bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hypoglycemia Unawareness in T1DM Is Associated with Altered Brain Default Mode Network Connectivity
Authors: GROSKREUTZ DEREK , HWANG JANICE , SEO DONGJU , LACADIE CHERYL , PARIKH LISA , BELFORT-DEAGUIAR RENATA , SCHEINOST DUSTIN , SINHA RAJITA , CONSTABLE TODD , SHERWIN ROBERT 
Published: June 2018

The impact of hypoglycemia awareness (HA) on brain resting state connectivity remains unclear. To examine the impact of HA on the default mode network (DMN), a functional network in the brain that is active during wakeful rest and associated with introspection, 12 T1DM individuals with hypo unawareness (T1DM-UW) (by Clarke score) (7F/5M, age 44±12 years, BMI 26.4±4.2 kg/m2, HbA1c 7.1±0.7) and 15 T1DM-Aware (AW) (10F/5M, age 30±7, BMI 24.5±3.1, HbA1C 7.1±0.9) individuals underwent resting state BOLD fMRI scanning to assess the DMN during a two-step euglycemic (Eu)-hypoglycemic (Hypo) clamp (90-60 mg/dl). T1DM-AW individuals exhibited a hypoglycemia-induced decrease in DMN connectivity (P&lt;0.001). In contrast, T1DM-UW individuals showed no difference in connectivity between conditions. Moreover, the degree of DMN inhibition correlated inversely with plasma cortisol (r=-0.432, p=0.031), norepinephrine (r=-0.40, p=0.038) and positively with hypoglycemia symptom scores (r=0.40, p=0.037). These findings suggest that, unlike T1DM-AW individuals, hypoglycemia fails to elicit changes in the DMN amongst T1DM-UA individuals. Furthermore, the change in DMN connectivity is associated with measures of physiological and interoceptive responses to stress. These findings highlight the need for future studies to investigate whether avoidance of hypoglycemia can restore brain connectivity patterns.

Disclosure
D. Groskreutz: None. J. Hwang: None. D. Seo: None. C. Lacadie: None. L. Parikh: None. R. Belfort-DeAguiar: Research Support; Self; GlaxoSmithKline plc.. D. Scheinost: None. R. Sinha: None. T. Constable: None. R. Sherwin: Other Relationship; Self; QuintilesIMS, MannKind Corporation. Research Support; Self; Regeneron Pharmaceuticals, Inc.. Other Relationship; Self; ICON plc..
Dulaglutide Has Favorable Outcomes in Elderly or Renal Impairment Patients with Type 2 Diabetes
Authors: KANEKO SHIZUKA , UEDA YOUHEI , TAHARA YUMIKO 
Published: June 2018

In Japan, society is aging. Additionally, dialysis is performed in one out of 400 people. Safe, effective and convenient therapies for elderly or renal impairment type 2 diabetic patients (T2D) including those undergoing dialysis are needed. We investigated the the long-term efficacy and safety of a new once weekly GLP-1RAg dulaglutide (Dura) on glycemic control in those. We conducted two different retrospective analyses of 2 year efficacy and safety of Dura in T2D according to; 1)subgroups stratified by ages (≤70 years old or &gt;71 years old), 2) renal impairment including those undergoing dialysis. Regarding 1) Of 322 T2D, 214 elderly T2D (109 males, 76.6±6.9 years old, disease duration of 7.6±7.4 years, HbA1c 8.3±1.8%, BMI 24.1±4.1) and 1younger T2D (48 males, 58.4±10.6 years old, disease duration of 5.6±5.6 years, HbA1c 7.9±1.4%, BMI 25.5±4.4) were newly administered Dura weekly. Elderly and younger T2D treated with Dura achieved 7.0±6.9% and 7.2±6.9% in HbA1c after 2 years respectively. 20 elderly T2D were injected under help with care persons due to cognitive impairment. One patient discontinued Dura due to intolerance. Nocturnal hypoglycemia never occurred. 2) 33 patients with renal impairment (69.5±10.2 years old, HbA1c 7.6±1.0%, eGFR 42.3±7.9 mL/min/1.73m2) including 6 patients undergoing dialysis (5 hemodialysis and 1 peritoneal dialysis). The levels of eGFR remained those at the start of Dura therapy. Only one patient with hemodialysis discontinued Dura due to vomiting. Weekly GLP-1RAg provides more effective and safer glycemic control in elderly T2D with/without renal impairment including dialysis. It might be expected to reduce: patient burden due to weekly injections, risk of hypoglycemia, burden on care givers in an aging society. It might also be expected to improve QoL of patients due to a reduced burden when taking medicines daily or hypoglycemia, and due to saving care person’s burden in elderly society which is workforce shortage, result in reduce of medical costs.

