bluuebunny/crossref_metadata_2025_split huggingface dataset:
767-P: TERN-601, a Novel Oral GLP-1R Agonist, Suppresses Food Intake and Improves Glucose Tolerance in Transgenic Mice Expressing Human GLP-1 Receptor
Authors: JONES CHRISTOPHER , QUINN KEVIN P. , NELSON CARA H. , OSBORN OLIVIA , LUEHR GARY , JASPER JEFFREY R. 
Published: June 2023

Synthetic peptide agonists of the GLP-1 receptor (GLP-1R) are approved for the treatment of diabetes and obesity based on their ability to lower blood glucose and induce weight loss. TERN-601 is a novel, oral small molecule GLP-1R agonist in preclinical development. In vitro, TERN-601 potently stimulated (EC50 = 2.9 ± 0.8 nM) intracellular cAMP generation, a downstream consequence of GLP-1R activation, in CHO-K1 cells stably expressing human GLP-1R. In vivo, single oral doses of TERN-601 (10, 30, or 60 mg/kg) led to significant dose-dependent suppression of food intake (2- to 24-hours post dose) in transgenic C57BL/6J mice (n = 10 per group) expressing human GLP-1R (hGLP-1R). In an intraperitoneal glucose tolerance test (IPGTT) on overnight fasted hGLP-1R mice (n = 7 per group), single oral doses of TERN-601 (0.3, 1, and 3 mg/kg) administered 30 minutes prior to IP glucose injection significantly lowered blood glucose area under the curve (AUC0-120min) with comparable efficacy to liraglutide (0.3 mg/kg). TERN-601 is a potent, orally bioavailable small molecule agonist of human GLP-1R in preclinical development for the treatment of chronic obesity. In transgenic mice expressing human GLP-1R, single oral doses of TERN-601 significantly suppressed food intake and improved glucose tolerance. Together these data support the continued development of TERN-601.

Disclosure
C.Jones: Employee; Terns Pharmaceuticals. K.P.Quinn: None. C.H.Nelson: Employee; Terns Pharmaceuticals, Gilead Sciences, Inc., Stock/Shareholder; Terns Pharmaceuticals, Gilead Sciences, Inc. O.Osborn: Employee; Terns, Stock/Shareholder; ClicBio. G.Luehr: None. J.R.Jasper: Advisory Panel; Rubedo Life Sciences, Employee; Terns Pharmaceuticals, Rubedo Life Sciences.
769-P: Effect of Food on the Pharmacokinetics, Safety, and Tolerability of Orforglipron (LY3502970), an Oral, Nonpeptide GLP-1 Receptor Agonist
Authors: MA XIAOSU , LIU RONG , PRATT EDWARD J. , BENSON CHARLES , BHATTACHAR SHOBHA N. 
Published: June 2023

Orforglipron [OFG (LY3502970)] is an oral, non-peptide glucagon-like peptide-1 receptor agonist (GLP-1 RA). This reports the results of 2 studies that assessed PK, safety, and tolerability of OFG in healthy subjects, fasted and fed state, after single and repeated doses.
Studies A and B were phase 1, randomized, open-label, crossover studies evaluating the effect of food on OFG concentration in healthy adults after a single 3 mg dose (study A) and after a 16 mg daily dose (study B), which was reached by weekly dose escalation starting with 2 mg.
Based on statistical analysis, Cmax was 23% (study A) and 21% (study B) lower in the fed state. AUC(0-∞), and AUC(0-24) were 24% (study A) and 18% (study B) lower when administered with food. Tmax and T1/2 were similar with or without food. In study A and B, treatment emergent adverse events (TEAEs) were mild. In study B, TEAEs occurred most often with the starting dose and decreased with dose escalation. The most common TEAEs in study B were decreased appetite (69.7%), nausea (48.5%), and vomiting (45.5%).
Overall mean exposure to OFG based on Cmax and AUC was numerically lower when administered with food and had little effect on Tmax and T1/2. Based on exposure response relationship, PK differences are unlikely to result in clinically meaningful differences in OFG safety and efficacy. Phase 3 studies are planned without food or water restrictions.

