bluuebunny/crossref_metadata_2025 huggingface dataset:
722-P: Tirzepatide Improves Multiple Aspects of Beta-Cell Function
Authors: MARI ANDREA , LI JING , URVA SHWETA , HEISE TIM , DE VRIES J. HANS , PRATT EDWARD J. , HEINE ROBERT J. , THOMAS MELISSA K. , MILICEVIC ZVONKO , MATHER KIEREN J.
Published: May 2022

We investigated the effect of tirzepatide (TZP) 15 mg (novel GIP-GLP-1 dual receptor agonist) , placebo and semaglutide 1 mg (SEMA) on beta-cell function using euglycaemic and hyperglycemic glucose clamps (EGC, HGC) and Mixed Meal Tolerance Tests (MMTT) in a 28-week double-blind randomized controlled trial of people with type 2 diabetes. During EGC and HGC, TZP improved insulin sensitivity (M-value) , first and second phase insulin secretion (ISR) and beta-cell glucose sensitivity (ratio of ISR and glucose increments) more than SEMA and placebo (Table; EASD symposium 2021) . During MMTT, both fasting and AUC glucose were reduced more with TZP than with SEMA or placebo, while incremental glucose AUC was reduced with TZP and SEMA vs. placebo similarly. Despite similarly reduced incremental glucose AUC, insulin AUC and incremental insulin AUC were reduced by TZP but not by SEMA. Model-derived beta-cell glucose sensitivity was increased with TZP and SEMA from baseline similarly. In contrast, ISR at 7.2 mmol/L glucose increased more with TZP than with placebo and SEMA (Table) . The glucose-lowering effect of TZP is mediated through improvements in multiple aspects of beta-cell function, including beta-cell glucose sensitivity and ISR, and in insulin sensitivity, resulting in pronounced lowering of fasting and postprandial glucose. These effects help explain the superior improvement in glucose control seen with TZP vs. comparators in clinical trials.

Disclosure

A. Mari: Consultant; Lilly. Research Support; Lilly. J. Li: Employee; Eli Lilly and Company. Stock/Shareholder; Eli Lilly and Company. S. Urva: Employee; Eli Lilly and Company. T. Heise: Advisory Panel; Novo Nordisk A/S. Research Support; ADOCIA, AstraZeneca, Biocon, Boehringer Ingelheim International GmbH, Crinetics Pharmaceuticals, Inc., Eli Lilly and Company, Gan & Lee Pharmaceuticals, Genova, Nestlé, Neuraly Inc., Novo Nordisk A/S, Sanofi, Zealand Pharma A/S. Speaker's Bureau; Eli Lilly and Company, Gan & Lee Pharmaceuticals, Novo Nordisk A/S. J. De Vries: Advisory Panel; ADOCIA, Novo Nordisk A/S, Zealand Pharma A/S. Speaker's Bureau; Novo Nordisk A/S. E.J. Pratt: Employee; Eli Lilly and Company. R.J. Heine: Employee; Eli Lilly and Company. M.K. Thomas: Employee; Eli Lilly and Company. Stock/Shareholder; Eli Lilly and Company. Z. Milicevic: Employee; Eli Lilly and Company. K.J. Mather: Employee; Eli Lilly and Company. Stock/Shareholder; Eli Lilly and Company.

Funding

Eli Lilly and Company
725-P: Protein Biomarkers Associated with Dulaglutide and Cardiovascular Events in REWIND
Authors: WILSON JONATHAN M. , PARE GUILLAUME , LEE SHUN FU , COLHOUN HELEN M. , QIAN HUI-RONG , PIRRO VALENTINA , HOOVER ANASTASIA , LAKSHMANAN MARK , RUOTOLO GIACOMO , DUFFIN KEVIN L. , GERSTEIN HERTZEL C.
Published: May 2022

In the REWIND trial, dulaglutide (DU) reduced the risk of CV outcomes compared with placebo (PL) (Major Adverse Cardiovascular Event [MACE]-3 hazard ratio 0.88) . This post hoc analysis studied circulating protein biomarkers associated with CV events to better understand how DU reduces CV risk.

Patients ≥50 years of age with T2D, A1C ≤9.5%, BMI ≥23 kg/m2, and CV risk were treated DU (1.5 mg weekly) or PL. This case/control study matched 9 cases with MACE with 9 non-MACE controls. A total of protein biomarkers were measured by immunoassay in plasma and serum. Biomarkers associated with DU were first identified by fitting the natural log (ln) of biomarker changes from baseline to 2 years of treatment to an ANCOVA model; the p value cutoff was 0.0026 after Bonferroni correction. Then, the identified biomarkers were fit to a logistic regression model for MACE case/control to test possible impact on CV outcome.

Four biomarkers were associated with DU: C-reactive protein (hsCRP) , N-terminal prohormone of brain natriuretic peptide (NT-proBNP) , and Growth/Differentiation Factor-15 (GDF-15) had attenuated increases over 2 years for DU vs. PL, and C-peptide had a greater increase over 2 years for DU vs. PL. Logistic regression analyses showed that patients with smaller increases in hsCRP, NT-proBNP, and GDF-15 were less likely to have MACE. C-peptide levels did not significantly impact MACE occurrence.

Disclosure

J.M.Wilson: Employee; Eli Lilly and Company. K.L.Duffin: Employee; Eli Lilly and Company, Stock/Shareholder; Eli Lilly and Company, Pfizer Inc. H.C.Gerstein: Advisory Panel; Abbott, Eli Lilly and Company, Hanmi Pharm. Co., Ltd., Novo Nordisk, Pfizer Inc., Sanofi, Viatris Inc., Consultant; Kowa Company, Ltd., Other Relationship; DKSH, Eli Lilly and Company, Sanofi, Zuellig Pharma Holdings Pte. Ltd., Research Support; AstraZeneca, Eli Lilly and Company, Merck & Co., Inc., Novo Nordisk, Sanofi. G.Pare: Advisory Panel; Amgen Inc., Bayer AG, Sanofi, Research Support; Bayer AG. S.Lee: None. H.M.Colhoun: Advisory Panel; Bayer AG, Eli Lilly and Company, Novo Nordisk, Consultant; AstraZeneca, Research Support; AstraZeneca, Stock/Shareholder; Bayer AG, Roche Pharmaceuticals. H.Qian: Employee; Eli Lilly and Company, Stock/Shareholder; Apple, Eli Lilly and Company. V.Pirro: Employee; Eli Lilly and Company, Stock/Shareholder; Eli Lilly and Company. A.Hoover: Employee; Eli Lilly and Company. M.Lakshmanan: Employee; Eli Lilly and Company, Stock/Shareholder; Eli Lilly and Company. G.Ruotolo: None.

