Scientific Affairs Research Articles

88-LB: Similar Efficacy and Safety of IGlarLixi When Initiated in Patients with Type 2 Diabetes (T2D) with or without Concomitant Sodium-Glucose Cotransporter-2 Inhibitor (SGLT2i) Use in a Randomized Controlled Trial (RCT) and Real-World Setting

iGlarLixi, the once-daily fixed-ratio combination of insulin glargine 100 U/mL and lixisenatide, has been shown to robustly improve glycemic control in adults with T2D. To assess the effects of iGlarLixi with SGLT2i in T2D, we conducted subgroup analyses according to SGLT2i use in the following populations: 1) adults uncontrolled on GLP-1 receptor agonists (GLP-1 RAs) and oral antidiabetic drugs (OADs) switching to iGlarLixi in the 26-week LixiLan-G RCT (NCT02787551) and 2) adults switching to or adding iGlarLixi in a 6-month, retrospective real-world observational study using data from the U.S. Optum-Humedica electronic medical records database. Endpoints included change in HbA1c and hypoglycemia incidence and event rates. Across the studies, there were no major differences in baseline characteristics for those who initiated iGlarLixi while already using SGLT2i (N=346) and those initiating iGlarLixi without background SGLT2i use (N=1285). HbA1c reductions from baseline to week 26 and hypoglycemia incidence and event rates were similar for iGlarLixi regardless of SGLT2i use (Table). In conclusion, evidence from both RCT and real-world clinical settings support the efficacy and safety of iGlarLixi when used in combination with SGLT2i. Disclosure J. Rosenstock: Research Support; Self; AstraZeneca, Bristol-Myers Squibb, Genentech, Inc., GlaxoSmithKline plc., Lexicon Pharmaceuticals, Inc., Oramed Pharmaceuticals, PegBio Co., Ltd., Pfizer Inc., REMD Biotherapeutics. Other Relationship; Self; Applied Therapeutics, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Intarcia Therapeutics, Janssen Pharmaceuticals, Inc., Novo Nordisk Inc., Sanofi. A. Ali: Advisory Panel; Self; Eli Lilly and Company, Napp Pharmaceuticals, Novo Nordisk A/S, Sanofi. Research Support; Self; Eli Lilly and Company, Gelesis. Speaker’s Bureau; Self; Eli Lilly and Company, Novo Nordisk A/S, Sanofi. Stock/Shareholder; Self; Amarin Corporation. J.J. Meier: Speaker’s Bureau; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Merck Sharp & Dohme Corp., Novo Nordisk A/S, Sanofi. F. Giorgino: Advisory Panel; Self; AstraZeneca, Eli Lilly and Company, Novo Nordisk Inc., Roche Diabetes Care, Sanofi. Consultant; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., LifeScan, Inc., MedImmune, Merck Sharp & Dohme Corp., Roche Diabetes Care, Sanofi. Research Support; Self; Eli Lilly and Company, LifeScan, Inc., Takeda Development Centre Europe Ltd. C. Guja: Advisory Panel; Self; AstraZeneca, Sanofi. Speaker’s Bureau; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Novo Nordisk A/S, Sanofi, Servier. M. Prazny: Speaker’s Bureau; Self; Novartis Pharmaceuticals Corporation, Roche Diabetes Care. Other Relationship; Self; Abbott, Boehringer Ingelheim International GmbH, Lilly Diabetes, Medtronic, Novo Nordisk A/S, Sanofi, Teva Pharmaceutical Industries Ltd. R. Lubwama: Employee; Self; Sanofi US. E. Souhami: Employee; Self; Sanofi. Stock/Shareholder; Self; Sanofi. L. Blonde: Advisory Panel; Self; AstraZeneca, Gilead Sciences, Inc. Consultant; Self; Merck & Co., Inc., Novo Nordisk A/S, Sanofi. Research Support; Self; Janssen Scientific Affairs, LLC., Novo Nordisk A/S, Sanofi. Speaker’s Bureau; Self; Janssen Pharmaceuticals, Inc., Sanofi. Funding Sanofi

