bluuebunny/crossref_metadata_2025 huggingface dataset:
1164-P: Effects of Cenicriviroc in Adults with NASH on Inflammatory Cytokines and Metabolic Parameters
Authors: COVIELLO ANDREA D. , CHARLTON RALPH W. , MARTINS EDUARDO B. , YUAN JIACHENG , ALKHOURI NAIM , ABDELMALEK MANAL F.
Published: June 2019

Background: Hepatic fat accumulation modulates innate immunity causing recruitment of bone marrow derived macrophages/activation of Kupffer cells, resulting in inflammatory changes associated with the development of insulin resistance and NASH. Monocyte recruitment/infiltration into the liver is mediated by C-C chemokine receptor 2 (CCR2). CCR5 promotes obesity-induced insulin resistance/hepatic steatosis in murine models. Cenicriviroc (CVC) is an oral CCR2/CCR5 antagonist in Phase 3 development for NASH. We evaluated effects of CVC on inflammatory cytokines and HbA1c in NASH subjects.

Methods: Adults with NASH and liver fibrosis were randomized 1:1 to CVC 150 mg or placebo (PBO) [Phase 2 CENTAUR study]. Cytokines and metabolic parameters were assessed.

Results: In 289 randomized adults (mean age 54 years, mean BMI 33.9 kg/m2, 52.0% diabetes), CCL2 significantly increased from baseline (BL) in CVC vs. PBO. For CVC, hs-CRP, IL-6, IL-8 and IL-1β decreased from BL; HbA1c decreased for CVC at all time points but increased for PBO at Days 180 and 360 (Table). Changes were consistent over time and more pronounced in those with advanced liver fibrosis.

Conclusions: CVC was associated with elevation of CCL2 and decreased hs-CRP/inflammatory cytokines, suggesting strong target engagement and a therapeutic impact on the inflammatory milieu associated with insulin resistance that may be reflected in lower HbA1c.

Disclosure

A.D. Coviello: Consultant; Self; Novo Nordisk Inc. Research Support; Self; Allergan, Bristol-Myers Squibb Company, GENFIT. Speaker's Bureau; Self; Novo Nordisk Inc. R.W. Charlton: Employee; Self; Allergan. E.B. Martins: Employee; Self; Allergan. Stock/Shareholder; Self; Allergan. J. Yuan: None. N. Alkhouri: Speaker's Bureau; Self; Gilead Sciences, Inc., Intercept Pharmaceuticals, Inc. Other Relationship; Self; Allergan, GENFIT, Gilead Sciences, Inc., Intercept Pharmaceuticals, Inc., Madrigal. M.F. Abdelmalek: Advisory Panel; Self; Allergan, Bristol-Myers Squibb Company, Madrigal Pharmaceuticals, NGM Biopharmaceuticals, Prometic Life Sciences Inc. Consultant; Self; TaiwanJ Pharmaceuticals Co., Ltd. Research Support; Self; Akcea Therapeutics, Allergan, Boehringer Ingelheim Pharmaceuticals, Inc., Bristol-Myers Squibb Company, Conatus Pharmaceuticals Inc., Galectin Therapeutics Inc., GENFIT, Gilead Sciences, Inc., Intercept Pharmaceuticals, Inc., Madrigal Pharmaceuticals, NGM Biopharmaceuticals, Novartis Pharmaceuticals Corporation, Prometheus, Shire, TaiwanJ Pharmaceuticals Co., Ltd. Speaker's Bureau; Self; Alexion Pharmaceuticals, Inc.
117-LB: DIWHY: Factors Influencing Motivation, Barriers, and Duration of DIY Artificial Pancreas System Use among Real-World Users
Authors: BRAUNE KATARINA , O’DONNELL SHANE , CLEAL BRYAN , LEWIS DANA M. , TAPPE ADRIAN , HAUCK BASTIAN , WILLAING INGRID , SCIBILIA RENZA , ROWLEY ELIZABETH , KO WINNE , DOYLE GERARDINE , SKINNER TIMOTHY C. , RAILE KLEMENS ,   THE OPEN CONSORTIUM
Published: June 2019

Objective: Little is known about why PwD leave traditional pathways and turn to DIY technology. This study aims to examine the motivations of Do-it-Yourself Artificial Pancreas System (DIYAPS) users and caregivers to build and maintain these systems.

Methods: An online survey with 34 items was distributed to DIYAPS users and caregivers of children with DIYAPS through Facebook (“Looped” and regional subgroups) and Twitter (Diabetes Online Community).

Results: 1058 participants from 34 countries responded to the survey. The majority were adult users (80.2%; 43% female; median age 41 years) with T1D (98.9%) for 25.2 years ±13.3. 19.8% were caregivers of children (47.4% female; median age 10 years) with T1D (99.4%) for 5.1 years ±3.9. With 10.1m ±17.6 on DIYAPS, HbA1c improved from 7.07% ±1.07 to 6.24% ±0.68 %. Time in Range improved from 63.21% ±16.27 to 83.07% ±10.11. Additional out-of-pocket costs of 712 USD/year were spent. Motivations to build a DIYAPS are shown in Fig.1.

Conclusions: Improved glycemic control, need for an ‘autopilot’ and less acute and long-term complications were key motivations in both groups; as well as better sleep for caregivers. Users were also able to access and afford the required tools. These results may provide a better understanding of unmet needs of PwD and current challenges to uptake, in order to facilitate the involvement of patient-led and open source approaches in healthcare.

Disclosure

K. Braune: Advisory Panel; Self; Medtronic MiniMed, Inc. Speaker’s Bureau; Self; Dexcom, Inc. S. O’Donnell: None. B. Cleal: None. D.M. Lewis: Consultant; Self; Diabeloop SA, Roche Diabetes Care. A. Tappe: Consultant; Self; IME-DC GmbH. Employee; Self; Hi.health, Gruber-Debong GmbH. Speaker’s Bureau; Self; Dexcom, Inc., Roche Diabetes Care, Ypsomed AG. Other Relationship; Self; SOOIL Developments Co., Ltd. B. Hauck: Consultant; Self; Bayer AG, Eli Lilly and Company, LifeScan, Inc., Novo Nordisk A/S, Roche Diabetes Care, Roche Pharma. I. Willaing: None. R. Scibilia: Speaker’s Bureau; Self; Roche Diabetes Care. E. Rowley: None. W. Ko: None. G. Doyle: None. T.C. Skinner: None. K. Raile: Advisory Panel; Self; Abbott, Lilly Diabetes.