Disclosure
X.Ma: Employee; Eli Lilly and Company, Stock/Shareholder; Eli Lilly and Company. R.Liu: None. E.J.Pratt: Employee; Eli Lilly and Company. C.Benson: Employee; Eli Lilly and Company, Stock/Shareholder; Eli Lilly and Company. S.N.Bhattachar: None.
772-P: Tirzepatide vs. Basal Insulins in People with T2D and Different Baseline Glycemic Patterns—Post Hoc Analyses of the SURPASS-3 and -4 Trials
Authors: GIORGINO FRANCESCO , FRANCO DENISE R. , NICOLAY CLAUDIA , HEMMINGWAY ANDREA , RODRÍGUEZ ÁNGEL , WIESE RUSSELL 
Published: June 2023

While basal insulins act primarily by reducing fasting serum glucose (FSG), the once-weekly GIP/GLP-1 receptor agonist tirzepatide targets both FSG and postprandial glucose (PPG). This post-hoc analysis assessed the efficacy of tirzepatide vs insulin degludec (SURPASS-3) and glargine (SURPASS-4) in people with T2D and different baseline glycemic patterns. We assessed change from baseline to Week 52 in HbA1c, FSG, and PPG across subgroup categories in participants on assigned treatment without rescue medication (efficacy estimand) using mixed-model repeated measures. Four subgroups were defined by different combinations of FSG and PPG (low FSG/low PPG, low FSG/high PPG, high FSG/low PPG, high FSG/high PPG). Low and high FSG and PPG were split based on median values of these parameters in SURPASS-3 (162 and 187 mg/dL) and -4 (164 and 197 mg/dL). While reductions in FSG were generally similar between tirzepatide and the basal insulins in both studies, decreases in PPG were greater with tirzepatide in all subgroups. This resulted in greater HbA1c reductions with tirzepatide vs basal insulin in all subgroups. The extent of reduction in FSG, PPG, and HbA1c in each subgroup was related to baseline values of these parameters. These data support previous observations of superior glycemic control with TZP compared with basal insulin, irrespective of baseline FSG and PPG levels.

Disclosure
F.Giorgino: Advisory Panel; Boehringer-Ingelheim, Amarin Corporation, Medtronic, Roche Diabetes Care, Sanofi, Bayer Inc., Novo Nordisk, Consultant; Novo Nordisk, Lilly, Research Support; Lilly, Roche Diabetes Care, AlfaSigma, Speaker's Bureau; Abbott, Boehringer-Ingelheim, Lilly, Sanofi, Medscape. D.R.Franco: Advisory Panel; Abbott, Eli Lilly and Company, Medtronic, Speaker's Bureau; Eli Lilly and Company, Boehringer Ingelheim and Eli Lilly Alliance, Medtronic, Sanofi, AstraZeneca, Roche Diabetes Care, Abbott Diabetes. C.Nicolay: Employee; Eli Lilly and Company. A.Hemmingway: Employee; Eli Lilly and Company, Stock/Shareholder; Eli Lilly and Company. Á.Rodríguez: Employee; Eli Lilly and Company, Stock/Shareholder; Eli Lilly and Company. R.Wiese: Employee; Eli Lilly and Company.

Funding
Eli Lilly and Company
775-P: Predictors of Glycemic Control in Older People with Type 2 Diabetes Treated with iGlarLixi—A Pooled Analysis
Authors: MUNSHI MEDHA , RITZEL ROBERT , MCCRIMMON RORY J. , HRAMIAK IRENE , LAUAND FELIPE , MELAS-MELT LYDIE , SOUHAMI ELISABETH , ROSENSTOCK JULIO 
Published: June 2023

For older adults (&gt;65 years) with type 2 diabetes (T2D), iGlarLixi can be a simple and effective therapeutic option. We aimed to identify factors associated with achieving target HbA1c &lt;7% and derived Time in Range (dTIR) ≥70% in this population in response to once daily iGlarLixi.
This post-hoc, pooled analysis of 4 randomized trials included 465 people advancing from oral (LixiLan-O), GLP-1 RA (LixiLan-G), or insulin (LixiLan-L; SoliMix) therapies to iGlarLixi for 26 or 30 weeks. HbA1c and dTIR responses were assessed at baseline (BL) and end of treatment (EOT) for each participant and classified as attained (&lt;7.0% or dTIR ≥70%) or unattained (≥7.0% or &lt;70%). dTIR was calculated from 7-point self-monitored plasma glucose profiles from the three LixiLan studies (LixiLan-O. G, and L). Potential predictive factors were analyzed by univariable and multivariable stepwise logistic regression.
Overall, 60% of participants achieved HbA1c &lt;7.0% and 87.5% achieved dTIR ≥70%. Predictors of attained HbA1c response (p&lt;0.05) included lower BL HbA1c and lower BL insulin dose. Predictor of attained dTIR response (p&lt;0.05) was higher BL fasting plasma glucose (FPG; Table), while sex, T2D duration, and obesity had no predictive value.
To conclude, in older people with T2D treated with iGlarLixi, consideration of BL HbA1c and FPG, as well as BL insulin dose may improve achieving individualized glycemic targets.