271-OR: ADA Presidents’ Select Abstract: Effect of Dapagliflozin on the Incidence of Diabetes: A Prespecified Exploratory Analysis from DAPA-HF

In DAPA-HF, the SGLT2 inhibitor (i) dapagliflozin (dapa) reduced worsening heart failure (HF) and cardiovascular death in 4744 patients (pts) with HF and reduced ejection fraction (HFrEF.) Only 45% had type 2 diabetes (T2D) at baseline. We evaluated whether dapa reduced the incidence of diabetes in the 55% of pts without T2D. Pts were randomized to dapa 10 mg or placebo and followed for a median of 18.2 months. New-onset T2D was defined as A1c ≥6.5% measured at 2 consecutive study visits post-randomization or investigator-reported new T2D (with the initiation of a glucose-lowering agent.) The effect of dapa on incident T2D was assessed using a Cox proportional hazards model and confirmed with a Fine and Gray competing risk model to account for mortality. Of the 2605 non-T2D pts at baseline, 157 developed T2D on trial, 150 (95.5%) of whom had prediabetes (A1c 5.7-6.4%) (136 [86.6%] using the more restrictive 6.0-6.4% criterion.) Those with incident T2D had a higher mean baseline A1c (6.2 ±0.3 vs. 5.7 ±0.4%; p<0.001), greater BMI (28.5 ±5.9 vs. 27.1 ±5.7 kg/m2; p=0.003), and lower eGFR (61.5 ±17.4 vs. 68.2 ±19.3 ml/min/1.73 m2; p<0.001) than those who remained nondiabetic. Dapa reduced new-onset diabetes by 32%: placebo 93/1307 (7.1%) vs. dapa 64/1298 (4.9%); HR 0.68 (95% CI, 0.50-0.94; p=0.019) (Cox.) Results were virtually identical using the Fine and Gray model. Diabetes prevention may be another benefit of dapagliflozin. Disclosure S.E. Inzucchi: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Lexicon Pharmaceuticals, Inc., Novo Nordisk A/S, Sanofi. Consultant; Self; Abbott, Merck & Co., Inc., vTv Therapeutics. K. Docherty: Speaker’s Bureau; Self; Eli Lilly and Company. Other Relationship; Self; AstraZeneca. L. Kober: Speaker’s Bureau; Self; AstraZeneca, Novartis AG. Other Relationship; Self; AstraZeneca. M.N. Kosiborod: Consultant; Self; Amarin Corporation, Amgen, Applied Therapeutics, AstraZeneca, Bayer AG, Boehringer Ingelheim Pharmaceuticals, Inc., Eisai Inc., Eli Lilly and Company, GlaxoSmithKline plc., Glytec, Intarcia Therapeutics, Janssen Scientific Affairs, LLC., Merck & Co., Inc., Novartis Pharmaceuticals Corporation, Novo Nordisk Inc., Sanofi US, Vifor Pharma Group. Research Support; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc. F. Martinez: Board Member; Self; AstraZeneca, Novartis Pharmaceuticals Corporation. P. Ponikowski: None. M.S. Sabatine: Consultant; Self; Amgen, AstraZeneca, Bristol-Myers Squibb, CVS Caremark, DalCor Pharmaceuticals, Dyrnamix Inc., Esperion Therapeutics, Inc., IFM Therapeutics, Intarcia Therapeutics, Ionis Pharmaceuticals, Inc., Medicines Company, MedImmune, Merck & Co., Inc. Research Support; Self; Amgen, AstraZeneca, Bayer U.S., Daiichi Sankyo, Eisai Inc., Intarcia Therapeutics, Janssen Research and Development, Medicines Company, MedImmune, Merck & Co., Inc., Novartis AG, Pfizer Inc., Quark Pharmaceuticals. S. Solomon: Consultant; Self; AstraZeneca, Theracos, Inc. Research Support; Self; AstraZeneca, Theracos, Inc. J. Belohlavek: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim International GmbH. M. Böhm: Speaker’s Bureau; Self; Abbott, Amgen, AstraZeneca, Bayer AG, Boehringer Ingelheim Pharmaceuticals, Inc., Bristol-Myers Squibb, Medtronic, Novartis Pharmaceuticals Corporation, Servier, Vifor Pharma Group. C. Chiang: Speaker’s Bureau; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Daiichi Sankyo, Merck Sharp & Dohme Corp., Novartis AG, Pfizer Inc., Sanofi. R.A. de Boer: Speaker’s Bureau; Self; Abbott, AstraZeneca, Novartis AG, Roche Diagnostics France. M. Diez: Other Relationship; Self; AstraZeneca. A. Dukat: None. C.E.A. Ljungman: Advisory Panel; Self; AstraZeneca, Novartis AG, Pfizer Foundation. Stock/Shareholder; Self; AstraZeneca. Other Relationship; Self; AstraZeneca, Novartis AG. S. Verma: Advisory Panel; Self; Amgen, AstraZeneca, Bayer AG, Boehringer Ingelheim (Canada) Ltd., Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Janssen Pharmaceuticals, Inc., Merck & Co., Inc., Novo Nordisk A/S, Sanofi. Research Support; Self; Amgen, AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Bristol-Myers Squibb, Janssen Pharmaceuticals, Inc., Merck & Co., Inc. Other Relationship; Self; AstraZeneca, AstraZeneca, Bayer AG, Boehringer Ingelheim (Canada) Ltd., Boehringer Ingelheim International GmbH, Eli Lilly and Company, Eli Lilly and Company, EOCI Pharmacomm, Janssen Pharmaceuticals, Inc., Merck & Co., Inc., Novartis Pharmaceuticals Canada Inc., Novo Nordisk A/S, Novo Nordisk A/S, Sanofi, Sanofi, Sun Pharmaceuticals, Toronto Knowledge Translation Working Group. D.L. DeMets: Consultant; Self; Actelion Pharmaceuticals US, Inc., AstraZeneca, Boston Scientific, Bristol-Myers Squibb, DalCor Pharmaceuticals, Intercept Pharmaceuticals, Inc., Medtronic. O. Bengtsson: Employee; Self; AstraZeneca. A. Langkilde: Employee; Self; AstraZeneca. Stock/Shareholder; Self; AstraZeneca. M. Sjöstrand: Employee; Self; AstraZeneca. P. Jhund: Advisory Panel; Self; Cytokinetics Inc. Research Support; Self; Boehringer Ingelheim International GmbH. Speaker’s Bureau; Self; Novartis AG. Other Relationship; Self; AstraZeneca. J.J. McMurray: Other Relationship; Self; AbbVie Inc., Alnylam Pharmaceuticals, Amgen, AstraZeneca, Bayer Healthcare Pharmaceuticals Inc., Bristol-Myers Squibb, Cardurion, GlaxoSmithKline plc., Novartis Pharmaceuticals Corporation, Theracos, Inc. Funding AstraZeneca

