bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of Combination Therapy with Liraglutide plus Canagliflozin on HGP and HbA1c vs. Each Therapy Alone in T2DM
Authors: ABDUL-GHANI MUHAMMAD , ALI ALI M. , MARTINEZ ROBERT A. , ADAMS JOHN M. , CERSOSIMO EUGENIO , TRIPLITT CURTIS L. , DEFRONZO RALPH A. 
Published: June 2018

Background: We previously have shown that SGLT2 inhibitors cause an increase in HGP accompanied with an increase in plasma glucagon concentration. We hypothesized that the increase in plasma glucagon concentration is, at least in part, responsible for the increase in HGP. The aim of the present study was to examine whether inhibition of glucagon secretion by liraglutide can prevent the increase in HGP.
Research Design and Methods: 51 T2DM patients (age=51±1 yr; 40% female; BMI=34.6±0.7; diabetes duration=6.8±0.8 yr; FPG=175±7; HbA1c=8.3±0.1%) were randomized to receive for 16 weeks: (i) canagliflozin 300 mg; (ii) liraglutide 1.8 mg; or (iii) canagliflozin 300 mg plus liraglutide 1.8 mg. HGP (measured with 3-3H-glucose infusion) and plasma glucagon concentration were measured before and after 16 weeks of treatment.
Results: Canagliflozin monotherapy caused a significant reduction in HbA1c (-1.1±0.2%, p&lt;0.01) accompanied with an increase in plasma glucagon concentration (by 28%, p&lt;0.05) and HGP (by 15%, p&lt;0.05) which lasted for 16 weeks. Conversely, liraglutide monotherapy caused a 1.6±0.5% (p&lt;0.01) reduction in HbA1c accompanied by a small (6%) reduction in HGP (P=NS) without significant change in fasting plasma glucagon concentration. The combination of canagliflozin plus liraglutide caused a greater reduction in HbA1c (1.9±0.5%, p&lt;0.vs. canagliflozin and p=NS vs. liraglutide) and attenuated the increase in fasting plasma glucagon and basal HGP at 16 weeks.
Conclusion: These results: (1) support a possible role for increased plasma glucagon levels in the long term maintenance of increase in HGP caused by SGLT2i, and (2) suggest that factors other than/in addition to glucagon contribute to the initiation of the increase in HGP.

Disclosure
M. Abdul-Ghani: None. A.M. Ali: None. R.A. Martinez: None. J.M. Adams: None. E. Cersosimo: Research Support; Self; AstraZeneca, VeroScience, LLC.. Speaker's Bureau; Self; AstraZeneca, Sanofi, Janssen Pharmaceuticals, Inc., Eli Lilly and Company. C.L. Triplitt: Speaker's Bureau; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Janssen Pharmaceuticals, Inc., Eli Lilly and Company. Consultant; Self; Sanofi, Novo Nordisk Inc. R.A. DeFronzo: Speaker's Bureau; Self; AstraZeneca, Novo Nordisk Inc.. Advisory Panel; Self; AstraZeneca, Novo Nordisk Inc., Janssen Pharmaceuticals, Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Elcelyx Therapeutics, Inc., Intarcia Therapeutics, Inc.. Research Support; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Janssen Pharmaceuticals, Inc., Takeda Pharmaceuticals U.S.A., Inc..
Qualitative and Quantitative Effect of IDegLira Compared with the Nonfixed Administration of Degludec and Liraglutide
Authors: KOUTSOVASILIS ANASTASIOS , SOTIROPOULOS ALEXIOS , PAPADAKI DESPINA , BLETSA EVDOXIA , KOKOTOS GEORGIOS , KOUNELAKIS IOANNIS , BOUSBOULAS STAVROS , PEPPAS THEODOROS 
Published: June 2018