Funding

Eli Lilly and Company
73-OR: Loss of NADPH Oxidase–Derived Superoxide Impairs Autoreactive T Cell Trafficking into Islets to Delay Type 1 Diabetes Development
Authors: BLUM SAMUEL I. , BARRA JESSIE , BAKER ROCKY L. , TSE HUBERT M.
Published: May 2022

Type 1 diabetes (T1D) and β-cell destruction is mediated by proinflammatory cytokines, reactive oxygen species (ROS) , and immune cells. NADPH oxidase (NOX) -derived superoxide, a precursor for many ROS, regulate cell signaling, cellular differentiation, survival, and autoimmune responses in T1D. We previously discovered that NOX-derived superoxide promote chemokine synthesis and skew macrophages and T cells towards a proinflammatory response in T1D. Yet, it remains unknown if NOX is necessary for diabetogenic T cell trafficking into islets. Using non-obese diabetic (NOD) mice lacking NOX-derived superoxide (NOD.Ncf1m1J ) , we tested the hypothesis that loss of NOX-derived superoxide delays T1D by impairing autoreactive T infiltration into islets. Female NOD.Ncf1m1J mice (n=20) had a significant delay in spontaneous T1D development, as only 20% became diabetic by 40-weeks of age compared to 90% NOD mice (n=23) . Flow cytometry analysis of 12-week-old NOD.Ncf1m1J mice revealed a significant reduction in pancreatic CD4 T cells expressing CD69+ (5.5-fold) , CCR2+ (1.9-fold) and CCR5+ (2.1-fold) compared to NOD. NOD.Ncf1m1J islets also had significantly fewer total CD4+ T cells (1.8-fold) , CD25+ CD4+ T cells (2.0-fold) , naïve CD4+ T cells (2.0-fold) , and effector CD4+ T cells (2.2-fold) compared to NOD. Utilizing tetramer staining to identify autoreactive T cells, we observed a significant reduction in NOD.Ncf1m1J islet-infiltrating CD4+ T cells specific for insulin (Ins) (2.6-fold) , Ins-chromogranin A hybrid peptide (HIP) (3.0-fold) , and Ins-islet amyloid polypeptide HIP (2.6-fold) compared to NOD. Our findings provide evidence that loss of NOX-derived superoxide can impair autoreactive T cell activation and islet-infiltration as a possible mechanism to delay T1D development. Future studies will determine if NOX regulates islet chemokine synthesis to mediate autoreactive T infiltration into islets.

Disclosure

S.I.Blum: None. J.Barra: None. R.L.Baker: None. H.M.Tse: None.

Funding

Translational and Molecular Sciences T32 (GM109780) , Immunologic Diseases and Basic Immunology T32 (AI007051) , National Institutes of Health NIDDK F31 (DK130551) , National Institutes of Health NIDDK R (DK126456) , National Institutes of Health NIDDK RO1 (DK127497) .
733-P: Initiation of iGlarLixi vs. Basal-Bolus Insulin (BB) in Adults with Type 2 Diabetes (T2D) Advancing from Basal Insulin (BI) Therapy: The SoliComplex Real-World Study
Authors: PANTALONE KEVIN M. , HELLER CAROLINE , LAJARA ROSEMARIE , LEW ELISHEVA , LI XUAN , DEX TERRY A. , KILPATRICK RACHEL
Published: May 2022

Aim: When T2D is suboptimally controlled with BI, 1-3 daily injections of prandial insulin are commonly added (BB regimen) . Once daily iGlarLixi is an alternative treatment. This analysis evaluated the use of iGlarLixi vs. BB on T2D outcomes.

Methods: This retrospective analysis of the US Optum Clinformatics database compared outcomes in adults (≥18 y) with T2D who previously received BI and newly initiated iGlarLixi or BB between Jan 1, 2017, and Jun 30, 2020. Persistence (primary endpoint) , adherence, healthcare resource utilization (HRU) , costs, any hypoglycemia, and HbA1c change were assessed at 12 months.

Results: Propensity score matching generated cohorts (n=1070 each) that were well balanced with similar mean ± SD age (iGlarLixi: 63.9 ± 11.0 y; BB: 64.5 ± 11.3 y) , HbA1c (iGlarLixi: 9.2 ± 1.7%; BB: 9.2 ± 1.8%) , oral agent use, BI use, and HRU. The primary endpoint was met with treatment persistence being statistically significantly higher for iGlarLixi vs. BB at 12 months. Adherence was numerically higher for iGlarLixi, and hypoglycemia rates, HRU and costs, numerically lower. HbA1c reduction was similar between groups (Table) .

Conclusions: In this observational study, initiation of once daily iGlarLixi vs. BB insulin was associated with higher persistence and similar HbA1c reduction without increasing HRU or costs.

Disclosure

K.M. Pantalone: Consultant; AstraZeneca, Bayer AG, Corcept Therapeutics, Diasome, Eli Lilly and Company, Merck & Co., Inc., Novo Nordisk, Sanofi. Research Support; Bayer AG, Merck & Co., Inc., Novo Nordisk. Speaker's Bureau; AstraZeneca, Corcept Therapeutics, Merck & Co., Inc., Novo Nordisk. C. Heller: Consultant; Sanofi. Employee; Aetion. R. Lajara: None. E. Lew: Employee; Sanofi. X. Li: Employee; Eisai Co., Ltd., Sanofi. T.A. Dex: Employee; Sanofi. Stock/Shareholder; Pfizer Inc., Teva Pharmaceutical Industries Ltd., Viatris Inc. R. Kilpatrick: Speaker's Bureau; Abbott Diabetes, Amgen Inc., Novo Nordisk, Sanofi.