Disclosure
S. Kaneko: Advisory Panel; Self; Novo Nordisk A/S. Speaker's Bureau; Self; Novo Nordisk A/S, Eli Lilly and Company, Mitsubishi Tanabe Pharma Corporation, Novartis Pharma K.K., Sanwa Kagaku Kenkyusho Co., Ltd.. Other Relationship; Self; Elsevier. Speaker's Bureau; Self; Kowa Pharmaceuticals America, Inc., Ono Pharmaceutical Co., Ltd., Astellas Pharma US, Inc., Sanofi, Nippon Boehringer Ingelheim Co. Ltd., AstraZeneca, Sumitomo Dainippon Pharma Co., Ltd.. Speaker's Bureau; Spouse/Partner; Sumitomo Dainippon Pharma Co., Ltd., Kyowa Hakko Kirin Co., Ltd., Otsuka Holdings Co., Ltd., Mitsubishi Tanabe Pharma Corporation, Biogen, Eisai Co., Ltd., Bayer AG, Novartis Pharma K.K., Ono Pharmaceutical Co., Ltd., Nihon Pharmaceutical Co., Ltd., Fujimoto Pharmaceutical Corporation. Y. Ueda: None. Y. Tahara: None.
Exploring Two Dose Regimens of ITCA 650 to Switch from Stable Liraglutide Therapy in Type 2 Diabetes (T2D)
Authors: RASOULI NEDA , ROSENSTOCK JULIO , NAKHLE SAMER , SCHWARTZ BRIAN , PRABHAKAR PRAKASH , KRUGER SYDNEY L. , HUANG HOLLY , BARON MICHELLE A. 
Published: June 2018

ITCA 650 is an investigational titanium osmotic mini pump that is subdermally placed in the abdominal wall during a brief office procedure to continuously deliver exenatide over 3 and 6-month periods and has the potential to improve medication adherence because patients do not self-administer. In this 26 week, open-label phase 3b study, 136 patients with T2D receiving liraglutide (1.2 to 1.8 mg/d) and metformin (≥1000 mg/d) were randomized to either the standard ITCA 650 dose regimen used in phase 3 trials of 20 mcg/d for 13 weeks followed by a 60 mcg/d maintenance dose (for 13 weeks in this study) or starting directly with the maintenance dose of 60 mcg/d for 26 weeks. The last injection of liraglutide occurred 2 days prior to randomization. The primary endpoint compared the incidence of nausea (N) and vomiting (V) between the two dose regimens. Switching from liraglutide to either dose regimen of ITCA 650 had a similar incidence of transient mild to moderate N/V (Table). Of note, 3 sites, which recruited 25% of the study population, accounted for 47% and 68% of the total N/V seen in the study. 4 patients discontinued due to GI AEs. Glycemic control remained stable in both groups. At Week 26, significant weight reduction was observed in both groups (p&lt;0.vs. baseline).
In conclusion, patients on stable liraglutide therapy can be switched to ITCA 650 60 mcg/d without the need for up-titration from a lower dose.

Disclosure
N. Rasouli: Consultant; Self; AstraZeneca, Intarcia Therapeutics, Inc. 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.. S. Nakhle: None. B. Schwartz: Employee; Self; Intarcia Therapeutics, Inc.. P. Prabhakar: None. S.L. Kruger: None. H. Huang: None. M.A. Baron: Employee; Self; Intarcia Therapeutics, Inc..
Efficacy and Safety of Glucagon-Like Peptide-1 Receptor Agonist (GLP-1RA) plus Basal Insulin vs. GLP-1RA in Type 2 Diabetes Mellitus—A Systematic Review and Meta-analysis
Authors: SATTI MUNIZA M. , O'BRIEN TIMOTHY , LIEW AARON 
Published: June 2018

