L. Volkening: None. M. Katz: None. L.M. Laffel: Consultant; Self; Eli Lilly and Company, Novo Nordisk Inc., Sanofi US, MannKind Corporation, Roche Diagnostics Corporation, Dexcom, Inc., Insulet Corporation, AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Johnson & Johnson Diabetes Institute, LLC..
Effect of Biased GLP-1/Glucagon Receptor Co-agonists on Insulin Secretion
Authors: FAROOQ GALA , JONES BEN , MINNION JAMES S. , BLOOM STEPHEN R. 
Published: June 2018

Introduction: The effect of dual GLP-1 and glucagon analogues on insulin secretion remains unclear. Here, we investigated the effect of novel GLP-1 / glucagon receptor (GLP-1R/GCGR) co-agonists on beta cell lines, finding augmented insulin release compared to reference agonist Exendin-4. This effect was related to signalling bias at the GLP-1R.
Methods: GLP-1R/GCGR co-agonists were designed, based on the sequence of oxyntomodulin. INS-1 832/3 beta cells and MIN6B1 beta cells were used to perform 24 hour insulin secretion assays. Ligand-directed signal bias was determined from cyclic adenosine monophosphate (cAMP) and β arrestin-1/2 responses measured by enzyme fragment complementation in CHO-K1 cells expressing GLP-1R or GCGR.
Results: Several co-agonists show enhanced maximal insulin release compared to Exendin-4 (representative co-agonist Peptide A vs. Exendin-4 fold insulin release, normalized to 11mM glucose: INS-1 823/3 cells 4.45 ± 0.24 vs. 2.55 ± 0.22, p = 0.0002; MIN6B1 cells 2.28 ± 0.22 vs. 1.57 ± 0.08, p = 0.002). At the GLP-1 receptor, co-agonists were biased towards cAMP generation, compared to the β arrestin-2 pathway (delta log (τ/KA) -0.70 ± 0.11 [Peptide A], vs. 0.29 ± 0.11 [Exendin-4], p= &lt;0.0001). At the GCGR, no significant change in bias was seen relative to native glucagon.
Conclusion: GLP-1R/GCGR co-agonists show enhanced insulin release in vitro compared to exendin-4. As canonical effects of β arrestin recruitment include desensitisation and loss of cell surface receptors via endocytosis, the observed signal bias with these peptides may be linked to their insulinotropic effect. These findings may inform the design of more potent insulinotropic compounds for therapeutic use in type 2 diabetes.

Disclosure
G. Farooq: None. B. Jones: None. J.S. Minnion: None. S.R. Bloom: None.
Exploring the Efficacy of Efpeglenatide, a Weekly Glucagon–Like Peptide–1 Receptor Agonist (GLP–1RA)–Evidence from Preclinical, Modeling, and Clinical Studies
Authors: ROSENSTOCK JULIO , TRAUTMANN MICHAEL E. , HOMPESCH MARCUS , CHOI IN YOUNG , KANG JAHOON , YOON KUN-HO , SORLI CHRISTOPHER H. 
Published: June 2018

Once-weekly (QW), subcutaneous efpeglenatide (efpeg) is a long-acting GLP–1 RA in development for type 2 diabetes (T2D). In vitro studies have shown that efpeg is a superagonist: an agent that can achieve a greater maximal effect than that of the endogenous ligand. Exploratory analyses of preclinical, modeling, and clinical data investigated the effects of efpeg on glycated hemoglobin (HbA1c) and body weight (BW) vs. dulaglutide (dula), liraglutide (lira), and semaglutide (sema) (Table). In preclinical studies, efpeg significantly reduced the increment of HbA1c vs. lira and dula in db/db mice, and reduced BW vs. dula in diet-induced obesity mice. Predictive treatment effects of GLP–1 RAs over 30 weeks (based on modeled data) suggest that efpeg 6 mg QW has a high probability of superiority vs. dula on HbA1c and BW, and similar effects on HbA1c vs. sema; 4 mg QW has a high probability of non-inferiority and superiority vs. dula on HbA1c and BW endpoints, respectively. Analyses of the EXCEED 203 dose-ranging study in T2D suggest that efpeg 4 mg QW is at least non-inferior to lira on HbA1c reduction; safety profiles and effects on BW were comparable.
In conclusion, the efficacy of efpeg in reducing HbA1c and BW is supported by preclinical, modeling, and clinical studies, providing the basis for long-term randomized trials to compare these effects vs. other GLP-1 RAs.

Disclosure
J. Rosenstock: Advisory Panel; Self; Eli Lilly and Company. Consultant; Self; Eli Lilly and Company. Research Support; Self; Novo Nordisk Inc.. Consultant; Self; Novo Nordisk Inc.. Advisory Panel; Self; Sanofi. Consultant; Self; Sanofi. Advisory Panel; Self; Janssen Pharmaceuticals, Inc.. Consultant; Self; Janssen Pharmaceuticals, Inc.. Advisory Panel; Self; Boehringer Ingelheim Pharmaceuticals, Inc.. Consultant; Self; Boehringer Ingelheim Pharmaceuticals, Inc.. Advisory Panel; Self; Intarcia Therapeutics, Inc.. Consultant; Self; Intarcia Therapeutics, Inc.. Research Support; Self; Merck & Co., Inc., Pfizer Inc., Sanofi, Novo Nordisk Inc., Bristol-Myers Squibb Company, Eli Lilly and Company, Intarcia Therapeutics, Inc., Genentech, Inc. M.E. Trautmann: Consultant; Self; ProSciento. Stock/Shareholder; Self; Eli Lilly and Company. Consultant; Self; Hanmi Pharmaceutical, CeQur Corporation, Intarcia Therapeutics, Inc., Servier. M. Hompesch: Other Relationship; Self; Hanmi Pharmaceutical. I. Choi: Employee; Self; Hanmi Pharmaceutical. Stock/Shareholder; Self; Hanmi Pharmaceutical. J. Kang: Employee; Self; Hanmi Pharmaceutical. K. Yoon: None. C.H. Sorli: Employee; Self; Sanofi.