Funding

Sanofi
734-P: The Effect of Adjunctive Therapy with Liraglutide on Insulin Sensitivity in Overweight Persons with Type 1 Diabetes
Authors: DEJGAARD THOMAS F. , FRANDSEN CHRISTIAN S. , JOHANSEN NICKLAS , MADSBAD STEN , KNOP FILIP K. , ANDERSEN HENRIK U.
Published: May 2022

Type 1 diabetes is associated with an almost threefold higher mortality rate than the general population, primarily driven by excess mortality from cardiovascular disease. Insulin sensitivity evaluated by the estimated glucose disposal rate (eGDR) is a recognized predictor of cardiovascular disease. Here, we evaluated the effect of adjunctive therapy with the glucagon-like peptide 1 receptor agonist (GLP-1RA) liraglutide on eGDR in patients with type 1 diabetes. We calculated eGDR post-hoc in a randomized (1:1) , placebo-controlled, double-blind, clinical trial (NCT01612468) that evaluated the effect of liraglutide 1.8 mg once daily (uptitrated via 0.6 mg and 1.2 mg over 2 weeks) as add-on to insulin treatment compared with placebo in 100 overweight persons with type 1 diabetes (35/65 women/men, age 48 (12) years (mean (standard deviation)) , diabetes duration 23 (12) years, BMI 30 (3) kg/m2, glycated hemoglobin A1c 8.7 (0.7) % / 72 (8) mmol/mol) . After 12 weeks of treatment, liraglutide significantly increased eGDR compared with placebo. However, at end of treatment at week 26, the between-group difference was not statistically significant (Table 1) . These data indicate that liraglutide may improve eGDR, a recognized predictor of cardiovascular disease, in overweight persons with long-standing type 1 diabetes and inadequate glycemic control.

Disclosure

T.F.Dejgaard: Advisory Panel; Novo Nordisk, Research Support; Novo Nordisk, Speaker's Bureau; AstraZeneca, Boehringer Ingelheim International GmbH, Novo Nordisk. C.S.Frandsen: None. N.Johansen: Employee; Novo Nordisk A/S. S.Madsbad: None. F.K.Knop: Advisory Panel; Boehringer Ingelheim International GmbH, Eli Lilly and Company, Merck Sharp & Dohme Corp., Novo Nordisk, Sanofi, ShouTi, Zucara Therapeutics, Consultant; AstraZeneca, Eli Lilly and Company, Novo Nordisk, Pharmacosmos A/S, Sanofi, ShouTi, Zealand Pharma A/S, Zucara Therapeutics, Research Support; AstraZeneca, Novo Nordisk, Sanofi, Zealand Pharma A/S, Speaker's Bureau; AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Novo Nordisk, Sanofi, Stock/Shareholder; Antag Therapeutics. H.U.Andersen: Advisory Panel; Abbott Diabetes, Stock/Shareholder; Novo Nordisk A/S.

Funding

Supported by an unrestricted grant by Novo Nordisk
735-P: Direct Anti-Inflammatory and Antifibrotic Effects of a Novel Long-Acting Glucagon/GIP/GLP-1 Triple Agonist, HM15211, in Thioacetamide-Induced Mouse Model of Liver Injury and Fibrosis
Authors: KIM JUNG KUK , LEE JONG SUK , KIM YOHAN , LEE SEON MYEONG , KWON HYUNJOO , PARK EUNJIN , CHOI JAEHYUK , BAE SUNGMIN , KIM DAEJIN , LEE SANG HYUN , CHOI IN YOUNG
Published: May 2022

HM152 is a novel long-acting triple agonist consisting of Glucagon/GIP/GLP-1 triple agonist conjugated to human IgG FC fragment via short PEG linker. Previously, therapeutic benefits of HM152 were demonstrated in diet-induced animal models of NASH and fibrosis. Here, direct anti-inflammatory and -fibrotic effects of HM152 were further evaluated in TAA (thioacetamide) -induced liver injury and fibrosis mouse, and investigate underlying mechanism. To induce liver injury and fibrosis, gradually increased dose of TAA was injected to mouse for 12 weeks, and HM152 was administered during last weeks. Interestingly, HM152 treatment significantly reduced hepatic hydroxyproline (-51% vs. Veh, p<0.01) , Sirius red positive area (-65% vs. Veh, p<0.001) , and fibrosis score (0.7 for HM152 vs. 3.0 for Veh, p<0.001) . Considering baseline fibrosis score at week 2 (1.0) , HM152 could confer both potential reversal effect on pre-existing fibrosis and prevention effect on fibrogenesis. Consistently, expression of hepatic marker genes for fibrosis (i.e. collagen-1α1) and inflammation (i.e. F4/80, TNF-α) were significantly reduced in HM152 group. Furthermore, multiplex cytokine analysis revealed that HM152 treatment was associated with robust reduction across pro-inflammatory cytokines including TNF-α, IL-1β, and IL-6. Significant reduction in blood level of liver enzymes was also confirmed. Mechanistically, PMA/LPS-induced pro-inflammatory cytokine secretion of THP-1 cell was significantly attenuated by HM15211. TGF-β-induced collagen production was also reduced in LX2 cell.

In conclusion, HM152 markedly improved liver inflammation and fibrosis in TAA mice, and related mechanism was elaborated by in vitro studies. Thus, HM152 could be a novel therapeutic option for fibrosis due to NASH. Human study is ongoing to assess the clinical relevance of these findings.

Disclosure

J.Kim: None. S.Lee: n/a. I.Choi: None. J.Lee: None. Y.Kim: None. S.Lee: None. H.Kwon: Employee; Hanmi Pharm. Co., Ltd. E.Park: Employee; Hanmi Pharm. Co., Ltd. J.Choi: Employee; Hanmi Pharm. Co., Ltd. S.Bae: None. D.Kim: None.
74-OR: Adoptively Transferred T Lymphocytes with Reduced iPLA2b Expression Delays Type 1 Diabetes Development in NOD Mice
Authors: WHITE TAYLEUR , CHALFANT CHARLES , DILORENZO TERESA P. , RAMANADHAM SASANKA , STEPHENSON DANIEL
Published: May 2022

Type 1 diabetes (T1D) is a T-cell mediated autoimmune disease characterized by the destruction of insulin-producing pancreatic islet β-cells. An understudied area is the role lipid signaling plays in this process. We find that the Ca2+-independent phospholipase A2β (iPLA2β) is induced under a diabetic milieu and mitigation of iPLA2β activity attenuates β-cell death. iPLA2β, a member of the PLA2 family, hydrolyzes the sn-2 substituent from glycerophospholipid substrates to yield a free fatty acid. When the fatty acid is arachidonic acid, it can be metabolized to eicosanoids, many of which are pro-inflammatory. To address our overarching hypothesis that iPLA2β-derived lipids (iDLs) contribute to T1D development, we investigated the role of immune cell-iDLs by utilizing a T-cell adoptive transfer. We isolated CD4+/8+ T-cells from splenocytes prepared from 11-week-old donor female NOD and NOD.iPLA2 β +/- (HET) . These were transferred i.p. to 4-week-old NOD.scid recipient mice. We find that NOD4/8-recipient mice develop T1D between 14-16 weeks of age. In contrast, T1D onset in HET4/8-recipient mice is delayed by 12 weeks and this was associated with better glucose tolerance, compared to NOD4/8 T-cell recipients. This finding is also supported by histology analysis of the pancreatic islet, which revealed less islet infiltration, more islet abundance, and the frequency of CD4 T cells were increased in the pancreas of HET4/8-recipient mice compared to NOD4/8 recipients. Further, lipidomics analyses revealed that HET donor T-cell production of proinflammatory lipids (i.e., PGE2 and DHETs) is decreased, relative to NOD T-cells. These findings suggest that pro-inflammatory iDLs generated by CD4 T-cells are critical contributors T1D development and can be targeted to counter T1D onset.