Disclosure
M.Munshi: Consultant; Sanofi. R.Ritzel: Consultant; Novo Nordisk, Sanofi, Speaker's Bureau; Novo Nordisk, Sanofi, Pfizer Inc., Merck Sharp & Dohme Corp., Lilly. R.J.Mccrimmon: Advisory Panel; Sanofi, Speaker's Bureau; Novo Nordisk A/S. I.Hramiak: Research Support; Eli Lilly and Company, Novo Nordisk, Sanofi, Speaker's Bureau; Canadian Medical & Surgical Knowledge Translation Research Group (CMS), Insulet Corporation, Medtronic, Merck & Co., Inc., Bayer Inc. F.Lauand: Employee; Sanofi. L.Melas-melt: None. E.Souhami: Employee; Sanofi, Stock/Shareholder; Sanofi. J.Rosenstock: Advisory Panel; Applied Therapeutics Inc., Boehringer Ingelheim Inc., Eli Lilly and Company, Novo Nordisk, Oramed Pharmaceuticals, Sanofi, Zealand Pharma A/S, Intarcia Therapeutics, Inc., Hanmi Pharm. Co., Ltd., Research Support; Applied Therapeutics Inc., Boehringer Ingelheim Inc., Eli Lilly and Company, Merck & Co., Inc., Novartis, Novo Nordisk, Pfizer Inc., Sanofi, Intarcia Therapeutics, Inc.

Funding
Sanofi
776-P: Comparative Effectiveness of SC Semaglutide in Adults with T2D in U.S. Routine Clinical Practice—Year 1 Results of SEPRA, a Randomized Pragmatic Clinical Trial
Authors: BUSE JOHN B. , SOULE BENJAMIN P. , HARTY BRIAN J. , CHRISTENSEN HELENE N. , CZIRAKY MARK J. , WILLEY VINCENT , SKIBSTED SIMON 
Published: June 2023

SEPRA, a 2-year, ongoing, open-label, randomized, pragmatic study (NCT03596450) compares the effects of once-weekly SC semaglutide (sema) with physician's choice SOC when added to ≤2 oral antidiabetic medications for treatment intensification in US health-insured adults with T2D. The objective is to generate real-world evidence to support routine clinical decision making and complement clinical trial data. The primary endpoint is the proportion of patients who achieve HbA1c &lt;7% at 1 year. Patients (N=1278) were randomized to receive sema according to label (n=644) or SOC excluding sema (n=634). All other treatment was per routine clinical care. Baseline characteristics were comparable (Table 1). Most common SOC medications were other GLP-1RAs (71.3%) and SGLT2is (15.5%). Sema dosing at 1 year was 26.6% at 0.25 mg, 30.4% at 0.5 mg and 24.4% at 1 mg (10.6% ended study and 7.6% not on sema at year 1). Use of sema resulted in a significantly greater proportion of patients achieving HbA1c &lt;7% and body weight reduction vs SOC at 1 year (Table 1). A lower proportion of sema patients required additional treatment intensification in year 1 of the study vs SOC. No new safety concerns were identified. SEPRA demonstrates the superior effect of sema vs physician's choice SOC and that sema is an efficacious, durable treatment option in routine clinical practice.

Disclosure
J.B.Buse: Consultant; Alkahest, Anji Pharmaceuticals, AstraZeneca, Bayer Inc., Biomea Fusion, Inc., Boehringer Ingelheim International GmbH, CeQur SA, Cirius Therapeutics, Inc., Corcept Therapeutics, Eli Lilly and Company, GentiBio, Glycadia, Glyscend Inc., Janssen Pharmaceuticals, Inc., Mellitus Health, Pendulum Therapeutics, Praetego, LLC, Stability Health, Terns, Inc, Valo, Other Relationship; Novo Nordisk, Research Support; Dexcom, Inc., Novo Nordisk, vTv Therapeutics, Stock/Shareholder; Glyscend Inc., Mellitus Health, Pendulum Therapeutics, PhaseBio Pharmaceuticals, Inc., Praetego, LLC, Stability Health. B.P.Soule: Employee; Novo Nordisk. B.J.Harty: Research Support; Novo Nordisk. H.N.Christensen: Employee; Novo Nordisk, Stock/Shareholder; Novo Nordisk A/S. M.J.Cziraky: Other Relationship; Novo Nordisk. V.Willey: Other Relationship; Novo Nordisk A/S. S.Skibsted: Employee; Novo Nordisk A/S.