Combination therapy with Glucagon-like peptide-1 receptor agonist (GLP-1RA) and basal insulin represents a new therapeutic option for diabetes mellitus. We hypothesized that GLP-1RA plus basal insulin is more efficacious, safer and tolerable than GLP-1RA for patients with type 2 diabetes mellitus (T2DM). Randomized controlled trials (RCTs) comparing GLP-1RA plus basal insulin vs. GLP-1RA were searched using PubMed, Cochrane library and www.ClinicalTrials.gov database. Inclusion criteria were: (1) RCTs; (2) comparison between GLP-1RA plus basal insulin vs. GLP-1RA; (3) duration of treatment between 24-30 weeks; and (4) T2DM. Four RCTs with 2,732 participants were included in this meta-analysis. Compared with GLP-1RA alone, GLP-1RA plus basal insulin was associated with a significant reduction in HbA1c (Mean difference [MD]: -0.79%; 95% CI [confidence interval]: -0.96,-0.61; P&lt;0.001) and fasting plasma glucose (FPG) (MD: -2.03mmol/l; 95% CI: -2.28, -1.77; p&lt;0.001). More participants achieved HbA1c ≤7% in the GLP-1RA plus basal insulin group (Odds ratio [OR]: 4.66; 95% CI: 3.00, 7.23; p&lt;0.001). GLP-1RA plus basal insulin was associated with more symptomatic hypoglycaemia (OR: 7.04; 95% CI: 3.81, 13.00; p&lt;0.001) and weight gain (MD: 2.46kg; 95% CI: 2.08, 2.84; P&lt;0.001). There was no significant difference in treatment emergent adverse effects (OR: 0.80; 95% CI: 0.57, 1.11; p=0.18) and discontinuation due to adverse events (OR: 0.52; 95% CI: 0.26, 1.03; p=0.06) between both groups. GLP-1RA plus basal insulin is more efficacious for HbA1c and FPG reduction when compared with GLP-1RA in patients with T2DM. Symptomatic hypoglycaemia and weight gain were more common with GLP-1RA plus basal insulin, but discontinuation due to adverse events was similar between both groups.

Disclosure
M.M. Satti: None. T. O'Brien: Advisory Panel; Self; Merck Sharp & Dohme Corp., Novo Nordisk A/S. Speaker's Bureau; Self; AstraZeneca. A. Liew: Advisory Panel; Self; Eli Lilly and Company, Novo Nordisk A/S.
Cholesterol 7 Alpha–Hydroxylase (CYP7A1) Activity and 7–Alpha–Hydroxy–4–Cholesten–3–One (C4) Are Not Translatable Biomarkers of Glucagon Receptor (GCGR) Activation
Authors: CAMACHO RAUL , LI WENYU , KIRCHNER THOMAS , ZHANG RUI , BONILLA FANY , JIAN WENYING , GAO BIN , SINHAROY RANABIR , LEONARD JAMES , CONNOLLY THOMAS 
Published: June 2018

Glucagon-like peptide 1 receptor/glucagon receptor (GLP–1R/GCGR) dual agonists are being pursued for obesity and type 2 diabetes mellitus (T2DM). A biomarker for GCGR would aid in optimizing receptor balance and in modeling dose selection to avoid potential adverse events from excess GCGR agonism. It has been reported that glucagon treatment decreases CYP7A1 transcription in primary rat and human hepatocytes, whereas GCGR antagonists increase CYP7A1 mRNA in mice and its product, 7–HCO (the precursor of C4), in diabetic patients. We tested glucagon, insulin, dulaglutide, and a GLP–1R/GCGR dual agonist, Cpd. A, in primary human and cynomolgus monkey hepatocytes. All treatments decreased CYP7A1 expression in monkey hepatocytes. C4 was undetectable in the culture media. Lean mice or rats treated with Cpd. A showed no changes in non–fasting C4. Diet–induced obese mice treated with Cpd. A or a GCGR–null analog had decreased non–fasting C4. To test whether GCGR (and/or GLP–1R) agonism affects plasma C4 in higher species, we infused saline or glucagon (at two different rates) on a background of somatostatin infusion in cynomolgus monkeys dosed with dulaglutide the day before. C4 levels did not differ between treatment groups. To determine whether this lack of an effect was specific to pre-clinical species, T2DM patients were dosed once a week for 4 weeks with a placebo or 2 doses of a second GLP-1R/GCGR dual agonist. There were no statistically significant differences in C4 levels between groups. Hence, in contrast to GCGR antagonists, GCGR and/or GLP–1R agonists did not modulate C4 levels in pre–clinical species or in T2DM patients.