Disclosure

T.White: None. C.Chalfant: None. T.P.Dilorenzo: None. S.Ramanadham: None. D.Stephenson: None.

Funding

Training Program in Cell, Molecular, and Developmental Biology (5T32GM008111-34) NIH/NIDDK (R01DK110292) NIH/NIAID R21 (AI 146743) Cell, Developmental, & Integrative Biology (CDIB) , the University of Alabama at Birmingham
741-P: Real-World Weight-Loss Effectiveness of GLP-1 Agonists among Patients with Type 2 Diabetes: A Retrospective Cohort Study
Authors: LUO JING , SHU INGRID , KORYTKOWSKI MARY T. , ROMETO DAVID A. , ARNOLD JONATHAN , WHITE GRETCHEN E.
Published: May 2022

The real-world weight loss effectiveness of GLP-1RAs have not been well described. We conducted a cohort study using EHR data from an integrated healthcare system based in PA. Non-pregnant adults first dispensed a GLP-1RA between 20 and 2018 were eligible. We excluded those without: 1) at least 72 weeks of continuous enrollment after the first dispense date,2) at least 1 year of baseline enrollment data, and3) at least one valid weight measurement within the 8 wks before the dispense date and at least one weight measure during follow-up. We used descriptive statistics to report percent change in body weight from baseline in each 8 wk follow-up interval ending in +72 wks. We used linear mixed models with a person-level random intercept controlling for variables associated with missing weight data to estimate percent body weight change during follow-up. Our cohort included 2,398 patients (mean[SD] age 48.4[10.3], 53% female) , with a BMI[SD] of 37[7.5] and a mean baseline weight of 238[54] lbs. In the final 8 wk interval of follow-up (64-72 wks) , the modeled mean percent weight change was -2.5% (95% CI: -2.8 to -2.1) . An estimated 29.9% (95% CI: 27.2 to 32.6) of patients lost at least 5% body weight at this time. In this real-world study using data from ∼2,400 patients with overweight or obese and type 2 diabetes, starting a GLP-1RA was associated with a modest amount of weight loss through 72 weeks.

Disclosure

J.Luo: None. I.Shu: None. M.T.Korytkowski: None. D.A.Rometo: Advisory Panel; Nestlé Health Science. J.Arnold: None. G.E.White: None.

Funding

NIDDK (K23ADK120956)
748-P: Clinically Relevant Predictors of Cardiovascular Events in Patients with Type 2 Diabetes Mellitus: A Pooled Analysis from Clinical Studies
Authors: MALHOTRA ANKUR , BADER GIOVANNI
Published: May 2022

Patients with type 2 diabetes mellitus (T2DM) are at greater risk of developing cardiovascular disease (CVD) . We aimed to explore the association between several baseline parameters and risk of cardiovascular (CV) events in patients with T2DM and whether evidence from clinical data at T2DM onset could be useful in identifying patients at risk of subsequent CV events. Data for baseline visits were extracted from 34 globally conducted clinical studies. Framingham risk equation was used to assess the CV risk at baseline. In the overall pooled population (n=18,076) , 2130 (13.6%) patients had CVD history at baseline. The mean (SD) age of the patients was 56.8 (10.7) years, total cholesterol was 196.4 (41.0) mg/dL, low-density lipoprotein (LDL) was 115.4 (36.8) mg/dL, systolic blood pressure (SBP) was 132.7 (14.6) mmHg with disease duration of 5. (5.10) years and Framingham risk score (FRS) of 20.71 (12.68) . An incremental risk for subsequent CV events was observed in patients having none or multiple risk factors. Patients having CVD history and FRS ≥20% were significantly associated with a higher risk of CV events (HR [95% CI]: 7.8 [5.0, 12.3]; p<0.001; Figure) . Overall, these analyses suggests that clinical data collected at the onset and follow-up of T2DM such as CVD history, high LDL and SBP may help in identifying patients who are at high risk of subsequent CV events.

Disclosure

A.Malhotra:Employee; Novartis India . G.Bader:Employee; Novartis AG.

Funding

Novartis Pharma AG
750-P: Novel Approach for Development of Oral GLP-1 Receptor Agonist with Superior Bioavailability and Antidiabetic Efficacy
Authors: JI PARK EUN , JEON OK-CHEOL , PARK JONG-SUNG , CHOI JIYOUNG , SHIN JAEHEE , LIM SUNGMOOK , PARK SOOBONG , LEE SEULKI
Published: May 2022

While glucagon-like peptide 1 receptor agonists (GLP-1 RAs) are highly effective at lowering HbA1c, currently available GLP-1 RA delivery options are suboptimal; SC administrations hinder patient adherence and oral administrations have lower bioavailability due to enzymatic instability and insufficient gastrointestinal absorption. A novel approach to deliver GLP-1 RAs with superior bioavailability and better patient adherence would further improve the antidiabetes efficacy of GLP-1 RAs. Hence, this study assesses an oral formulation facilitating intestinal absorption of DD02S, a new GLP-1RA. Biological activities, gastrointestinal stabilities and Caco-2 permeability study of DD02S were performed in vitro. The in vivo efficacy of the oral formulation was evaluated by intraduodenal injection in rats. DD02S was formulated as enteric coated tablets and orally administered in dogs. Pharmacological efficacy was demonstrated by repeated dosing in db/db mice. DD02S was designed to introduce a ligand and fatty acid to facilitate cellular uptake via intestinal transporters, increase enzyme stability, and enable reversible plasma protein binding without loss of potency. The oral formulation enhanced the intestinal stability as well as permeation via trans and paracellular routes. The increased intestinal absorption was confirmed by intraduodenal injection in rats. Following the oral administration of the enteric coated tablets to dogs, the mean bioavailability ranged from 5.0-10.1% with variability of 78-117% and pharmacokinetic parameters were suitable for once daily oral dosing. In the antidiabetes efficacy study of DD02S, significant reduction of HbA1c was observed in a dose-dependent manner. This study demonstrates the potential antidiabetes efficacy of DD02S with once daily oral dosing. Our novel approach for oral delivery is promising to development of other oral peptide therapeutics.