Funding

European Union
1170-P: Alleviation Effects of a Traditional Chinese Medicine on Diabetes in Rats Linked to Modulation of the Gut Microbiome
Authors: TIAN JIAXING , LI MIN , TONG XIAOLIN
Published: June 2019

Introduction: Gegen Qinlian Decoction (GQD) is a Chinese herbal medicine that has been reported to significantly decrease blood glucose levels, which is suggested to be related to interactions with the gut microbiota. However, the protective effect of GQD on intestinal barrier function with regard to its influence on the gut microbiota has not been explored to date. In this study, we investigated the role of the gut microbiota in mediating the hypoglycemic mechanism of GQD in type 2 diabetes mellitus (T2DM) rats.

Methods: The T2DM rats were randomly allocated to receive GQD, metformin (Met), or distilled water for 12 consecutive weeks, and changes in metabolic parameters, intestinal barrier function, and inflammation were investigated. Gut microbiota were analyzed using 16S rRNA sequencing from fecal samples, and statistical analyses were performed to correlate microbiota composition with phenotypes of the T2DM rats.

Results: Both GQD and Met administration decreased the levels of blood glucose and inflammatory factors, and increased the levels of tight junction proteins. However, GQD had a greater protective effect on islet function, restoring intestinal permeability, and inhibiting inflammation than Met, as evidenced by improvements in the levels of occludin and claudin-1 in the colon, and the expressions of serum inflammatory factors. In addition, GQD regulated the structure of the gut microbiota by increasing the proportions of short-chain fatty acids-producing and anti-inflammatory bacteria, and decreasing the proportions of conditioned pathogenic bacteria associated with the diabetic phenotype.

Conclusion: GQD could ameliorate hyperglycemia and protect islet function by regulating the structure of the gut microbiota, thereby restoring intestinal permeability and inhibiting inflammation in T2DM rats. Our study thus suggests that the hypoglycemic mechanism of GQD is mediated by its modulation of the gut microbiota.

Disclosure

J. Tian: None. M. Li: None. X. Tong: None.

Funding

National Natural Science Foundation of China (81430097); China Association for Science and Technology (CACM-2017-QNRC1-02)
1171-P: Effect of Genetic Testing for Weight Loss on Adult Patients
Authors: JAMES KATHY S.
Published: June 2019

Background: It is well-known in obesity research and clinical practice that there are differing responses to dietary interventions.

Genetic evaluation based on metabolic genotypes has been found helpful in understanding which dietary and activity recommendations are a best fit for weight management.

Purpose: This study provided information on practicality, acceptability, and effectiveness of incorporating Genetic Influenced to Personalize Dietary and Exercise Plans (GIPDEP) in clinical practice. We assessed the efficacy of personalized weight loss recommendations based on genetic information compared to conventional care.

Sample: Patients (N=92; on average 47 years of age [range: 22 to 71]; 78 females; 3 with normal weight, 27 overweight, 62 obese) from a community-based weight loss clinic were randomly assigned to the treatment (51 received genotype test screening) and the control (40 received conventional care) groups stratified by age, gender, initial BMI, and score in the Weight Efficacy Lifestyle (WEL) scale. Measures: The Weight Efficacy Lifestyle questionnaire ([WEL] was used to assess confidence in ability to lose weight. Patients were assessed twice (beginning, 4-month follow-up).

Results: At four months, both groups showed comparable decrease in BMI (treatment: Δ(ΒΜΙ)=-0.87±2.06; control: Δ(ΒΜΙ)=-0.81±1.54; Wilcoxon Rank Sums test, p=0.908). Multiple regression was used to assess the effect of treatment on Δ(ΒΜΙ) adjusting for age, gender, exercise, health issues limiting exercise, and daily sleep. In all models, treatment was not a statistically significant predictor of Δ(ΒΜΙ) (all p > 0.50).

Summary: Results do not provide evidence that weight loss recommendations based on genetic screening are more advantageous than conventional recommendations. The non-finding may be explained if we consider that weight loss is associated with a number of factors, i.e., self-efficacy, support, etc. The advantage of optimal recommendations may be masked by these other factors.

Disclosure

K.S. James: None.

Funding

Allen Foundation Inc.
1174-P: Improvements of Insulin and Leptin Sensitivity for Type 2 Diabetes and Obesity by Cyclo-(His-Pro) plus Zinc Treatment
Authors: SONG MOON K.
Published: June 2019

Cyclo (his-pro) plus zinc (Cyclo-Z) treatment improved insulin and leptin sensitivity without any known side effects in animal studies. We now report the results of a randomized, double-blind, placebo-controlled multicenter FDA approved phase 2a clinical trial with obese diabetic subjects. A total of 64 subjects with hemoglobin A1c (HbA1c) levels between 7.5 and 10 and body mass index (BMI) above 30 were recruited in 4 different treatment groups: A:3 mg CHP, B:9 mg CHP; or C:15 mg CHP plus 23 mg zinc in all three treated groups; D: placebo to take one capsule by every subject at bedtime daily. HbA1c, OGTT, plasma insulin and leptin levels, were determined every 4 weeks while body weight, BMI and side effects were determined every 2 weeks. During the 12-week study period, HbA1c levels changed from baseline at 12 weeks as A: -0.247 ± 0.198 %; B: -0.233± 0.282%; C: -0.586± 0.250%; D: 0.05 ± 0.248%. p=0.0824 C vs. D. Body weight changed. A:0.479 ± 1.032 kg; B: 0.738 ± 0.784 kg ; C: -0.962 ± 0.6 29 kg ; D: 1.456 ± 0.772 kg. P=0.0249 C vs. D. TAFGC (OGTT) changed. A: -2.675 ± 10.336 mg/dL/hour; B: -2.399 ± 8.197 mg/dL/hour; C: -14.895 ±5.751mg dL/hour; D:0.8475 ± 13.515 mg/dL/hour. p=0.039 C vs. D. BMI changed. A: -0.089± 0.358 kg/m2; B: 0.008± 0.186 kg/m2; C: -0.291 ± 0.186 kg/m2; D:1.023 ± 0.493 kg/m2. P=0.049 C vs. D. Plasma insulin levels changed. A:4.269 ± 8.115 µU/mL; B: 2.787 ± 2.566 µU/mL; C: -5.0 ± 10.795 µU/mL; D: 29.787± 28.513 µU/mL. P=0.0296 C vs. D. Plasma leptin levels changed. A:0.25 ± 1.065 ng/mL; B: -3.42 ± 1.488 ng/mL; C: -3.386± 0.784 ng/mL; D:0.377 ± 1.12 ng/mL. P=0.010 C vs. D. No Adverse side effects were detected in any group. Cyclo-Z containing 15 mg CHP plus 23 mg zinc appears to be the most effective dose and safe for the treatment for both diabetes and obesity through improving insulin resistance and leptin resistance. FDA IND:061897.