Introduction: The efficacy and safety of IDegLira and the benefits of its complementary mode of action have been examined in the large global DUAL clinical trial program.
Aim: The aim of this study is to examine the qualitative and quantitative effect of IDegLira compared to the non-fixed adiministration of degludec and liraglutide.
Methods: Uncontrolled type 2 diabetes (T2D) patients (n=473) were included in the study. 158 patients on oral antidiabetic drugs (OADs) switched to OADs and IDegLira (Group A), 163 on OADs and liraglutide switched to degludec and the existing therapeutic regime (Group B) and 152 patients on degludec and OADs switched to liraglutide and the existing treatment (Group C). All patients also received metformin while none of them received sulfonylurea. Follow-up was 12 months and changes in HbA1c, cardiometabolic risk factors, and treatment adherence (with the 8-item Morisky Medication Adherence Scale) were recorded.
Results: There was no difference at baseline between the three Groups as to age (p=0.224), diabetes duration (p=0.322), HbA1c (8.56±1.12, p=0.116) and BMI (32.14±3.56, p=0.142). The mean HbA1c after 12 months was 6.79±0.77, 7.14±1.19, 7.18±1.07 (p=0.033) for Groups A, B and C respectively. More patients achieved the therapeutic target for HbA1c in Group A (p=0.048). The weight change was -3.2±1.2 Kg for Group A, 1.2±1.1 Kg for Group B and -4.3±1.7 Kg for Group C (p&lt;0.001). There was no difference in the hypoglycemic episodes between the three Groups (p=0.251). Greater adherence was achieved in Group A compared to Group B and C (7.58±1.08, 6.38±1.28 and 6.44±1.16, p=0.031). Total insulin dose was lower for Group A (p=0.040).
Conclusions: Uncontrolled patients on oral antidiabetic drugs when switched to a therapeutic regimen with IDegLira achieved a significant improvement in their glycemic control with a significant adherence to their therapeutic regimen while the adherence in a non-fixed combination was not significant enough.

Disclosure
A. Koutsovasilis: None. A. Sotiropoulos: None. D. Papadaki: None. E. Bletsa: None. G. Kokotos: None. I. Kounelakis: None. S. Bousboulas: None. T. Peppas: None.
Possibility of Liraglutide for Prevention of Dementia Progression in Patients with Type 2 Diabetes
Authors: YOSHIDA MAMI , MORIMOTO TAKAKO , OH ERIKO , YAMAMOTO NAOMUNE , NAGATA KOUJI , SAEKI AKIO , SASAKI EUN , YOSHIDA SHIGERU , KUZUYA TAKESHI , OHSAWA NAKAAI , SUGINO MASAKAZU 
Published: June 2018

Purpose: The aim of this study was to assess the efficacy of liraglutide on prevention of dementia in elderly patients with type 2 diabetes (T2DM).
Subjects and methods: We studied 34 (male 8/female 26) outpatients with 65 years or older, whose HbA1c was over 7.0% by other antidiabetic treatment. We administrated liraglutide 0.3mg before breakfast for the first week, 0.6mg for the second week, and 0.9mg after the third week. 34 subjects in the liraglutide group (G group) [8 males/ 26 females, 75.7±7.8 years old, HbA1c 7.5 ± 0.38%] were followed-up for 3 years. We examined Voxel-based Specific Regional Analysis System for Alzheimer’s Disease (VSRAD) on MRI, max-IMT measured by carotid artery echo, visceral fat area, HbA1c, FPG, serum HDL/LDL level, and TG, both before and after the treatment.10 patients in the linagliptin group (D group) in which ages, HbA1c, visceral fat, and VSRAD were matched with G group were used as controls.
Result: After 3 years, VSRAD was not changed in G group and was significantly deteriorated in D group (G group: 1.22±0.73→1.19±0.73 (NS) vs. G group: 1.36±0.87→1.53±0.99 (p = 0.022)). Max IMT was significantly improved in G group (2.42±1.65→2.14±1.40 (p =0.035) vs. 2.25±1.19→2.19±1.01(NS)). Visceral fat was significantly reduced in G group (137.1±54.0→128.0±59.3 (p &lt;0.01) vs. 114.3±55.8 → 116.5±66.2 (NS)). HbA1c (7.5±0.38 → 6.8±0.46 vs. 7.3±0.55 → 6.9±0.42%), FPG (137±19 → 121±11 vs. 135 ±21 → 118±16 mg/dl), were significantly improved in both groups (p&lt;0.01). No hypoglycemia requiring medical intervention was observed. Lipid was significantly improved only in TG in G group (TG: 162±53→145±34 (p &lt;0.01) vs. 185±45→159±48 mg/dl (NS)). There was no onset of dementia.
Conclusion: Liraglutide improved the glycemic control, lipid profile, and visceral obesity of elderly patients with T2DM for 3 years. In addition, the hippocampal atrophy and arteriosclerosis were not deteriorated, suggesting the possibility of being effective for prevention of dementia.