Funding
Novo Nordisk
779-P: Intensification of Glucagon-Like Peptide-1 Receptor Agonists Therapy with First and Second Generation Basal Insulins—The RESTORE-G Real-World Study
Authors: NAPOLI RAFFAELE , LAROSA MONICA , NICOLUCCI ANTONIO , CHIARA ROSSI MARIA , CANDIDO RICCARDO , STUDY GROUP RESTORE-G 
Published: June 2023

ADA guidelines suggest that in patients needing insulin treatment, combination therapy with a glucagon-like peptide 1 receptor agonist (GLP1-RA) is recommended for greater efficacy, durability of treatment effect, and weight and hypoglycemia benefit. However, when treatment with GLP1-RA needs to be intensified, switch to insulin approach is still very common. It is also known that second generation basal insulins (2BI) provide similar or improved efficacy with a better safety profile compared to first generation basal insulins (1BI). Aim of this RESTORE-G sub-study was to perform a propensity-score adjusted comparative effectiveness analysis of adding-on/switching to 2BI vs. 1BI in patients on GLP1-RA therapy (±oral hypoglycemic agents) needing intensification. Table shows sample sizes, patients characteristics and effectiveness results.
Data shows that 2BI vs. 1BI was associated with significantly larger improvements in HbA1c and FBG both in add-on and switch approaches. In the switch approach, 2BI produced lower weight gain versus 1BI. Switching vs. adding on was associated with a more frequent use of short acting insulin. Both 1BI and 2BI were poorly titrated.

Disclosure
R.Napoli: Advisory Panel; Sanofi, Eli Lilly and Company, Novo Nordisk, Research Support; Novo Nordisk, AstraZeneca, Speaker's Bureau; Sanofi, Eli Lilly and Company, Novo Nordisk, AstraZeneca, MSD Life Science Foundation. M.Larosa: None. A.Nicolucci: Board Member; AstraZeneca, Research Support; Novo Nordisk, Sanofi, Sobi, Shionogi & Co., Ltd., AlfaSigma, Speaker's Bureau; Boehringer Ingelheim and Eli Lilly Alliance. M.Rossi: Research Support; Sanofi, Novo Nordisk, Shionogi & Co., Ltd., AlfaSigma. R.Candido: None. Restore-g study group: n/a.

Funding
Sanofi
781-P: Sustained-Release Formulation Development and Preclinical Evaluations of Monthly or Bimonthly Injectable Semaglutide and Tirzepatide
Authors: G JUNG JIN , CHANG SEUNG-GU 
Published: June 2023

Objective: Accumulated real-world data indicates strong tendencies to develop long-acting formulating drug. This study aimed for optimization and preclinical development of the sustained-release formulation of Semaglutide (PT403) and Tirzepatide (PT404) to explore whether they are applicable for bi-monthly (once every two months) injectable drugs.
Methods: Semaglutide or Tirzepatide dissolved in acetic acid with diverse combination of biodegradable PLGA polymers was applied to the ultrasonic spray dryer that produces API-encapsulated microspheres. The pharmacokinetic profiles of PT403 and PT404 were tested in rats and minipigs after a single subcutaneous injection.
Results: Both optimized formulation of PT403 and PT404 have demonstrated favorable physicochemical properties, showing uniformly sized microspheres (20±3 μm). Furthermore, the aggregation issue of Semaglutide, which was not observed in PT404, was solved by applying PROW technology. Also, increased encapsulation rates and higher drug loading (~8%) showed higher bioavailability, no initial burst and a short lag phase (&lt;3 days). Additionally, the release of PT403 initiated from 3 days to 70 days in minipigs, which potentially indicates every two months injectable (Q8W) in humans, compared to the once-a-weekly (QW) Semaglutide and Tirzepatide. Lastly, double injection of PT403 can easily reached the therapeutic window with 1.4 of the Peak-to-Through ratio, based on simulated PK profiles in repeated injection in human.
Conclusion: Evidence from recent formulation studies of PT403 and PT404 indicates that Peptron's SmartDepot technology is strongly applicable for long-acting drugs. The comprehensive results of formulation development, preclinical data, and mass production will provide the basis for successful clinical development of PT403 and PT404 as monthly or bi-monthly injectable diabetes and obesity drugs.