Disclosure
R. Camacho: Employee; Self; Janssen Research & Development. W. Li: None. T. Kirchner: None. R. Zhang: Employee; Self; Janssen Research & Development. F. Bonilla: None. W. Jian: None. B. Gao: None. R. SinhaRoy: Employee; Self; Janssen Research & Development. Employee; Spouse/Partner; Bristol–Myers Squibb Company. Stock/'Shareholder; Self; Merck & Co., Inc.. Stock/Shareholder; Spouse/Partner; Merck & Co., Inc. J. Leonard: Employee; Self; Janssen Research & Development. T. Connolly: None.
FTY720 Treatment Rejuvenates ß-Cell Function and Improves Cardiac Function in Diabetic Nonhuman Primates (NHPs)
Authors: WANG YIXIN , LIU YONGQIANG , WEI QIAO , WANG XIAOLI , SUN GAO , XIAO YONG-FU , YU GUOLIANG , MA ZHONGMIN A. 
Published: June 2018

Pancreatic β-cell regeneration is considered as a possible therapy for cure of type 2 diabetes (T2D). It has been reported that administration of FTY720, a sphingosine 1-phosphate (S1P) receptor modulator, to db/db mice led to sustained normalization of hyperglycemia by stimulating β-cell in vivo regeneration through PI3K-dependent regulation of cyclin D3 and p57KIP2. To further evaluate the therapeutic potential of FTY720 in the treatment of T2D, we examined the effects of FTY720 on glucose homeostasis in spontaneous diabetic NHP model. NHPs with mean fasting glucose (FG) level of 249 mg/dL were randomly divided into the control (vehicle) and the FTY720-treatment group. FTY720 was orally administered at 5 mg/kg to diabetic NHPs once per day and the FG and HbA1c levels were measured biweekly. Here we show that FTY720 treatment of diabetic NHPs significantly lowered their FG and HbA1c in two weeks. After 10 weeks of treatment, their FG and HbA1c levels remained low and their glucose tolerance was significantly improved. To determine the effect of FTY720 on β-cell function, IVGTT was performed. Following glucose injection, the insulin levels in the control NHPs barely changed. In contrast, the FTY720-treated NHPs secreted large amount of insulin in response to glucose stimulation, consistent with β-cell in vivo regeneration observed in mice. We also evaluated the cardiac function in these NHPs by echocardiography, from which ejection fraction (EF) and fractional shortening (FS) are found abnormally lower in diabetic NHPs (EF=60% and FS=30%) than that in normal NHPs (EF=68% and FS=43%). After 10 weeks of treatment, however, EF in the treatment group was significantly increased from 60% to 70% and FS from 30% to 38% while these values remained abnormally low in the control group. Our data strongly suggest that FTY720 has a great therapeutic promise for the treatment of T2D with benefit to improve the cardiac function in the patients.

Disclosure
Y. Wang: None. Y. Liu: None. Q. Wei: Employee; Self; Crownbio.Inc.. X. Wang: None. G. Sun: None. Y. Xiao: None. G. Yu: None. Z.A. Ma: None.
A Phase 3 Study to Assess the Efficacy and Safety of Ipragliflozin in Russian Patients with Type 2 Diabetes Mellitus Inadequately Controlled by Metformin
Authors: SHESTAKOVA MARINA V. , WILDING JOHN P. , WILPSHAAR WIM , TRETTER REINER N. , ORLOVA VALERIA L. , VERBOVOY ANDREY F. 
Published: June 2018