Disclosure

M.K. Song: Stock/Shareholder; Self; NovMetapharma Inc in Korea (Investor company).

Funding

NovMetaPharma Co., Ltd.
1182-P: A Selective Nonpeptide Somatostatin Receptor 5 (sst5) Agonist Effectively Decreases Insulin Secretion in the KATPHI Mouse Model
Authors: JULIANA CHRISTINE , CHAI JINGHUA , RICO-BAUTISTA ELIZABETH F. , BETZ STEPHEN F. , DE LEON DIVA D.
Published: June 2019

Inactivating mutations of β-cell KATP channels cause the most common and severe form of congenital hyperinsulinism (HI), a β-cell disorder that causes dysregulated insulin secretion and persistent hypoglycemia. Children with KATPHI are typically unresponsive to diazoxide, the only FDA-approved drug for HI. Octreotide, a sst2 peptide agonist that inhibits insulin secretion, is used as second line therapy, but poor efficacy and sst2-mediated side effects, such as glucagon suppression and necrotizing enterocolitis, limit its use in infants. Thus, most infants with KATPHI require pancreatectomy for intractable hypoglycemia. To address the unmet need for effective and safe therapies, we examined the ability of a selective sst5 nonpeptide agonist CRN02481 (Crinetics Pharmaceuticals) to suppress insulin secretion and prevent fasting hypoglycemia in the SUR1-/- mouse model of KATPHI. SUR1-/- mouse islets were treated with CRN02481 (100 nM) or vehicle and then stimulated with a physiologic amino acid mixture (4 mM). CRN02481 significantly decreased baseline (1.5 ± 0.2 vs. 2.4 ± 0.5 ng/uL, p≤0.01) and amino acid-stimulated (2.8 ± 1.5 vs. 4.4 ± 1.1 ng/uL, p≤0.05) insulin secretion. SUR1-/- mice were gavaged with CRN02481 (10 mg/kg/day) or PBS for 7 days (n=7/group) and fasting glucose, glucose tolerance and insulin tolerance tests were assessed. CRN02481 significantly increased fasting glucose and prevented fasting hypoglycemia (98 ± 18 vs. 44 ± 6 mg/dL, p<0.00001). During a glucose tolerance test CRN02481 increased post-glucose load glucose concentrations significantly by 60 and 90 minutes. CRN02481 significantly decreased the slope of decline of glucose concentrations after insulin administration (1 u/kg): -2.8 ± 2.3 vs. -5.7 ± 2.1, p=0.03). Collectively these data show that the sst5 agonist CRN02481 effectively suppresses insulin secretion and prevents fasting hypoglycemia in the KATPHI mouse model and is a potentially novel therapy for children with HI.

Disclosure

C. Juliana: Research Support; Self; Crinetics. J. Chai: None. E.F. Rico-Bautista: Employee; Self; Crinetics Pharmaceuticals. Stock/Shareholder; Self; Crinetics Pharmaceuticals. S.F. Betz: Employee; Self; Crinetics Pharmaceuticals. Stock/Shareholder; Self; Crinetics Pharmaceuticals. D.D. De Leon: Consultant; Self; Crinetics, Novartis Pharmaceuticals Corporation, ProSciento, Soleno Therapeutics, Zealand Pharma A/S. Employee; Spouse/Partner; Merck & Co., Inc. Research Support; Self; Crinetics, Dexcom, Inc., Zealand Pharma A/S. Stock/Shareholder; Self; Merck & Co., Inc.

Funding

Crinetics Pharmaceuticals (to D.D.D.)
1184-P: Efficacy of Hydroxychloroquine (HCQ) 400mg in Patients with Poorly Controlled Insulin-Treated Type 2 Diabetes Mellitus
Authors: AHMED RISHAD , SHARMA AMIT BHUSHAN , NATARAJAN A. , AGARWAL DINESH , NARAYANAN A. SHANKAR
Published: June 2019

Objective: We retrospectively investigated the effects of adding HCQ 400 mg in patients with type 2 diabetes showing sub-optimal control by basal insulin and other OHA therapy.

Method: This is an open label, parallel group, retrospective and multicentre observational study. 123 patients with poorly controlled type 2 diabetes (baseline HbA1c 8.5 ± 0.6%) who are on basal insulin (glargine) with other OHA therapy (metformin 1gm+Sitagliptin 100 mg), were given HCQ 400 mg in addition to insulin. FPG, PPG and HbA1c values, daily insulin dose, body weight and the number of hypoglycemic events were recorded at weeks 0, 12 and 24.

Result: HbA1c decreased by 1.6%, from 8.5 ± 0.6% to 6.9 ± 0.8% (P<0.0001) at 24 weeks. FPG and PPG was reduced significantly from 223.7 ± 31 to 121± 19 mg/dl and from 313.2 ± 41 to 161± 21 mg/dl at the end of 24 week (P<0.0001). Required insulin dose was reduced significantly from 29.4 ± 14.5 to 22.1 ± 12.1 units/day (P= 0.0187). Body weight decreased significantly from 69.5 ± 5.2 to 67.0 ± 6.7 kg, (P= 0.0232). Numbers of hypoglycemic events per patient per month were 0.25 ± 0.35. No severe hypoglycemia occurred during the study period. 56% patients achieved HbA1c ≤ 7% at 24 weeks.

Conclusion: Administration of HCQ 400 mg resulted in sustained improvement in glycemic control when given as an adjunct to insulin therapy in patients with poorly controlled type 2 diabetes.