Disclosure

E.Park: Employee; D&D Pharmatech. O.Jeon: Employee; D&D Pharmatech. J.Park: Employee; D&D Pharmatech. J.Choi: Employee; D&D Pharmatech. J.Shin: Employee; D&D Pharmatech. S.Lim: Board Member; D&D pharmatech. S.Park: Board Member; D&D Pharmatech. S.Lee: Board Member; D&D Pharmatech.
754-P: Antifibrotic Potential of a Novel Long-Acting Glucagon/GIP/GLP-1 Triple Agonist (HM15211) in Preclinical Models of IPF
Authors: LEE SEON MYEONG , KIM JEONG A. , LEE JONG SUK , KIM JUNG KUK , BAN YOUNG-HWAN , LEE JONGSOO , BAE SUNGMIN , KIM DAEJIN , LEE SANG HYUN , CHOI IN YOUNG
Published: May 2022

Idiopathic pulmonary fibrosis (IPF) is an irreversible and progressive pulmonary disorder in which scarring of lung tissue eventually leads to death. A large of studies have demonstrated that the core mechanisms in fibrosis across various organs are similar. Previously, excellent preclinical efficacy of HM15211, a novel long-acting Glucagon/GIP/GLP-1 triple agonist, on liver fibrosis was confirmed (the major distribution tissues of HM152were liver and lung) . These findings prompted us to hypothesize that HM152might be also a promising drug candidate for IPF. Its effect on pulmonary function and mortality was evaluated in bleomycin (BLM) -induced mouse model of lung fibrosis. BLM was instilled intratracheally to assess the therapeutic benefits of HM152over pirfenidone (PIRF) and nintedanib (NINT) (FDA-approved drugs for IPF) . Briefly, HM152was administered 7 days post BLM instillation, and then saturation of peripheral oxygen (SpO2) and survival rate were monitored until day 14 and day 21, respectively. 1.5 U/kg BLM mice showed markedly impaired lung function at day 7 as indicated by SpO2 (84.0 vs. 95.6% for normal) , which was further exacerbated until day 14 (77.1% vs. 96.0% for normal) . Interestingly, while PIRF (81.9%) and NINT (81.3%) prevent additional lung function impairment without any reversal effects, HM152treatment significantly restored impaired lung function (91.5%) at day 14. In addition, at 21 days after 2.5 U/kg BLM treatment, substantial decline in survival rate (17%) was effectively inhibited by HM15211, NINT, and PIRF. Notably, HM152 (61%) showed more improved survival rate than NINT (33%) , and PIRF (28%) , suggesting potential superiority of HM152over current IPF drugs.

In conclusion, HM152may be a novel therapeutic potential for pulmonary fibrosis over current standard of care for IPF. Further evidences from the mechanistic studies will shed light on a direct inhibitory effect of HM152on pulmonary fibrosis.

Disclosure

S.Lee: None. I.Choi: None. J.A.Kim: None. J.Lee: None. J.Kim: None. Y.Ban: None. J.Lee: None. S.Bae: None. D.Kim: None. S.Lee: n/a.
755-P: Liraglutide plus Basal Insulin Combination Therapy in Japanese Old-Aged People with Type 2 Diabetes: Peak Age at 70s
Authors: KASHIMA KOJI , SHIMIZU HIROYUKI , YAMADA MASANOBU
Published: May 2022

Objective: In management type 2 diabetes (T2D) , it is required to pursue the A1C <7% Target avoiding hypoglycemia, especially in increased old aged population in Japan. We examined the effectiveness of liraglutide (Lira) and insulin degludec (IDeg) combination therapy in 134 Japanese persons with T2D.

Methods: Hospitalized persons who started this combination therapy since year 2014 were recruited. Changes of HbA1c and basal Insulin doses were evaluated for 4.5 years after discharge. Glycemic variability (GV) was evaluated by ADRR in person who did SMBG. Since preserved β-cell function might influence the management, effectiveness was also compared by duration of T2D ≤ 5-year (SHORT; n=53) or > 5-year (LONG; n=81) . Persons in SHORT were with shorter duration of T2D than LONG (0.67±1.5 vs. 18.7±9.3 years: p<0.0001) , higher C-peptide Index (1.50±0.76 vs. 0.97±0.66: p<0.001) .

Results: 1) Mean HbA1c in total had maintained ≤7.1% from 3rd to 54th month. But mean HbA1C in SHORT was remarkably improved, and had maintained ≤6.6% from 3th until 54th month with extremely lower ADRR score ∼5. 2) At hospitalization, maximum IDeg dose was 15.5±9.2 (6∼46) (SHORT) vs. 14.0±7.6 (4∼40) U/day (LONG) , because of higher HbA1C (12.3±2.3% vs. 10.3±2.4%: p<0.0001) at the baseline. But insulin requirement rapidly decreased in SHORT. On titration, IDeg was titrated not to reach BG <80mg/dL. IDeg could be quitted in ∼75% vs.∼15% at 24th month, respectively. On 3rd month in insulin user, IDeg dose decreased to 7.5±4.1U/day vs. 9.6±5.6U/day, despite lower Lira dose in SHORT with 0.66±0.15mg/day vs. in LONG 0.72±0.23mg/day. 3) Distribution of peak age in total was 70s, and the CKD rate was the more pronounced at 57% (25/44) . Although SHORT group were younger (60.8±11.7 vs. 70.8±11.0 years old: p<0.01) , they already had CKD in 32.1%.

Conclusion: Lira based therapy is useful for attaining HbA1c Target with simple insulin titration, longer durability, and for pursuing reno-protection in whole generation with CKD.

Disclosure

K.Kashima: None. H.Shimizu: None. M.Yamada: None.
756-P: The Effect of Semaglutide on Alanine Aminotransferase (ALT) Levels: Results from the Association of British Clinical Diabetologists (ABCD) Audit
Authors: CRABTREE THOMAS S.J. , SENNIK DEVESH K. , BICKERTON ALEX , BARNES DENNIS , SIVAPPRIYAN SIVA , ADAMSON KAREN , PHILLIPS SUZANNE M. , EVANS ALISON , LARSEN NIELS , PANESAR AVINASH , CULL MELISSA L. , GALLEN IAN W. , IDRIS ISKANDAR R. , RYDER ROBERT E.
Published: May 2022

Obesity and type 2 diabetes are important drivers for the development of nonalcoholic fatty liver disease (NAFLD) . Glucagon-like peptide-1 receptor agonists (GLP1RAs) are efficacious for these conditions, but their potential as treatments for NAFLD remains unclear. As serum ALT concentration is routinely measured in clinical care, we evaluated the impact of the GLP1RA, semaglutide, on ALT in those at risk of NAFLD.