Aim: To assess the efficacy and safety of ipragliflozin as add-on therapy to metformin in Russian patients with T2DM.
Methods: In this double-blind trial conducted in 14 centers in Russia, 165 patients were randomized 2:1 to ipragliflozin (50 mg/day) or placebo for 24 weeks while continuing metformin. Patients who had HbA1c ≥7.0% at Week 12 received open-label ipragliflozin (50 mg/day) in addition to the blinded drug from Week 12-24.
Results: Significant reductions in HbA1c and body weight from baseline to Week 12 in favor of ipragliflozin were observed; the incidence of AEs was similar in both groups (Table). HbA1c and weight improvements were sustained from Week 12-24 in patients who remained on 50 mg ipragliflozin (mean change from Week 12: 0.16% and -0.48 kg, respectively; p&gt;0.05). Uptitration to 100 mg ipragliflozin led to a further reduction in body weight (mean change from Week 12: -0.65 kg, P=0.004) and an additional 13% (9/69) achieving HbA1c &lt;7% at Week 24. Incidence of AEs was similar in 50 mg (23.7%) and 100 mg groups (24.6%). No clinically significant changes in vital signs were noted during the study.
Conclusion: 50 mg Ipragliflozin added to metformin significantly reduced HbA1c and body weight after 12 weeks and showed a comparable safety profile as placebo. Uptitration to 100 mg/day conferred added benefits with no additional safety concerns.
Table. Efficacy and AE results from baseline to Week 12 Baseline Iprag/PlaceboEOT Week 12 Iprag/PlaceboChange Iprag/Placebo*Adjusted mean difference to placebo (95% CI)*P valueEfficacy endpoints (FAS)HbA1c, %8.40 (0.94)/8.46 (0.96)7.38 (0.90)/7.69 (1.11)-1.01 (0.85)/-0.77 (1.10)-0.26 (-0.53, 0.00)0.048Body weight, kg92.88 (16.25)/89.54 (15.60)90.87 (16.42)/88.92 (14.89)-2.01 (2.47)/-0.62 (2.14)-1.34 (-2.06, -0.61)&lt;0.001Safety endpoints (SAF)AEs, n (%)-32 (29.1)/19 (34.5)- - -Drug-related AEs, n (%)-12 (10.9)/4 (7.3)- - -*ANCOVA model with treatment as fixed effect, center as random effect, and baseline value as covariate. Data are presented as mean (SD) unless stated otherwise. Ipragliflozin (FAS = 109; SAF = 110) and placebo (FAS or SAF = 55). AEs, adverse events; EOT, end of treatment; FAS, full analysis set; Iprag, ipragliflozin; SAF, safety analysis set.

Disclosure
M.V. Shestakova: None. J.P. Wilding: Other Relationship; Self; Astellas, AstraZeneca, Boehringer Ingelheim GmbH, Janssen Pharmaceuticals, Inc., Novo Nordisk Inc., Sanofi, Eli Lilly and Company, Orexigen Therapeutics, Inc., Merck & Co., Inc. W. Wilpshaar: Employee; Self; Astellas. R.N. Tretter: Employee; Self; Astellas Pharma Europe B.V.. V.L. Orlova: None. A.F. Verbovoy: None.
Oral Semaglutide Does Not Affect the Bioavailability of the Combined Oral Contraceptive Ethinylestradiol/Levonorgestrel
Authors: JORDY ANDREAS BÔRSTING , BREITSCHAFT ASTRID , CHRISTIANSEN ERIK , GRANHALL CHARLOTTE , HANSEN CILIE W. , HOUSHMAND-OREGAARD AZADEH , BAEKDAL TINE A. 
Published: June 2018

Semaglutide is a glucagon-like peptide (GLP-1) analog co-formulated with the absorption enhancer, sodium N-(8-[2-hydroxybenzoyl] amino) caprylate (SNAC), to allow oral administration. The effect of oral semaglutide on the pharmacokinetics (PK) of the combined oral contraceptive (OC) ethinylestradiol (EE; 0.03 mg)/levonorgestrel (LN; 0.15 mg) was assessed in an open-label, one sequence crossover trial. Healthy post-menopausal females (n=25) received 8 days of OC alone and 8 days of OC with oral semaglutide (dose escalated to steady state at week 6: 1 week at 3 mg dose, 1 week at 7 mg dose, 4 weeks at 14 mg dose). Primary endpoints were the areas under the plasma concentration−time curve for EE and LN during a dosing interval (0−24 h) at steady state (AUC0−24h,SS). Secondary endpoints included other PK parameters, safety and tolerability. Total exposure of EE and LN were similar for OC alone vs. OC with oral semaglutide, and oral semaglutide did not affect the maximum plasma exposure (Cmax,SS) of EE or LN. AUC0−24h,SS and Cmax,SS ratios for EE and LN were within the predefined no effect interval (0.8−1.25) (Figure). Adverse events with oral semaglutide were consistent with previous trials and expected GLP-1 receptor agonist class effects. These data indicate that oral semaglutide did not affect the bioavailability of the combined OC.