Disclosure
M. Yoshida: None. T. Morimoto: None. E. Oh: None. N. Yamamoto: None. K. Nagata: None. A. Saeki: None. E. Sasaki: None. S. Yoshida: None. T. Kuzuya: None. N. Ohsawa: None. M. Sugino: None.
Sodium-Glucose Cotransporter 2 Inhibitors for Type 1 Diabetes Mellitus—Systematic Review and Meta-analysis
Authors: YAMADA TOMOHIDE , HOSOE JUN , SHOJIMA NOBUHIRO , YAMAUCHI TOSHIMASA , KADOWAKI TAKASHI 
Published: June 2018

Additional treatment for type 1 diabetes is an unmet need. We investigated the efficacy and safety of adding Sodium-glucose co-transporter 2 inhibitors (SGLT2is) to insulin in patients with type 1 diabetes mellitus by performing meta-analysis. Prospective randomized, placebo-controlled trials investigating insulin and SGLT2is in adults with type 1 diabetes were assessed. We searched electronic databases up to November 2017. Meta-analysis was performed by a random effects model. Two reviewers independently extracted information and evaluated study quality with the Cochrane risk-of-bias tool. Among about 1300 studies identified, 14 studies were investigated (N=4,591). Meta-analysis revealed that SGLT2i therapy significantly reduced HbA1c by 0.4% (95% confidence interval [CI]: 0.35, 0.46; P&lt;0.001; I2=0%), fasting plasma glucose by 1.14 mmol/l (0.8,1.47), body weight by 2.68 kg (2.0, 3.36), and systolic blood pressure by 3.37 mmHg (1.46, 5.28). In addition, the total daily insulin dose decreased by 6.0 units (4.9, 7.1), bolus insulin decreased by 3.6 units/day (2.0, 5.3), and basal insulin decreased by 4.2 units/day (2.2, 6.3). There was no significant increase of hypoglycemia or severe hypoglycemia. However, SGLT2i therapy increased diabetic ketoacidosis [OR: 3.38 (1.74, 6.56)] and genital tract infection [OR: 3.44 (2.34, 5.07)].
In summary, SGLT2i therapy might be advantageous for type 1 diabetes. However, use of this combination should be considered carefully.

Disclosure
T. Yamada: None. J. Hosoe: None. N. Shojima: None. T. Yamauchi: Research Support; Self; Novo Nordisk Inc., Daiichi Sankyo Company, Limited, Sanofi, Takeda, Tanabe-Mitsubishi. T. Kadowaki: Consultant; Self; Novo Nordisk A/S, AstraZeneca, Merck Sharp & Dohme Corp.. Research Support; Self; Kissei Pharmaceutical Co., Ltd., Taisho Pharmaceutical Co., Ltd., Sanofi, Kyowa Hakko Kirin Co., Ltd., Novo Nordisk A/S, Astellas Pharma, Daiichi Sankyo Company, Limited, Takeda, Mitsubishi Tanabe Pharma Corporation, Ono Pharmaceutical Co., Ltd., Merck Sharp & Dohme Corp., Nippon Boehringer Ingelheim Co. Ltd.. Speaker's Bureau; Self; Astellas Pharma, AstraZeneca, Merck Sharp & Dohme Corp., Ono Pharmaceutical Co., Ltd., Takeda, Eli Lilly and Company, Nippon Boehringer Ingelheim Co. Ltd., Novo Nordisk A/S.
Ipragliflozin, a SGLT2 Inhibitor, Reduced Body Weight and Fat Mass but Not Muscle Mass in Japanese Type 2 Diabetic Patients Treated with Insulin—A Randomized Clinical Trial
Authors: MORINO KATSUTARO , INOUE HIDEKA , FUSE KEIKO , TANAKA SACHIKO , KONDO KEIKO , ARIMA HISATOMI , MIURA KATSUYUKI , SATO DAISUKE , OHASHI NATSUKO , IDA SHOGO , MIYAZAWA ITSUKO , SEKINE OSAMU , UGI SATOSHI , MAEGAWA HIROSHI ,   SUMS-ADDIT-1 STUDY GROUP
Published: June 2018