Disclosure

R. Ahmed: None. A. Sharma: None. A. Natarajan: None. D. Agarwal: None. A. Narayanan: None.
1189-P: Effectiveness of Hydroxychloroquine (HCQ) 400 mg in Uncontrolled T2D Patients on Dual Therapy of Metformin and Sulfonylurea: A Real-World Experience in India
Authors: PURKAIT INDRANIL , PAREEK ANIL , PANNEERSELVAM ARUNACHALAM , MUKHOPADHYAY MONOJIT K. , KUMAR SHARAD , CHANDRATREYA SUJIT ARUN
Published: June 2019

Objective: Many T2D patients have inadequate glycemic control despite conventional therapy of dual OHAs. Treating such patients in developing countries is a challenge as newer drugs are comparatively costly or patients may have apprehensions for injectable insulin. Objective of this observational study was to evaluate effectiveness of add-on therapy of HCQ in these patients.

Methods: A prospective, observational, multi-centre study was conducted where 1,007 T2D patients (age between 18-65 years), uncontrolled on a combination of two OHAs, with HbA1c ≥7.5%, fasting blood glucose of ≥126 mg/dL or 2-hour blood glucose ≥200 mg/dL and body weight ≥60 kg were prescribed hydroxychloroquine sulphate 400 mg once daily for 24 weeks. Mean change in HbA1c, FBG, PPG, serum creatinine and lipid parameters were assessed.

Results: At week 24, significant reduction in HbA1c (1.29%), FBG (18%), PPG (23%), TC (9%), LDL-C (12%) and non-HDL-C (12%) was observed (p < 0.0001). At the end of 24 weeks, 36.8% patients achieved HbA1c target of <7%.

Conclusion: Hydroxychloroquine effectively improved glycemic and lipid parameters in uncontrolled T2D patients. It may emerge as a valuable therapeutic intervention for patients uncontrolled on two OHAs. Its beneficial effect on lipids may potentially translate to improved CV outcomes.

Disclosure

I. Purkait: Employee; Self; Ipca Laboratories Ltd. A. Pareek: Employee; Self; Ipca Laboratories Ltd. A. Panneerselvam: None. M.K. Mukhopadhyay: None. S. Kumar: Advisory Panel; Self; Abbott, Alere Inc., Alkem Laboratories, Eli Lilly and Company, Eris Lifesciences, Glenmark Pharmaceuticals Limited, Intas Pharmaceuticals Ltd., Johnson & Johnson, Lupin Pharmaceuticals, Inc., Novo Nordisk Inc., Sanofi-Aventis, Sun Pharma, Torrent Pharma, USV Private Limited, Wockhardt, Zydus Pharmaceuticals, Inc. Consultant; Self; AstraZeneca, Biocon, Boehringer Ingelheim Pharmaceuticals, Inc., Dr. Reddys Laboratories. S.A. Chandratreya: None.
1219-P: Enhanced Response in Serum Ketone Level in Men Compared with Women by Administration of SGLT2 Inhibitor
Authors: YOSHIDA AKIHIRO , MATSUBAYASHI YASUHIRO , NOJIMA TOSHIAKI , SUGANAMI HIDEKI , KAKU KOHEI , SONE HIROHITO
Published: June 2019

SGLT2 inhibitors (SGLT2is) reduce hyperglycemia and insulin levels via increased urinary glucose excretion (UGE). Reduced insulin triggers decreased tissue glucose disposal and increased lipid use followed by ketone production. The metabolic response to starvation, the production of beta-hydroxybutyrate (BHB), was reported to be influenced by sex and menopausal status in healthy persons. However, little is known of sex- and menopausal status-specific effects of SGLT2is on BHB. This study investigated the effect of the SGLT2i tofogliflozin on BHB according to sex and menopausal status in type 2 diabetes mellitus (T2DM). Analyzed were 190 T2DM patients taking tofogliflozin as initial monotherapy in a Phase 3 study. Baseline characteristics were: men (66%); premenopausal (7%) and postmenopausal women (27%), age (mean 58y), and mean HbA1c (7.8%), BMI (26kg/m2), BHB (69µmol/L) and eGFR (83mL/min/1.73m2). Sex- and menopausal status-specific differences were analyzed by multivariate analysis. Longer duration of diabetes and lower baseline HDL-C and adiponectin were noted in men while age and HbA1c, BMI, BHB and eGFR were identical between sexes. Increases in BHB at weeks 4 and 52 were: men, median +128%* and +64*, respectively (+ p<0.01 vs. baseline); women, +48* and +58*, respectively. Mean increases in the fasting free fatty acid-to-insulin ratio (FIR) at week 52 were +88%* for men and +53* for women. Reductions in HbA1c and fasting insulin and increases in UGE and free fatty acids at week 52 were similar between sexes. Multivariate analyses showed a greater increase in BHB at week 52 in men than in women, especially postmenopausal women. Further, FIR increased greater in men than in women. Finally, premenopausal women had a greater increase in BHB than postmenopausal women. Results suggest that the different degrees of BHB elevation between sexes via tofogliflozin may provide clinical insights into sex- and menopause-specific metabolic responses to increased lipid use via SGLT2is in T2DM.

Disclosure

A. Yoshida: Employee; Self; Kowa Pharmaceutical Co. Ltd. Y. Matsubayashi: None. T. Nojima: Employee; Self; Kowa Co., Ltd. H. Suganami: Employee; Self; Kowa Co., Ltd. K. Kaku: Advisory Panel; Self; Astellas Pharma Inc., AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Novo Nordisk A/S. Speaker's Bureau; Self; Eli Lilly and Company, Merck Sharp & Dohme Corp., Mitsubishi Tanabe Pharma Corporation, Ono Pharmaceutical Co., Ltd., Taisho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Company Limited. H. Sone: Research Support; Self; Astellas Pharma Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Daiichi Sankyo Company, Limited, Kowa Pharmaceutical Europe Co. Ltd., Kyowa Hakko Kirin Co., Ltd., Novo Nordisk Inc., Ono Pharmaceutical Co., Ltd., Taisho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Company Limited, Teijin Pharma Limited.
122-LB: iSage: Successful Basal Insulin Titration Managed by a Prescription-Only Digital Therapy for T2DM
Authors: GRDINOVAC KRISTINE , ROBBINS DAVID C. , LAVENBARG TERI A. , LEVIN PHILIP , SYSKO RYAN
Published: June 2019

Ideally, initiating and titrating basal insulin should quickly achieve A1C and fasting glucose targets without significant hypoglycemia. In practice, it’s often not so simple.

iSage Rx (iSage) is the first FDA-cleared digital therapy for basal insulin titration that is prescribed by providers and easily downloaded to patients’ mobile phones. In less than a minute, the provider personalizes their patient’s glycemic targets and configures a titration algorithm for use with any basal insulin. The iSage app automatically manages the patient’s titration plan and provides ongoing education regarding insulin administration.