Disclosure
J.Jung: None. S.Chang: None.
79-LB: An Open-Label, Active-Controlled Phase 2 Evaluation of Novel GLP-1 Analog Ecnoglutide in Adults with Obesity
Authors: ZHU ZHIYI , LI YAO , ZHENG QING , ADEGBITE ERIC , ROSS STEPHEN , TELUSCA LIBNIR , JONES CATHERINE L. , FENAUX MARTIJN , XU SUSAN , JUNAIDI MOHAMMED K. 
Published: June 2023

Ecnoglutide (XW003) is a novel, long-acting GLP-1 analog being developed for the treatment of type 2 diabetes mellitus (T2DM) and obesity. We conducted a multi-center, open-label, active-controlled Phase 2b study in adults with a body mass index (BMI) ≥30 to ≤40 kg/m2. The trial was conducted at nine sites in Australia and New Zealand, with 206 participants enrolled. Participants were randomized to receive target doses of ecnoglutide at 1.2, 1.8, or 2.4 mg as once weekly SC injections or liraglutide (Saxenda®) at 3.0 mg as once daily injections for 26 weeks. Doses were increased by titration for up to 14 weeks before reaching the target dose. Safety and tolerability were assessed, along with efficacy parameters including change in body weight. At baseline, participants had a mean body weight of 100.67 ± 13.54 kg and BMI of 35.29 ± 2.76 kg/m2. After 26 weeks of dosing, participants receiving 1.2, 1.8, or 2.4 mg ecnoglutide weekly achieved a least square mean (LSM) body weight reduction from baseline of -11.5%, -11.2%, and -14.7%, respectively, compared to -8.8% for those receiving 3.0 mg liraglutide daily injections. Participants receiving 2.4 mg ecnoglutide showed significantly more pronounced body weight reduction compared to liraglutide (LSM difference -5.9, 95% confidence interval -10.4, -1.5; p&lt;0.001). Overall, treatment with ecnoglutide was safe and well tolerated. Treatment emergent AEs were reported in 93.5% of participants in the ecnoglutide groups and 98.0% in the liraglutide group. Gastrointestinal disorders were reported in 81.9% of ecnoglutide-treated participants and 80.4% of those receiving liraglutide, most of which were mild to moderate and most occurred during the dose escalation period. Two SAEs related to the study drug were reported. Both were cases of acute cholecystitis, one in a participant receiving 1.2 mg ecnoglutide and one in the liraglutide group.

Disclosure
Z. Zhu: Employee; Sciwind Biosciences. M. K. Junaidi: None. Y. Li: Employee; Sciwind Biosciences. Q. Zheng: Employee; Sciwind Biosciences. E. Adegbite: Employee; Sciwind Biosciences. S. Ross: None. L. Telusca: None. C. L. Jones: Employee; Sciwind Biosciences. M. Fenaux: Employee; Sciwind Biosciences, Stock/Shareholder; Terns Pharmaceuticals. S. Xu: Employee; Sciwind.

Funding
Sciwind Biosciences Co., Ltd.
797-P: Safety Profile of Once-Weekly Subcutaneous Semaglutide in a Real-World Adult Population with T2D
Authors: YALE JEAN-FRANÇOIS , MAJOR-PEDERSEN ATHELINE , CATARIG ANDREI-MIRCEA , JAIN RASHMI , MENZEN MARKUS , HOLMES PATRICK 
Published: June 2023

Real-world (RW) drug safety studies complement safety information from randomized clinical trials. This post hoc analysis of pooled data from nine global non-interventional studies (SURE program: 10 countries, ~30 weeks duration) investigated the safety and prescription patterns of once-weekly (OW) semaglutide in 3,505 adults with T2D in routine practice, overall and by patient subgroup and medical specialty stratification. All safety data reported by site physicians were collected and presented using descriptive statistics. Results: Tables 1 and 2. A two-fold increase in level-2 hypoglycemia was associated with insulin use and microvasculopathy. No new safety concerns were observed with OW semaglutide in this large, diverse, RW population with T2D; the safety profile was in line with that of phase 3 trials of semaglutide.