Objective: Weight gain is a common problem in the insulin treatment. SGLT2 inhibitors are expected to reduce body weight (BW) due to negative energy balance. Previous reports suggested that BW reduction is achieved mainly by loss of body fat, and ∼20% of reduction is by lean mass. However, the efficacy of SGLT2 inhibitor on BW and body composition remains unclear. We examined these in the Japanese T2DM treated with insulin.
Methods: The study was an open label randomized controlled trial. Primary endpoint was the change in BW from baseline to week 24 between the two groups. Fifty overweight patients (BMI &gt; 23) who had inadequate glycemic control with insulin treatment were randomly assigned to ipragliflozin (Ipra) or standard treatment (Con) and followed for 24 weeks. Body composition was assessed by DEXA and impedance method.
Results: The change in BW was significantly larger in Ipra compared to Con. Ipra showed significant larger reduction of HbA1c. Total fat mass was reduced in the Ipra compared to Con mainly due to lower limb fat and trunk fat. Total muscle mass was maintained at lower limbs and trunk but tended to be reduced at arm in Ipra.
Conclusion: Ipragliflozin treatment for 24 weeks resulted in reduction of BW mainly due to fat mass at lower limb and trunk. Reduction of the muscle mass at lower limb may be protected by anti-gravity effect.

Disclosure
K. Morino: Research Support; Self; Astellas Pharma US, Inc., AstraZeneca, Sunstar Inc., CMIC Pharmascience, Kowa Pharmaceutical. H. Inoue: None. K. Fuse: None. S. Tanaka: None. K. Kondo: None. H. Arima: Advisory Panel; Self; Kyowa Kirin. Speaker's Bureau; Self; Takeda Japan, Daiichi Sankyo Company, Limited. K. Miura: None. D. Sato: None. N. Ohashi: None. S. Ida: None. I. Miyazawa: None. O. Sekine: None. S. Ugi: Research Support; Self; Boehringer Ingelheim Pharmaceuticals, Inc., MSD K.K. H. Maegawa: Speaker's Bureau; Self; Astellas Pharma US, Inc.. Research Support; Self; Astellas Pharma US, Inc.. Speaker's Bureau; Self; Mitsubishi Tanabe Pharma Corporation. Research Support; Self; Mitsubishi Tanabe Pharma Corporation. Speaker's Bureau; Self; Sanofi. Research Support; Self; Sanofi. Speaker's Bureau; Self; Nippon Boehringer Ingelheim Co. Ltd.. Research Support; Self; Nippon Boehringer Ingelheim Co. Ltd.. Speaker's Bureau; Self; Daiichi Sankyo Company, Limited. Research Support; Self; Daiichi Sankyo Company, Limited, Takeda Pharmaceutical Company. Speaker's Bureau; Self; Takeda Pharmaceutical Company, Novo Nordisk A/S, Eli Lilly and Company.
The Effect of Empagliflozin on Metabolic Parameters in Nonobese Nondiabetic Model of Metabolic Syndrome
Authors: TRNOVSKA JAROSLAVA , HÜTTL MARTINA , MARKOVÁ IRENA , OLIYARNYK OLENA , MALINSKA HANA , KAZDOVA LUDMILA , HALUZIK MARTIN 
Published: June 2018