We tested the efficacy of iSage in 27 T2DMs (59±7.6 year, 12M/15F). Entry criteria included T2DM patients treated solely with detemir, glargine or delgudec insulin, fluency in English, and generally healthy. T2DMs with stage 4 or 5 kidney disease, active malignancies, variable glucocorticoid doses, severe visual impairment and dementia were excluded. The study aims included changes in both insulin dose and A1C values while achieving low rates of hypoglycemia. The average (SD) starting and app-directed final doses of insulin were 33.6 (20) and 46.8 (27) U/d, p=0.047, respectively. Initial mean A1c was 8.2 (1.4)% that dropped to 7.3 (0.95)%, p=0.002 at study termination (79-139 days). Among those with an initial A1c >8.0, (mean A1c 9.3%) the final mean A1c was 7.4% (1.0) p=0.005. Of the 2,257 fasting blood glucose readings (BG) recorded in the mobile app, only 27 were <70 mg/dL (1.64% of total fasting BGs). Participants required almost no unexpected visits or phone consultations to manage their insulin doses.

The iSage digital therapy, while prescribed by a provider, requires minimal provider demands, is patient self-directed, and produces significant reductions in A1C with low rates of hypoglycemia.

Disclosure

K. Grdinovac: None. D.C. Robbins: None. T.A. Lavenbarg: None. P. Levin: Research Support; Self; MannKind Corporation, Novartis AG, Novo Nordisk Inc. Speaker’s Bureau; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Janssen Pharmaceuticals, Inc., Lilly Diabetes, Merck & Co., Inc., Sanofi. R. Sysko: Employee; Self; iSage Rx, LLC.

Funding

Amalgam Rx, Inc.; Blue KC
1227-P: GlycoMark 1,5-Anhydrocluitol Values in Patients Taking SGLT2 Inhibitors
Authors: FEREIDOUNI SAM S. , SHOWS THOMAS P. , LESSARD-CHAUDOIN CHANTELLE , BRABENTZ KIM , TENOPALA ROBERTO E. , DAHLEN JEFFREY R.
Published: June 2019

The GlycoMark test measures 1,5-anhydroglucitol (1,5-AG), which is an indicator of hyperglycemic excursions over the prior 1-2 weeks in patients with diabetes. Circulating serum levels of 1,5-AG decrease in response to significant hyperglycemia because glycosuria interferes with 1,5-AG reabsorption in the kidney tubules. Significant hyperglycemia and resultant glycosuria causes 1,5-AG levels to fall below the normal range (∼10 ug/mL), and persistent glycosuria is associated with very low 1,5-AG levels, less than or equal to 2 ug/mL. SGLT2 inhibitors elicit their effect by blocking glucose reabsorption, causing persistent glycosuria. A survey of clinical laboratory results in 2014 indicated that 13% of the GlycoMark 1,5-AG tests produced results of 2 ug/mL or less (unpublished, data on file). We hypothesized that the use of SGLT2 inhibitors (SGLT2i) would produce a high frequency of GlycoMark 1,5-AG results less than 2 ug/mL. A review of GlycoMark 1,5-AG measurements performed between January 2015 - April 2018 from 291 patients that were prescribed SGLT2i was performed. 35 patients were found to be non-compliant with their SGLT2i and were excluded from the analysis. From the remaining 256 patients taking SGLT2i, the average GlycoMark 1,5-AG level was 1.7 ug/mL and 87% of patients taking SGLT2 inhibitors had GlycoMark 1,5-AG values less than or equal to 2 ug/mL. The results of this analysis indicate that the majority of patients with diabetes that are taking SGLT2i have very low GlycoMark 1,5-AG results, which reflects the persistent glycosuria caused by the SGLT2i. In patients taking SGLT2i, a GlycoMark 1,5-AG result of 2 ug/mL may be useful as an indicator of the SGLT2i effect, particularly in patients with moderate to good glycemic control. Additionally, the average GlycoMark 1,5-AG level in the 35 non-compliant patients was 7.5 ug/mL, suggesting that GlycoMark test measurements above 2 ug/mL should be investigated for non-compliance, interference with, or reduced effectiveness of SGLT2i.

Disclosure

S.S. Fereidouni: Advisory Panel; Self; AstraZeneca, Janssen Pharmaceuticals, Inc. Consultant; Self; glycomark. Speaker's Bureau; Self; Amgen Inc., Janssen Pharmaceuticals, Inc., Merck & Co., Inc., Novo Nordisk Inc. T.P. Shows: None. C. Lessard-Chaudoin: None. K. Brabentz: None. R.E. Tenopala: None. J.R. Dahlen: Employee; Self; GlycoMark.
1233-P: Systematic Literature Review (SLR) and Network Meta-analysis (NMA) of SGLT-1/2 Inhibitors vs. Metformin (MET) as Add-On to Insulin in T1DM
Authors: LANGFORD BRYONY E. , EVANS MARC , HASKINS-COULTER TAO , O'CONNOR MARY-ELLEN , CANT HARRIET E. , EDDOWES LUCY A. , EDMONDS CHRISTOPHER , TANK AMARJEET
Published: June 2019

T1DM is characterized by deficient insulin production, requiring multiple daily insulin doses. However, glycemic control is often suboptimal, and insulin-associated weight gain and hypoglycemia are concerns. Therefore, adjunctive therapy may be beneficial. A SLR with searches conducted to 16 Oct 2018 identified phase III/IV RCTs of MET or SGLT1/2 inhibitors as add-on to insulin in T1DM. MEDLINE, Embase and the Cochrane Library were searched, as well as congresses, reference lists and grey literature. Bayesian NMAs were performed at Week 24/26 (Week 24) and Week 52 (Week 52) for change from baseline in HbA1c and weight, and the proportion of participants experiencing hypoglycemic events and hypoglycemic severe adverse events. Nine placebo (PBO) controlled RCTs of dapagliflozin (DAPA), MET, sotagliflozin (SOTA) or empagliflozin (EMPA) reporting results were included. There was some evidence of heterogeneity in study design and outcomes. Results of the NMAs for MET vs. comparator (Table) found that the SGLT2 and SGLT1/2 inhibitors generally performed better than MET for HbA1c and weight, but there were few significant differences for hypoglycemia at Week 52. Results suggest that adjunctive use of SGLT2 and SGLT1/2 inhibitors including DAPA can improve glycemic control compared to MET while enabling weight loss in T1DM, and demonstrate consistent efficacy for the class.