Methods: Data submitted to the ABCD semaglutide audit (launched in 2019) were analysed. Change in ALT from baseline was assessed and corrected for change in covariates and concomitant medications using a multiple linear regression in Stata 16 . Baseline ALT levels were used to perform a stratified analysis as follows: normal (ALT 0-29U/L) , mildly elevated (30-59 U/L) and significantly elevated (≥60U/L) . Missing data were multiply imputed.

Results: Data for 1,623 individuals (50.2% men) were included with baseline (mean±SD) : age 58.9±11.0 years, HbA1c9.4±1.7%, weight 104.6±2.8kg, BMI 37.1±7.4kg/m2 and median (IQR) diabetes duration 10.9 years (6-15.4) and ALT 26U/L (19-36) . Median (IQR) follow-up was 8.2 months (5-12) . At follow-up, changes in HbA1c and weight were -1.2% (95%CI -1.0, -1.3; p<0.001) and -2.4kg (95%CI -1.7, -3.1; p<0.001) respectively. No significant change in ALT was seen across the entire cohort (p=0.172) . However, ALT rose in the normal group (+14.6U/L; 95%CI 10.4, 18.8; p<0.001) and fell in the significantly elevated group (-16.2U/L; 95%CI -11.8, -20.5; p<0.001) . No change was noted in the mildly elevated group (p=0.33) . The differences between groups were statistically significant (p<0.0001) .

Conclusion: Among patients with significantly raised ALT, semaglutide was associated with ALT reduction, but this finding may result from regression to the mean. Measurement in parallel of further biomarkers of liver fibrosis will be required to assess the potential of semaglutide as a NAFLD therapy.

Disclosure

T.S.J. Crabtree: Other Relationship; Abbott Diabetes, Novo Nordisk, Sanofi. D.K. Sennik: Speaker's Bureau; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Novo Nordisk, Sanofi. D. Barnes: None. S. Sivappriyan: None. K. Adamson: None. S.M. Phillips: None. A. Evans: None. N. Larsen: None. A. Panesar: None. I.W. Gallen: None. I.R. Idris: None. R.E. Ryder: None.

Funding

The ABCD audit is support by an unrestricted grant from NovoNordisk
757-P: Perioperative Fully Closed-Loop vs. Standard Insulin Therapy in Adults Undergoing Pancreatic Surgery
Authors: HERZIG DAVID , SUHNER SIMON , CECCHINI LUCA , ROOS JONATHAN L. , SCHÜRCH DANIEL , NAKAS CHRISTOS , BELDI GUIDO , GLOOR BEAT , WILINSKA MALGORZATA E. , HOVORKA ROMAN , VOGT ANDREAS , BALLY LIA
Published: May 2022

Background and Aims: Pancreatic surgery challenges perioperative glucose management by abrupt changes in endogenous insulin stores, surgical stress, medication and nutritional support. We hypothesize that fully closed-loop (CL) insulin delivery, compared to usual care, may better accomodate the complex needs of this population.

Methods: In this subpopulation analysis of a randomized controlled trial (NCT04361799) we compared the CamAPS HX fully CL system using subcutaneous faster insulin aspart (CL) with standard insulin treatment (control) in patients undergoing pancreatic surgery. Glucose control was assessed using the Dexcom G6 continuous glucose monitoring (blinded in the control group) from hospital admission to discharge (max 20 days) .

Results: Twelve patients (6 per group, 58% female, mean±SD age 69±18 years, BMI 27.3±3.9 kg/m2, HbA1C 7.8±2.0 %, 66 % total pancreatectomy) were analyzed. Median [IQR] %time in target glucose range (5.6-10.0mmol/L) was 76.5 [75.3; 80.3] % with CL vs. 45.6 [24.1; 55.5] % with control (P=0.005) . Time in hypoglycemia (<3.9mM and <3.0mM) did not differ between groups (P=0.81 and P=0.46) . No study-related serious adverse events occurred in either group.

Conclusions: Perioperative fully CL in patients undergoing partial or total pancreatectomy improves glucose control compared to standard insulin therapy without a higher risk of hypoglycemia.

Disclosure

D.Herzig: None. R.Hovorka: Advisory Panel; Eli Lilly and Company, Other Relationship; CamDiab Ltd., Research Support; Abbott Diabetes, Dexcom, Inc., Medtronic, Speaker's Bureau; Dexcom, Inc., Eli Lilly and Company, Novo Nordisk. A.Vogt: None. L.Bally: None. S.Suhner: None. L.Cecchini: None. J.L.Roos: None. D.Schürch: None. C.Nakas: None. G.Beldi: None. B.Gloor: None. M.E.Wilinska: Consultant; CamDiab Ltd.

Funding

Swiss Helmut Horten Foundation;Swiss Foundation for Anaesthesiology and Intensive Care;Product support by Dexcom Inc.;
768-P: Clinical Outcomes of Euglycemic DKA with a Computerized Insulin Algorithm: Descriptive Analysis of a Nationwide Cohort
Authors: MESSLER JORDAN , VELLANKI PRIYATHAMA , BOOTH ROBERT
Published: May 2022

Euglycemic DKA (euDKA) is an underdiagnosed endocrine emergency and may not be treated appropriately treated due to lower than expected glucose levels. EuDKA has been increasing in prevalence due to the use of SGLT2-inhibitors. Glycemic or insulin outcomes for hospitalized patients with euDKA have been limited to case reports and series and have not been reported in a large cohort. Individual-level data were extracted from the Glytec Inpatient Database from 154 hospitals across the United States from (2017-2021) . All patients were on Glucommander IV, a computerized continuous insulin infusion (CII) algorithm, for at least 1 hour, to examine glycemic outcomes and insulinometrics. EuDKA was defined as patients with age ≥18 years with a BG < 250 mg/dl and who met the following criteria on admission: bicarbonate <18 mmol/L, pH <7.3, with ketones present in serum or urine. All patients had an ICD of Eor Eor A1c >6.5%. We identified 533 patients with euDKA (Table) . Time to HCO3 > 18 mEq/L was 14.1 hours. The incidence of hypoglycemia was low. Analysis of a nationwide cohort shows that euDKA can be safely and effectively treated with a computerized algorithm in the hospital, as patients achieved rapid time to target, resolution of DKA, and low mortality.