Empagliflozin (EMPAG), an SGLT2 inhibitor, improves glucose metabolism by increasing urinary glucose output. EMPA-REG OUTCOME study documented cardiovascular (CV) benefits of EMPAG in patients with type 2 diabetes (T2DM) and history of a CV event. This work was undertaken to investigate complex effects of EMPAG in hereditary hypertriglyceridemic rats (HHTg), a non-obese, nondiabetic model of metabolic sydrome. HHTg rats are characterized by the presence of dyslipidemia and insulin resistance without obesity or hyperglycemia. 8 months old male HHTg rats were fed a standard diet (SD) or SD enriched by EMPAG in a dose of 10 mg/kg body weight/day for 6 weeks. EMPAG treatment suppressed an increase in body weight despite greater average food intake in EMPAG relative to control group. EMPAG administration induced glycosuria (+99%; P&lt;0.001) and decreased fasting glycemia (-21%; P&lt;0.02). Plasma lipid profile in postprandial state revealed a decrease in triglycerides (-34%; P&lt;0.001) and insulin (-36%;P&lt;0.01), increase in HDL cholesterol (+17%; P&lt;0.01) and free fatty acids (+36%; P&lt;0.02). Systemic ketone bodies concentrations were unchanged with simultaneous decrease in 14C-palmitic acid oxidation in the myocardium suggesting ketone bodies utilization by this tissue. EMPAG improved parameters of oxidative stress (SOD: +24%; P&lt;0.03; GSH-Px: +31%; P&lt;0.01; TBARS: -17%; P&lt;0.003) in the kidney and decreased glycogen content in the liver and muscle by 39% and 13%; respectively (P&lt;0.01). EMPAG improved insulin sensitivity of white adipose tissue (+13%; P&lt;0.05) and decreased relative weight of perirenal adipose tissue (-13%; P&lt;0.01).
In conclusion, in nondiabetic rats with MS, EMPAG improved insulin sensitivity of WAT, dyslipidemia and oxidative stress in the kidney. Combination of these factors may partially explain CV benefits of EMPAG in T2DM and suggests the possibility of similar benefits in patients with metabolic syndrome without diabetes.

Disclosure
J. Trnovska: None. M. Hüttl: None. I. Marková: None. O. Oliyarnyk: None. H. Malinska: None. L. Kazdova: None. M. Haluzik: None.
Adiponectin Attenuates NLRP3 Inflammasome by Modulating AMPK-ROS Pathway
Authors: WANG FANG , WANG LINGHAO , LIU YUXING , YUAN JINGJING , MO ZHAOHUI 
Published: June 2018

Adiponectin is an adipocyte-derived cytokine that exerts antidiabetic and anti-atherogenic properties and has been shown to enhance insulin sensitivity and promote lipid metabolism in obesity-linked diseases through the anti-inflammatory action. However, the detail mechanism of the anti-inflammatory effect of adiponectin remains unknown. In the present study, we found that in 50 patients with newly diagnosed type 2 diabetes (T2D), the circulating levels of adiponectin correlate inversely with IL-18 (r = -0.64, P &lt; 0.01). On this basis and in vitro, we demonstrated that adiponectin significantly attenuates IL-18 secreation from LPS+PA-induced THP-1 cells (P &lt; 0.01). In addition, we reported here that adiponectin inhibits IL-18 by suppressing NLRP3 inflammasome activation. Importantly, we found that adiponectin suppressed LPS+PA (palmitic acid)-induced ROS production, which is required for NLRP3 inflammasome activation. Furtherly, we, for the first time, described that adiponectin attenuates NLRP3 inflammasome activation by modulating AMPK-ROS signaling pathway, as the reason that suppression of AMPK with small interfering RNA (siRNA) abolished adiponectin-mediated inhibition of ROS and NLRP3 inflammasome. In vivo studies with STZ-induced diabetic mice models, we showed that adenovirus-mediated overexpression of adiponectin decreased triglycerides and cholesterol in the serum of diabetic mice. Meanwhile, adiponectin decreased CD68 positive macrophages infiltrated in adipose tissue. Furthermore, adiponectin reduced activation of NLRP3 inflammasome in liver and white adipose tissue (WAT) with western blot assay. Taken together, we report a new mechanism that adiponectin alleviates inflammation through NLRP3 inflammasome inhibition by modulating AMPK-ROS pathway, which may have therapeutic implications for T2D and the related metabolic diseases.

Disclosure
F. Wang: None. L. Wang: None. Y. Liu: None. J. Yuan: None. Z. Mo: None.
Modeling Long-Term Cost-Effectiveness of Sitagliptin and SGLT2i Combination Therapy for the Treatment of Type 2 Diabetes
Authors: PAWASKAR MANJIRI , PINAR BILIR S. , GRABER-NAIDICH ANNA , GONZALEZ CLAUDIO D. , RAJPATHAK SWAPNIL , DAVIES GLENN M. 
Published: June 2018