1779-P: Liraglutide + Metformin Delays Worsening of Glycemia in Adults with Impaired Glucose Tolerance (IGT) or Type 2 Diabetes (T2D)

The Restoring Insulin Secretion (RISE) Study examined the effect of medications to preserve β-cell function in 267 adults with IGT or drug-naïve, recently diagnosed T2D. Participants were randomized to receive 12 months of blinded metformin (MET) or placebo, 12 months of liraglutide (LIRA)+MET, or 3 months of glargine followed by 9 months of MET, all followed by 9 months off treatment. We examined glycemic worsening, defined as progression from IGT to diabetes by fasting or 2-h glucose on an OGTT at baseline, 6, 12, 15 and 21 months or a rise in quarterly HbA1c to ≥7%s. Time-to-worsening was evaluated across treatment groups using a modified product-limit life-table distribution with a log-rank test. Compared to the other treatments, LIRA+MET had less glycemic worsening at 12 months (on treatment) and 21 months (9 months off treatment); each p<0.01. After stopping treatment, group differences persisted but all groups showed similar rates of glycemic progression (Figure). Using logistic regression, independent predictors of worsening glycemia by months 12 and 21 were treatment with LIRA+MET (p=0.01; p=0.03) and baseline 2-h glucose (p=0.02; p=0.03). Overall, despite similar rates of glycemic worsening after discontinuation of therapy, the sustained on-treatment interval of normoglycemia resulted in less glycemic worsening in LIRA+MET compared with the other RISE interventions. Disclosure S. Sam: None. S. Edelstein: None. K. Utzschneider: Other Relationship; Self; Medtronic. T.S. Hannon: None. E. Barengolts: None. A. Xiang: None. D.A. Ehrmann: None. K.J. Mather: Research Support; Self; Abbott, Merck & Co., Inc., Novo Nordisk Inc., Sanofi. S.E. Kahn: Advisory Panel; Self; Boehringer Ingelheim International GmbH, Eli Lilly and Company, Intarcia Therapeutics, Janssen Scientific Affairs, LLC., Merck & Co., Inc., Novo Nordisk A/S, Pfizer Inc. T. Consortium: None. Funding American Diabetes Association (1-14-RISE-01 to S.E.K.); National Institute of Diabetes and Digestive and Kidney Diseases