Disclosure

J.Messler: Employee; Glytec, LLC. P.Vellanki: n/a. R.Booth: Employee; Glytec, LLC.
773-P: Impact of Six Months of Hybrid Closed-Loop Use on Sleep in Youth with Type 1 Diabetes and Their Parents
Authors: COBRY ERIN C. , KARAMI ANGELA J. , VIGERS TIMOTHY B. , PYLE LAURA , JOST EMILY , MELTZER LISA J. , WADWA R. PAUL
Published: May 2022

Many youth with T1D and their parents do not achieve sufficient sleep duration or quality. While HCL use improves nocturnal glycemic control, it is unclear whether sleep duration and quality are impacted. The objective of this study was to measure sleep outcomes in children with T1D and parents after HCL initiation.

Youth with T1D starting the Tandem Control-IQ (CIQ) and a parent enrolled in an observational study. Actigraphy data (sleep duration, sleep efficiency, and wake after sleep onset (WASO)) and sleep surveys (Pittsburgh Sleep Quality Index (PSQI) , PROMIS Pediatric Sleep Disturbance and Sleep-Related Impairment) were collected at baseline and 3- and 6-months after CIQ initiation.

Thirty-nine youth (11.1±3.6 yrs (range 3-17) , T1D duration 2.5±3.0 yrs, 54% male) and parents (42.5±6.7 yrs, 18% male) participated. Parents significantly improved WASO at 3- and 6-months (p=0.0 and 0.007) and sleep quality at 3-months (p=0.011) . No significant changes in subjective or objective sleep outcomes for children occurred other than a decrease in PROMIS Sleep-Related Impairment parent proxy at 3 months (p=0.041) .

Youth with T1D and their parents experience insufficient sleep duration and poor sleep quality. Parent subjective sleep quality and WASO improved with CIQ use. Improving sleep quality is complex and further research is needed to identify causes of sleep disruptions and intervention methods.

Disclosure

E.C.Cobry: None. A.J.Karami: None. T.B.Vigers: None. L.Pyle: None. E.Jost: Other Relationship; Tandem Diabetes Care, Inc. L.J.Meltzer: None. R.Wadwa: Advisory Panel; Dompé, Consultant; Beta Bionics, Inc., Other Relationship; Tandem Diabetes Care, Inc., Research Support; Dexcom, Inc., Eli Lilly and Company, Tandem Diabetes Care, Inc.

Funding

National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases (K12DK094712)
778-P: Variations in Insulin Pump Use across Pediatric Endocrinology Centers in the U.S.
Authors: MUNGMODE ANN , ADAMS BLAKE V. , DOCTER OLIVIA , FOGEL NAOMI R. , ILKOWITZ JENIECE T. , IZQUIERDO ROBERTO , LEE JOYCE M. , MIYAZAKI BRIAN , NEYMAN ANNA , RECKSON ISABEL , SCHMITT JESSICA , EBEKOZIEN OSAGIE
Published: May 2022

Background: The T1D Exchange Quality Improvement Collaborative (T1DX-QI) is a learning network of over forty US type 1 diabetes clinics. Clinics share best-practice ideas for quality improvement and use data for population health research. This study benchmarks insulin pump use across pediatric clinics in the T1DX-QI.

Method: T1DX-QI clinics report monthly on critical metrics, including the percentage of patients with HbA1c <7% or using a pump, and other quality metrics. Median values for each site were calculated using Lahey P run charts between July 2020 and June 2021. These results are shared non-anonymized internally among participating T1DX-QI clinics.

Results: Across 17 T1DX-QI clinics, the percentage of patients using pumps ranged from 23% to 79% (Figure 1, A; mean and median pump use were 51.5% and 49.0%, respectively) . Clinic-specific average percentage of patients with HbA1c < 7% ranged from 35% to 12% (Figure 1, B) . There were no observed differences in pump use by patient population size.

Conclusion: The T1DX-QI benchmarks key clinical metrics to support quality improvement, share best practices, and promote learning across clinics.

Disclosure

A. Mungmode: None. B.V. Adams: None. O. Docter: None. N.R. Fogel: None. R. Izquierdo: None. J.M. Lee: Advisory Panel; GoodRx. Consultant; Tandem Diabetes Care, Inc. B. Miyazaki: None. A. Neyman: None. I. Reckson: None. J. Schmitt: None. O. Ebekozien: None.

Funding

The Leona M. and Harry B. Helmsley Charitable Trust
78-OR: LRH-1/NR5A2 Agonism Triggers an Anti-Inflammatory Phenotypic Switch of Immune Cells from Patients with Type 1 Diabetes and Improves Islet Engraftment/Function
Authors: COBO-VUILLEUMIER NADIA , RODRIGUEZ-FERNANDEZ SILVIA , LORENZO PETRA I. , LOPEZ LIVIA , DORRONSORO AKAITZ , LACHAUD CHRISTIAN C. , ALMENARA-FUENTES LIDIA , RAMOS-RODRÍGUEZ MIREIA , MERIDA ISABEL , AGUILAR-DIOSDADO MANUEL , NANO RITA , PIEMONTI LORENZO , PASQUALI LORENZO , MARTIN FRANZ , GARCIA-SANCHEZ ISABEL , MARTINEZ-BROCCA MARIA ASUNCION , VIVES-PI MARTA , GAUTHIER BENOIT R.
Published: May 2022

Administration of the LRH-1 agonist BL0refrains hyperglycemia in 3 mouse models of type 1 diabetes (T1DM) . This antidiabetes action correlated with beta cell mass preservation and the presence of anti, rather than pro, inflammatory immune cells, indicating tolerization. Herein, we sought to translate these data to human immune cells of T1DM patients to demonstrate BL0benefits to re-educate the immune system and to assess its therapeutic value on human islet engraftment/function. Blood mononuclear cells purified from blood samples (healthy and T1DM) were derived in culture into 1) pro-inflammatory macrophages (MDM1) , 2) mature dendritic cells (mDCs) , 3) T-cells and 4) B-cells. Cells were then treated with BL0 and processed for 1) cell surface marker profiling, 2) cytokine secretome profiling, 3) T-cell proliferation and 4) RNAseq. In T1DM samples, BL0reduced the expression of pro-inflammatory markers on MDM1 (CD80) and mDCs (CD54 and CXCR4) and the secretion of the pro-inflammatory cytokines, CXCL6 and CCL24 (MDM1) as well as IL7 (mDCs) . Moreover, in these samples, BL0also increased Tregs, but not B-cells. T-cell proliferation was blunted by BL001-treated mDCs and Tregs. RNAseq analysis of BL001-treated MDM1 revealed increased expression of genes encoding components of complex I, III, IV, and V of the respiratory chain consistent with a transition from a glycolytic driven MDM1 to an oxidative phosphorylation driven MDM2 anti-inflammatory phenotype. BL0administration to STZ-treated mice transplanted with human islet improved survival correlating with reduced hyperglycemia, increased circulating human C-peptide, preserved beta cell mass, and reduced CD4+ T-cell infiltration. Our results establish that BL0can induce a pro-to-anti-inflammatory phenotypic switch to human immune cells, and improve human islet engraftment/function, supporting the therapeutic benefits of BL0in human.