Clinical benefits of dipeptidyl peptidase-4 inhibitors (DPP-4i) and sodium-glucose co-transporter 2 inhibitors (SGLT2i) combination therapy have been demonstrated through clinical trials; however, there is limited understanding of economic benefits of sequential use of these therapies. This study evaluated the long-term cost-effectiveness of a treatment strategy involving intensification with SGLT2is (pathway 1) compared to NPH insulin (pathway 2) in type 2 diabetes (T2D) patients not at goal on metformin and sitagliptin therapy in the UK. The QuintilesIMS CORE Diabetes Model was used to perform cost-effectiveness analysis over a patient’s lifetime. Treatment effect data were obtained from randomized clinical trials, and economic data were obtained from multiple published sources. Several scenario analyses were performed to assess the robustness of base case results. Pathway 1 increased total life years (13.49 vs. 13.37, respectively) and quality-adjusted life years (QALY) (9.40 and 9.22, respectively) compared to pathway 2. Although drug costs in pathway 1 were higher than pathway 2, they were offset by decreases in diabetes-related complications and body mass index, leading to lower total direct medical costs for pathway 1 (£25,747 vs. £26,095). Thus, pathway 1 dominates pathway 2, as it is both more effective and less costly. Results from scenario analyses assessing changes in treatment effect, hypoglycemia rate, body mass index, cardiovascular protective effect of SGLT2i consistently showed that pathway 1 was either dominant (incremental cost effectiveness ratio (ICER) &lt;$0/QALY) or cost-effective [(ICER &lt; £3,000/QALY for patients with lower baseline HbA1c (7%) or older age (65+years)]. Among patients not at goal on metformin and sitagliptin therapy, treatment intensification with SGLT2i is likely to be cost effective compared to intensification with NPH insulin as 3rd line therapy in T2D in the UK.

Disclosure
M. Pawaskar: Employee; Self; Merck & Co., Inc. S. Bilir: Consultant; Self; Merck & Co., Inc.. A. Graber-Naidich: None. C.D. Gonzalez: Employee; Self; Merck & Co., Inc. S. Rajpathak: Employee; Self; Merck & Co., Inc. G.M. Davies: Employee; Self; Merck & Co., Inc..
Assessing the Value of Canagliflozin (CANA) vs. Sitagliptin (SITA) as Second-Line Therapy in the U.S.—The Importance of Considering Evidence from the CANVAS Program
Authors: WILLIS MICHAEL , NESLUSAN CHERYL , NILSSON ANDREAS , ASSEBURG CHRISTIAN 
Published: June 2018

Efficient allocation of health care resources requires choosing treatments that provide good “value for money”, which for chronic and progressive diseases like diabetes requires long-term modeling. For patients not controlled on metformin (MET), the ADA’s Standards of Medical Care recommend that “drug-specific effects and patient factors” guide the choice of next agent and that those with atherosclerotic CVD receive treatment with agents with evidence of CV risk reduction. The SGLT2 inhibitors CANA and empagliflozin have shown such a benefit, unlike the DPP-4s. The objective of this analysis was to estimate the cost-effectiveness of CANA vs. SITA as add-on to MET from the U.S. 3rd party payer perspective. A comprehensive health economics model (ECHO-T2DM) was used to estimate health and cost consequences over 30 years. Baseline patient characteristics and biomarker changes were sourced from a previously reported head-to-head study of CANA vs. SITA as add-on to MET. Hazard ratios from the CANVAS Program for myocardial infarction (MI), stroke, heart failure hospitalization, and CV mortality were used to capture effects not mediated by changes in biomarkers (i.e., HbA1c, SBP, weight). Progression of DKD incorporated eGFR findings from the CANVAS program. In addition, adverse events associated with CANA were included in the simulations. Costs of health events and associated impacts on Quality-Adjusted Life Years (QALYs) were sourced from the literature. In the base case, use of CANA vs. SITA resulted in cost savings ($7,401), as well as increased longevity (0.48 years) and QALYs (0.46). The largest contributors to savings were antihyperglycemic drug costs (given less therapy intensification to maintain glucose control) and treatment costs associated with delayed DKD progression and MIs. These results suggest that the use of CANA vs. SITA as 2nd line therapy will improve health outcomes at a reduced cost.

Disclosure
M. Willis: Other Relationship; Self; Janssen Global Services, LLC. C. Neslusan: Employee; Self; Janssen Global Services, LLC. A. Nilsson: Other Relationship; Self; Janssen Global Services, LLC. C. Asseburg: Other Relationship; Self; Janssen Global Services, LLC..