Disclosure
A. Bôrsting Jordy: Employee; Self; Novo Nordisk A/S. A. Breitschaft: None. E. Christiansen: Stock/Shareholder; Self; Novo Nordisk A/S. Employee; Self; Novo Nordisk A/S. C. Granhall: Employee; Self; Novo Nordisk A/S. C.W. Hansen: Employee; Self; Novo Nordisk A/S. A. Houshmand-Oregaard: Employee; Self; Novo Nordisk A/S. T.A. Baekdal: Stock/Shareholder; Self; Novo Nordisk A/S. Employee; Self; Novo Nordisk A/S.
Duodenal Mucosal Resurfacing Elicits Improvement in Glycemic and Hepatic Parameters in Type 2 Diabetes—One-Year Multicenter Study Results
Authors: VAN BAAR ANNIEKE C.G. , NIEUWDORP MAX , HOLLEMAN FRITS , DEVIERE JACQUES , CRENIER LAURENT , HAIDRY REHAN , BATTERHAM RACHEL L. , HOPKINS DAVID , GRUNERT LEONARDO RODRIGUEZ , NETO MANOEL GALVAO , VIGNOLO PAULINA , COSTAMAGNA GUIDO , BERGMAN JACQUES J. 
Published: June 2018

Aims: Duodenal Mucosal Resurfacing (DMR) is a novel endoscopic procedure which has been shown to improve glycemic control at 6 months in type 2 diabetes (T2D). It is thought to exert insulin-sensitizing effects. DMR entails catheter based circumferential mucosal lifting followed by hydrothermal ablation. This study aimed to extend DMR experience, determining efficacy over 12 months in T2D patients on stable oral glucose lowering treatment.
Methods: Single arm, multicenter study. 46 T2D patients on oral glucose lowering medication received a DMR procedure. Impact on glycemic control (HbA1c and fasting plasma glucose), insulin resistance (HOMA-IR) and liver enzymes (AST and ALT) was determined at baseline and 1, 3, 6, 9, 12 mo post DMR. Glucose lowering medication was kept stable 6 mo post DMR and adjusted according to local guidelines thereafter.
Results: See figure 1. At 12 mo: δHbA1c -1.0±0.2% (p ≤ 0.001), δFPG -41±8 mg/dL (p ≤ 0.001), δHOMA-IR -3.6±0.9 (p = 0.005), δ weight -2.7±0.6kg (p = 0.003), δALT -10±2 (p = 0.005) and δAST -6±2 (p=0.002). DMR was well tolerated with no related serious adverse events or unexpected adverse device events reported.
Conclusions: Single DMR treatment elicited significant and clinically relevant reductions in glycemic and hepatic parameters that were sustained at 12 months, suggesting considerable potential of DMR for the treatment of T2D.

Disclosure
A.C.G. van Baar: None. M. Nieuwdorp: None. F. Holleman: Other Relationship; Self; Sanofi-Aventis, Bioton, AstraZeneca. J. Deviere: None. L. Crenier: None. R. Haidry: None. R.L. Batterham: Research Support; Self; Fractyl Laboratories, Inc.. Board Member; Self; Novo Nordisk Inc.. Consultant; Self; Novo Nordisk Inc.. Advisory Panel; Self; National Institute for Health and Clinical Excellence, Nestlé. Speaker's Bureau; Self; Orexigen Therapeutics, Inc., Medtronic. D. Hopkins: Advisory Panel; Self; Novo Nordisk A/S, Sanofi-Aventis, Roche Pharma. Speaker's Bureau; Self; Janssen Pharmaceuticals, Inc., AstraZeneca, Eli Lilly and Company, Napp Pharmaceuticals, Ltd., Sunovion Pharmaceuticals Inc.. Other Relationship; Self; Diabetes UK. Speaker's Bureau; Self; Fractyl Laboratories, Inc.. L. Rodriguez Grunert: None. M. Galvao Neto: Consultant; Self; Fractyl Laboratories, Inc., GI Dynamics Inc., GI Windows, Inc., Ethicon US, LLC., Apollo EndoSurgery. P. Vignolo: None. G. Costamagna: None. J.J. Bergman: Research Support; Self; Fractyl Laboratories, Inc..