Disclosure

B.E. Langford: Employee; Self; Costello Medical. Research Support; Self; AstraZeneca. M. Evans: Research Support; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Janssen Pharmaceuticals, Inc., Merck Sharp & Dohme Corp., Mundipharma, Novartis Pharmaceuticals Corporation, Novo Nordisk Inc., Sunovion Pharmaceuticals Inc. T. Haskins-Coulter: Employee; Self; Costello Medical. M. O'Connor: Employee; Self; Costello Medical. H.E. Cant: Employee; Self; Costello Medical. L.A. Eddowes: Employee; Self; Costello Medical. C. Edmonds: Employee; Self; AstraZeneca. A. Tank: Employee; Self; AstraZeneca.

Funding

AstraZeneca; Cambridge University
1240-P: Differences in Initial Care and Outcomes Comparing Adults with Early vs. Usual Onset Type 2 Diabetes
Authors: BLATCHINS MARUTA A. , MISHRA PRANITA , GRANT RICHARD W. , GOPALAN ANJALI
Published: June 2019

The prevalence of newly diagnosed type 2 diabetes (T2D) among American adults under age 45 is increasing. Given the lasting benefits conferred by early glycemic control, we examined initial diabetes care and subsequent glycemic control at one year following diagnosis, comparing adults with early onset (21-<45 years old) vs. usual onset (45-<65 years old) T2D.

Using data from a large, integrated care delivery system, we identified adults who had a first diabetes-defining Hemoglobin A1c value (≥6.5% “index A1c”) between Jan. 2010 and Dec. 2016, followed by clinical diagnosis of T2D (visit with T2D ICD code or T2D on problem list) within 3 months of the index A1c. We excluded anyone with evidence of prior T2D, gestational diabetes or T1D. We compared baseline characteristics by onset age using t- or chi-2 tests. Adjusting for index A1c and other patient characteristics, we used logistic regression to examine initial management and GEE models to examine glycemic control (goal A1c <7%) at one-year following diagnosis, comparing early vs. usual age onset status.

We identified 32,137 adults with new T2D, including 8,496 with early onset (26.4%, age 37.6 ± 5.3 years) and 23,641 with usual onset (73.6%, age 54.4 ± 5.5 years). Adults with early onset had a higher index A1c (A1c 8.9% vs. 8.4% for usual onset, p<0.001). Compared to usual onset, adults with early onset were more likely to initiate metformin (adjusted odds ratio [aOR] 1.20, 95% CI [1.12-1.27]), but less likely to receive a retinal exam (aOR 0.80, 95% CI [0.76-0.85]) or diabetes-related education (aOR 0.84, 95% CI [0.80-0.89]) during the first year of care. Adults with early onset were less likely to achieve goal glycemic control at one year following diagnosis (aOR 0.85, 95% CI [0.79-0.91]).

In conclusion, individuals with early onset T2D were less likely to achieve goal A1c (<7%) at one year following diagnosis. This suggests a need for tailored strategies to improve early T2D care for this high-risk population of adults presenting with T2D at younger ages.

Disclosure

M.A. Blatchins: None. P. Mishra: None. R.W. Grant: None. A. Gopalan: None.

Funding

National Institute of Diabetes and Digestive and Kidney Diseases
125-OR: Child Growth Tracking and Type 2 Diabetes Risk: A Life Course Analysis
Authors: OLAIYA MUIDEEN T. , KNOWLER WILLIAM C. , HANSON ROBERT L. , KOBES SAYUKO , NELSON ROBERT , SINHA MADHUMITA
Published: June 2019

Background: Knowing vulnerable periods of growth for predicting type 2 diabetes (T2D) incidence may help focus interventions for prevention. Using life course data, we identified critical growth periods in childhood that predict T2D risk.

Methods: This analysis of a longitudinal study of American Indians, aged ≥ 5 years, comprised subjects representing three growth periods (pre-, early, and late adolescence). Age-sex-height-adjusted mean attained weight and weight velocity (change/year) were computed in each growth period. Subjects were followed from the end of each growth period until T2D diagnosis or their last research examination. Poisson regression was used to model the effects of the mean attained weight or weight velocity in a growth period on T2D incidence.

Results: There were 290 incident T2D cases among 2100 subjects representing the pre-adolescence growth period, 315 cases among 1558 in the early adolescence period, and 380 cases among 1418 in the late adolescence period. In each growth period, the mean attained weight significantly predicted T2D incidence, especially in the first 5 years of follow-up (Figure, A-C). There were significant effects of weight velocity in pre-adolescence and modest effects in late adolescence on T2D incidence (Figure, D-F). Attained weight pre-adolescence had the strongest effect on T2D incidence.

Conclusions: Pre-adolescence is an especially vulnerable period for predicting later T2D.

Disclosure

M.T. Olaiya: None. W.C. Knowler: None. R.L. Hanson: None. S. Kobes: None. R. Nelson: None. M. Sinha: None.

Funding

National Institute of Diabetes and Digestive and Kidney Diseases
1254-P: Increased Health-Care Resource Utilization (HRU) and Costs among Nonalcoholic Fatty Liver Disease/Nonalcoholic Steatohepatitis (NAFLD/NASH) Patients with Advanced Fibrosis (AF) having Diabetes Mellitus (DM)
Authors: GORDON STUART , KACHRU NANDITA , OZBAY A. BURAK , WONG ROBERT
Published: June 2019

Objective: NAFLD/NASH patients with AF (bridging fibrosis/F3 and compensated cirrhosis/F4) have an increased risk of liver disease progression leading to higher costs, which may be compounded by presence of DM. The study evaluated the impact of DM on HRU and associated healthcare costs among NAFLD/NASH-AF patients in the U.S.

Methods: Adult NAFLD/NASH-AF patients with available lab results were identified from 2008-2016 Optum Research claims database, to calculate their Fibrosis-4 (FIB-4) score. Using the FIB-4 score, patients were categorized as F3 or F4 (first date of FIB-4 cut-off score marked the index date), and then stratified by DM (ICD codes). Mean annual HRU/costs were obtained via per patient per month values (2016 USD).