Disclosure
J.Yale: Advisory Panel; Sanofi, Novo Nordisk Canada Inc., Eli Lilly and Company, Bayer Inc., Boehringer Ingelheim (Canada) Ltd., Abbott, Mylan, Research Support; Sanofi, Novo Nordisk Canada Inc., Bayer Inc., Speaker's Bureau; Sanofi, Novo Nordisk Canada Inc., Eli Lilly and Company, Bayer Inc., AstraZeneca, Merck & Co., Inc., Boehringer Ingelheim (Canada) Ltd., Janssen Pharmaceuticals, Inc., Abbott, Dexcom, Inc. A.Major-pedersen: Employee; Novo Nordisk A/S. A.Catarig: Employee; Novo Nordisk, Stock/Shareholder; Novo Nordisk. R.Jain: Employee; Novo Nordisk Global Business Services, Stock/Shareholder; Novo Nordisk Global Business Services. M.Menzen: Advisory Panel; Boehringer Ingelheim Pharma GmbH&Co.KG, Novo Nordisk A/S, Ascensia Diabetes Care, Eli Lilly and Company, Novartis, Speaker's Bureau; Abbott Diabetes, AstraZeneca, Santis, Boehringer Ingelheim Pharma GmbH&Co.KG, Novo Nordisk A/S, Bayer Inc., Eli Lilly and Company, Novartis. P.Holmes: Advisory Panel; Boehringer-Ingelheim, Sanofi, Research Support; Novo Nordisk, Roche Diagnostics, Speaker's Bureau; Novo Nordisk, AstraZeneca, Eli Lilly and Company, Bayer Inc.

Funding
Novo Nordisk A/S
802-P: Beneficial Effects of a Functionally Selective Insulin on Vascular Function and Liver Triglycerides
Authors: OLSEN GRITH S. , PEDERSEN THOMAS A. , SLAABY RITA , HANSEN BO F. , GLENDORF TINE , DEMOZAY DAMIEN , HVID HENNING , NISHIMURA ERICA , BRANDT JAKOB , POVLEN GRO 
Published: June 2023

Selective insulin resistance, where insulin's ability to lower blood glucose via the Akt signaling pathway gradually decreases while retaining its effectiveness in activating other signaling pathways (e.g. MAPK), is a key pathophysiological mechanism underlying the hyperglycemia, dyslipidemia and vascular dysfunction in type 2 diabetes (T2D). Here we hypothesize that a selective signaling insulin analog that activates Akt signaling but has a considerably reduced effect on MAPK should counteract selective insulin resistance and provide effective glucose lowering with improved vascular function, reduced hepatic lipid accumulation and generally alleviate insulin resistance over time compared to human insulin (HI). NNC-965, a basal insulin analog with 4 amino acid modifications and a C18 fatty diacid, was designed as a functionally selective insulin, with greater Akt than MAPK activation in several cellular systems and in vivo. NNC-965 fully activates glucose regulating pathways, including inhibition of glucose output, glycogen accumulation and inhibition of gluconeogenic mRNAs in rat hepatocytes as well as stimulation of glucose uptake and inhibition of lipolysis in rat adipocytes. In contrast, NNC-965 displayed reduced induction of lipogenic mRNA and de novo lipogenesis in rat liver cells compared to HI. In a mouse model of T2D, treatment with NNC-965 for 6 weeks to the same glucose level as insulin 700 (an insulin degludec-like analog) resulted in 35% less liver triglycerides and improved acetylcholine mediated vasodilation in ex vivo studies using mesenteric arterioles. In conclusion, NNC-965 is a novel functionally selective insulin analog that can potentially improve insulin resistance and eventually reduce cardiovascular risk by restoring balanced insulin signaling.

Disclosure
G.S.Olsen: Employee; Novo Nordisk A/S. G.Povlen: Employee; Novo Nordisk. T.A.Pedersen: Employee; Novo Nordisk A/S. R.Slaaby: Employee; Novo Nordisk, Stock/Shareholder; Novo Nordisk. B.F.Hansen: Employee; Novo Nordisk A/S, Stock/Shareholder; Novo Nordisk A/S. T.Glendorf: Employee; Novo Nordisk A/S, Stock/Shareholder; Novo Nordisk A/S. D.Demozay: None. H.Hvid: Employee; Novo Nordisk A/S. E.Nishimura: Employee; Novo Nordisk A/S. J.Brandt: Employee; Novo Nordisk A/S.