Disclosure

N. Cobo-Vuilleumier: None. S. Rodriguez-Fernandez: Employee; Ahead Therapeutics SL. P.I. Lorenzo: None. A. Dorronsoro: None. C.C. Lachaud: None. L. Almenara-Fuentes: Employee; Ahead Therapeutics SL. M. Ramos-Rodríguez: None. I. Merida: None. M. Aguilar-Diosdado: None. L. Piemonti: None. L. Pasquali: None. F. Martin: None. I. Garcia-Sanchez: None. M. Martinez-Brocca: None. M. Vives-Pi: Research Support; Ahead Therapeutics S.L. B.R. Gauthier: None.

Funding

JDRF (2-SRA-2019-837-S-B) Consejeria de Salud y Familia, junta de Andalucia (PI-0001-2020)
788-P: Development of an Extended-Wear Infusion Set with Angled Cannula
Authors: ZHANG GINA , ANSELMO EVAN , ORTIGOZA JESSICA L. , CHATTARAJ SARNATH
Published: May 2022

Objective: Medtronic Mio™ 30 infusion set (M30IS) is a single-use consumable for pump users with pre-loaded inserter, utilizing a 30° insertion angle, and labeled for 3-day use. The M30IS wear duration is impacted by initial local trauma caused by insertion & cannula and sustained inflammation mostly by insulin infusion (especially insulin aggregates and other impurities in the infusate) , with the latter being predominant. Recently, a 7-day Medtronic Extended Infusion Set (MEIS) based on 3-day Mio™ Advance IS with a 90° soft cannula was developed and commercialized in Europe, by improving insulin formulation stability in the fluid path. This study is focused on applying the extended wear (EW) technology from MEIS to the M30IS to develop an EW set with angled cannula (the EM30IS) .

Method: This is a cross over study of M30IS and EM30IS on drug-induced Type 1 diabetic Yucatan pigs. Each animal wore both sets multiple times with one each time on the abdomen that was continuously infused with Novolog™ subcutaneously via a pump for 1-week or until failure. Blood glucose were measured 5 times/day. Physical examination and serum panel tests were conducted for safety evaluation.

Result: Fourteen wears were completed for each device. No significant safety concern was identified. Compared to the 90° cannula sets tested on the same model having occlusion alarm rate of 0∼20% for MEIS and ∼40% for 3-day sets at 7 days, no occlusion alarm was detected in either M30IS or EM30IS. Survival rate of EM30IS (86%, similar to MEIS) trended higher than that of M30IS (71%) . Average total daily dose of insulin increased with time for M30IS (Day 1: 14.4 U, Day 6: 18.1U) , whereas remained nearly unchanged for EM30IS (Day 1: 14.9 U, Day 6: 15.6 U) .

Conclusion: The data indicated that the EM30IS is safe and efficacious on the diabetic porcine model for subcutaneous insulin infusion for 7 days. The EW technology is equally safe and effective on extending the wear duration of M30IS. The EM30IS is moving to the next phase of product development.

Disclosure

G.Zhang: Employee; Medtronic. E.Anselmo: Employee; Medtronic. J.L.Ortigoza: Employee; Medtronic. S.Chattaraj: Employee; Medtronic.
796-P: Perceived Potential Benefits and Barriers for Using a Bionic Invisible Pancreas
Authors: HERMANNS NORBERT , FINKE-GROENE KATHARINA , KULZER BERNHARD , EHRMANN DOMINIC
Published: May 2022

A fully implantable automated insulin delivery system consisting of an intraperitoneal pump and an implantable CGM sensor (Bionic Invisible Pancreas - BIP) is under development. The occurrence of potential benefits or barriers to the use of the BIP was assessed in people with diabetes under different treatment regimens (MDI, CSII, CSII and CGM) . They were asked to provide a rating of 9 potential benefits and potential barriers of BIP on a five-point Likert scale ranging from 1 - strongly disagree - to 5 - strongly agree. Data from 38 people with type 1 diabetes were analysed (MDI: n=12; CSII: n=14; CSII and CGM: n=12) . In general, participants reported more expected benefits than barriers. The main benefits were increased flexibility and better glucose levels. The main expected barriers related to problems in transferring control to BIP and fears about side effects of implantation (e.g. inflammation) . The benefits and barriers were similar in all three groups (p=0.861 and p=0.669 for differences between groups, respectively) . 76.3% of participants reported that they would use BIP. Participants reported more positive than negative expectations related to the BIP device, regardless of previous insulin treatment. In addition to the fear of side effects during implantation, giving control to the BIP device was perceived as challenging. The present work was supported by H2020-FETPROACT Project FORGETDIABETS, n. 951933

Disclosure

N.Hermanns: Advisory Panel; Abbott Diabetes, Research Support; Becton, Dickinson and Company, Roche Diagnostics, Speaker's Bureau; Berlin-Chemie AG, Novo Nordisk, Sanofi. K.Finke-groene: Speaker's Bureau; Berlin-Chemie AG. B.Kulzer: Advisory Panel; Bayer AG, Bayer AG, Becton, Dickinson and Company, Becton, Dickinson and Company, Berlin-Chemie AG, Berlin-Chemie AG, Dexcom, Inc., Dexcom, Inc., Insulet Corporation, Novo Nordisk, Roche Diabetes Care, Sanofi, Sanofi-Aventis Deutschland GmbH, Research Support; Novo Nordisk, Roche Diabetes Care. D.Ehrmann: Advisory Panel; Dexcom, Inc., Consultant; mySugr, Roche Diabetes Care, Speaker's Bureau; Berlin-Chemie AG, Dexcom, Inc.

Funding

The present work was supported by H2020-FETPROACT Project FORGETDIABETS, n. 951933