Results: Among 91,122 NAFLD/NASH patients with FIB-4 scores, 2,482 (2.7%) had F3, among which 36% had DM, and 939 (1.0%) had F4, among which 35% had DM. The mean annual costs of F3 and F4 patients with DM were 12-53% higher than non-DM (Figure) before and after the development of AF.

Conclusions: NAFLD/NASH-AF patients with DM had higher mean annual HRU-associated costs compared to those without DM - primarily driven by ambulatory and pharmacy costs. Management options are needed to improve clinical care and optimize healthcare costs among NAFLD/NASH-AF patients with DM.

Disclosure

S. Gordon: Consultant; Self; Gilead Sciences, Inc., Intercept Pharmaceuticals, Inc. N. Kachru: Employee; Self; Gilead Sciences, Inc. Stock/Shareholder; Self; Gilead Sciences, Inc. A. Ozbay: Employee; Self; Gilead Sciences, Inc. Stock/Shareholder; Self; Gilead Sciences, Inc. R. Wong: Advisory Panel; Self; Gilead Sciences, Inc. Consultant; Self; Gilead Sciences, Inc. Research Support; Self; Gilead Sciences, Inc. Speaker's Bureau; Self; Gilead Sciences, Inc.
1259-P: Adherence and Persistence for Dulaglutide (DU) vs. Basal Insulin (BI) in Injection-Naïve Patients with Type 2 Diabetes (T2D): The DISPELTM Study
Authors: MODY REEMA , HUANG QING , YU MARIA , WANG LIYA , ZHANG XIAN , GRABNER MICHAEL , PATEL HIREN
Published: June 2019

Adherence and persistence are key considerations in patient-centric treatment selection for T2D management. The objective of this retrospective real-world study was to assess 1-year adherence and persistence using different measures among injection naïve patients with T2D initiating DU vs. BI. A U.S. claims database was used to identify patients with T2D initiating DU or BI between Nov’14 - Apr’17 (index date=earliest fill date). Patients ≥18 years, with no claim for any antidiabetic injectable in the 6 months pre-index period (baseline), continuous enrollment and ≥1 HbA1c result at baseline and 1-year post-index were included. Two widely used measures for assessing persistence of injectables in the real-world were implemented. DU users were propensity-matched 1:1 to BI users. Matched cohorts (903 pairs) were balanced in baseline patient characteristics with mean age of 54 years. Key study outcomes are included in the Table. Using the 45-day gap measure, more BI vs. DU patients discontinued their therapy but more BI patients restarted their index therapy. More DU vs. BI patients discontinued based on the 90th percentile measure, and more DU patients restarted their index therapy. In this real-world study, DU demonstrated higher adherence than BI. Given the results, the most appropriate persistence measure may vary for different classes of antidiabetic injectables.

Disclosure

R. Mody: Employee; Self; Eli Lilly and Company. Q. Huang: None. M. Yu: Employee; Self; Eli Lilly and Company. Employee; Spouse/Partner; Lifelabs. Stock/Shareholder; Self; Eli Lilly and Company. L. Wang: Employee; Self; HealthCore. Employee; Spouse/Partner; Janssen Pharmaceuticals, Inc. X. Zhang: None. M. Grabner: None. H. Patel: Employee; Self; Eli Lilly and Company. Stock/Shareholder; Self; Eli Lilly and Company.

Funding

Eli Lilly and Company
1261-P: Assessing Data Availability and Benchmarking Performance of Quality Measures for the T1D Exchange Quality Improvement Collaborative
Authors: CABRERA ALYSSA B. , ALONSO GUY T. , CORATHERS SARAH , LEE JOYCE M. , PRAHALAD PRIYA , RIOLES NICOLE
Published: June 2019

The T1D Exchange QI Collaborative was formed in 2016 to accelerate quality improvement (QI) at clinics serving people with type 1 diabetes (T1D).

Through an evidence-based review and idealized design process, the collaborative chose seven process and outcome measures to be the focus of improvement activities directed at high-risk T1D patients (2 or more A1c values >9% in the preceding year) aged 12-26 years. We report monthly aggregate statistics from seven Collaborative clinics for the measures and show the statistics for May and August 2018.

A substantial percent of patients meet high risk criteria across all centers, and there is wide variation in performance measures. No center has the capacity to report on all measures, but there are incremental improvements in data availability. Outcomes remain suboptimal, particularly in this high-risk population. These measures will be continuously tracked to define network progress and to design QI interventions to improve glycemic outcomes. The work of the Collaborative and the creation of a technology platform will improve reporting capacity and drive QI activities.

Disclosure

A.B. Cabrera: None. G.T. Alonso: None. S. Corathers: None. J.M. Lee: Consultant; Self; Taiho Oncology, Inc. P. Prahalad: None. N. Rioles: None.

Funding

The Leona M. and Harry B. Helmsley Charitable Trust
1267-P: Psychometric Development of a Multidimensional Patient-Reported Outcomes Questionnaire and Clinical Dialogue Platform for Routine Diabetes Care
Authors: SKOVLUND SOREN E. , NØRGAARD LISE MELLERGAARD , STEFANSEN SIMON , DE LICHTENBERG TRINE HONNENS , TROELSEN LISE , PIETRASZEK ANNA , KJÆR PERNILLE H. , LARSEN HANNE RAVN , JAKOBSEN POUL ERIK O. , EJSKJAER NIELS
Published: June 2019

Aim: To develop a multi-dimensional Patient Reported Outcomes (PRO) questionnaire to improve person-centered care for type 1 and 2 diabetes across sectors in Denmark.

Methodology: A stepwise cross-regional multi-stakeholder multi-disciplinary co-development process was undertaken: 1) Patient-important PRO domains for value based diabetes care defined (ADA 2018), 2) Multi-sector strategy for active use of PRO to benefit People With Diabetes (PWD) and care quality 3) Conceptual measurement model and psychometric methodological foundation, 4) Literature review and mapping of PRO items/scales 5) Iterative item selection/testing and design of PRO dialogue tool 7) Qualitative, clinical and psychometric evaluation.

Results: The final e-PRO questionnaire (53-78 items) consisted of pre-existing/adapted items (from e.g., WHO-5, PROMIS-10, MDI, DSC-R) and newly developed global essence domain and single items covering: General health, social support, life stress, psychological well-being, symptom distress (neuropathic pain, heart, gastro-intestinal, sexual, sleep, fatigue, foot problems), diabetes well-being, worries, limitations and support, self-care, lifestyle and technology confidence, wishes for support, confidence in care access, medicine burden and satisfaction, blood sugar regulation (stability, moderate/severe hypoglycemia), preferred topics for next visit. Workshops and selective item testing (n=85) supported item acceptability and content coverage. A novel web dialogue tool with algorithms/resources to enable PWD and providers to interpret and follow-up on each PRO output was designed as part of the project.

Conclusions: A systematic collaborative process led to a new PRO questionnaire and dialogue tool for use in routine diabetes care. Research is now ongoing to validate scoring and evaluate benefits of real-world use of intervention for PWD, clinicians and payers.

Disclosure

S.E. Skovlund: Stock/Shareholder; Self; Novo Nordisk A/S. L. Nørgaard: None. S. Stefansen: None. T. Honnens de Lichtenberg: None. L. Troelsen: None. A. Pietraszek: None. P.H. Kjær: None. H. Ravn Larsen: None. P.O. Jakobsen: None. N. Ejskjaer: None.

Funding

Danish Health Care System
1288-P: The Association between CDSS Use and Diabetes Management
Authors: DAVLYATOV GANISHER , BAIDWAN NAVNEET KAUR , MEHTA TAPAN
Published: June 2019

Research Objective: Healthcare providers’ decision-making can be aided by a computerized decision support system (CDSS) that might include alerts for drug allergies, checks for drug-drug interactions, and reminders for preventive screening tests. Over 30 million Americans suffer from diabetes. Diabetes prevalence and management success rates vary based on the patient’s age, gender, race, socioeconomic status, and location. The effectiveness of CDSS on overall patient outcomes haven’t been fully evaluated. This project aims to test the association between CDSS use and diabetic patients’ blood glucose level.

Study Design: We used FQHC annual report for the period 2014-2017. The outcome variable was the percentage of patients 18-75 years of age with diabetes who had hemoglobin (HbA1c) less than 8.0 percent during the measurement period. The independent variable was the use of CDSS. The study controlled for organizational and patient characteristics. To uncover the average effect of a covariance over the entire sample, generalized estimating equations model with state and year fixed effects was utilized.

Principal Findings: The use of CDSS at FQHCs was associated with 6.2 percent improvement in diabetic control (p=0.037). Moreover, 1 percent increase in patients with Medicare coverage was significantly associated with better diabetic control (0.36, p<0.001). Likewise, an increase in patients with private insurance was associated with better diabetic control (0.13, p=0.003). Asian and Hispanics, compared to whites, were more likely to maintain their blood glucose at adequate levels (0.26, p<0.001, and 0.07, p=0.008, respectively).

Conclusions: Study suggests the use of CDSS may lead to better health outcomes for patients with diabetes at FQHC. The findings of this study can help tailor treatment to vulnerable populations, inform funding agencies with respect to policies to incentivize and encourage FQHCs to adopt and use CDSS. Further, FQHC administrators can gain insight to make informed decisions to invest in CDSS.

Disclosure

G. Davlyatov: None. N. Baidwan: None. T. Mehta: None.
129-LB: Similar Efficacy, Safety, and Immunogenicity in People with Diabetes Using SAR341402 or Insulin Aspart: Gemelli 1 Study
Authors: GARG SATISH K. , WERNICKE-PANTEN KARIN , WARDECKI MAREK , KRAMER DANIEL , DELALANDE FRANCOIS , SHAH VIRAL N. , FRANEK EDWARD , SADEHARJU KARITA , MONCHAMP TRAVIS
Published: June 2019

SAR341402 (SAR-Asp) was developed as a biosimilar/follow-on product to rapid-acting insulin NovoLog®/NovoRapid® (NN-Asp).

This 6-month randomized, controlled, open-label, phase 3 study compared efficacy and safety of SAR-Asp and NN-Asp in adults with type 1 diabetes (T1D) or type 2 diabetes (T2D) also using insulin glargine (GLA100) as basal insulin. In total 597 adults with diabetes were randomized (1:1; 497 with T1D, 100 with T2D) to a multiple daily injection regimen of SAR-Asp or NN-Asp along with using once daily GLA100. Glucose targets levels were <180 mg/dL (2h-postprandial) and 80-130 mg/dL (fasting and pre-prandial) while avoiding hypoglycemia. Primary endpoint was HbA1c change (non-inferiority margin of 0.3%) from baseline to week 26 (tested for non-inferiority of SAR-Asp vs. NN-Asp). Immunogenicity was assessed by anti-insulin aspart antibody (AIA) status (positive/negative) and titers during the study.

SAR-Asp was non-inferior to NN-Asp for change in HbA1c, with similar insulin dosages. There was no difference in the percentage of patients reporting hypoglycaemia. Immunogenicity and safety profiles (adverse events, hypersensitivity events and injection site reactions) were similar for SAR-Asp and NN-Asp (Table).

We conclude that biosimilar/follow-on SAR-Asp is safe, effective and well-tolerated as insulin aspart in adults with T1D or T2D.

Disclosure

S.K. Garg: Advisory Panel; Self; Eli Lilly and Company, Roche Pharma, Sanofi-Aventis, Zealand Pharma A/S. Research Support; Self; Eli Lilly and Company, WebMD. K. Wernicke-Panten: Employee; Self; Sanofi-Aventis Deutschland GmbH. M. Wardecki: Employee; Self; Sanofi Research & Development. Stock/Shareholder; Self; Sanofi. D. Kramer: Employee; Self; Sanofi-Aventis Deutschland GmbH. Stock/Shareholder; Self; Sanofi-Aventis Deutschland GmbH. F. Delalande: None. V.N. Shah: Advisory Panel; Self; Sanofi US. Consultant; Self; Dexcom, Inc. E. Franek: Advisory Panel; Self; Boehringer Ingelheim International GmbH, Novartis AG, Novo Nordisk Inc. Speaker’s Bureau; Self; AstraZeneca, Bioton, Boehringer Ingelheim International GmbH, Medtronic, Novartis AG, Novo Nordisk Inc., Polfa Tarchomin S.A. K. Sadeharju: Research Support; Self; AstraZeneca, Bayer AG, ICON plc., Sanofi. T. Monchamp: Research Support; Self; Amarin Corporation, Novo Nordisk Inc., Sanofi, TrialNet.

Funding

Sanofi