2040-P: Chronic Activation of CREB by Islet Amyloid Increases Star (Steroidogenic Acute Regulatory Protein) Expression in Islets

Star, which we have shown to be produced in beta cells, is responsible for transport of cholesterol into mitochondria for the production of steroids. We previously found that Star is upregulated with islet amyloid deposition and this is associated with mitochondrial dysfunction. In steroidogenic tissues, StAR transcription is acutely regulated by cAMP Regulatory Element Binding protein (CREB). To determine whether upregulation of Star expression by islet amyloid deposition is regulated by CREB activation, we studied the effects of amyloid formation in human islet amyloid polypeptide (hIAPP) transgenic islets in vitro (16.7 mM glucose for 144 hrs) and in vivo (high fat diet; HFD for 6 months). In vitro phosphorylation of CREB (pCREB) and Star expression increased only with amyloid formation (Table; Expt 1a), as did expression of other known CREB target genes (Expt 1b). When islets were cultured with the amyloid inhibitor Congo red (CR; 200 μM), the increase of CREB target genes was abrogated (Expt 2), suggesting chronic activation of CREB is downstream of amyloid deposition. Amyloid deposition in vivo was also associated with upregulation of Star and other CREB target genes (Expt 3). In summary, chronic CREB activation is associated with increased Star expression, suggesting a novel pathway for amyloid-induced mitochondrial dysfunction in beta cells. Disclosure M.F. Hogan: None. N. Esser: None. A.T. Templin: None. J.J. Castillo: None. S. Zraika: Research Support; Self; Novartis Pharmaceuticals Corporation. R.L. Hull: None. S.E. Kahn: Advisory Panel; Self; Boehringer Ingelheim International GmbH, Eli Lilly and Company, Intarcia Therapeutics, Janssen Scientific Affairs, LLC., Merck & Co., Inc., Novo Nordisk A/S, Pfizer Inc. Funding American Diabetes Association (1-18-PDF-174 to M.F.H.); U.S. Department of Veterans Affairs (I01BX001060)

1268-P: Associations between ß-Cell Function and Cognitive Measures following Treatment in Youth with Impaired Glucose Tolerance (IGT) or Recently Diagnosed Type 2 Diabetes (T2D)

In cross-sectional studies, adolescents with T2D show poorer cognition than normoglycemic youth. In the Restoring Insulin Secretion (RISE) Study, we assessed longitudinal relationships between insulin sensitivity, β-cell function and cognition in 72 youth (mean age 14.3±2.0, 10-18 y) with IGT or recently diagnosed T2D, randomized to 12 months of metformin (MET) or 3 months of glargine followed by 9 months of metformin (G/M). Hyperglycemic clamps were used to measure insulin sensitivity and β-cell responses: acute (0-10 min) C-peptide response to glucose, steady-state C-peptide (SSCP) at glucose of 11.1 mmol/L, and arginine-stimulated maximum C-peptide response (ACPRmax) at glucose >25 mmol/L. A cognitive battery (CogStateTM and story recall) assessed 1) reaction time; 2) visual discrimination; 3) attention and working memory; and 4) learning and episodic memory. A composite measure of cognition was constructed by scaling the sum of the four domain scores. Linear regression models were fit to assess relationships between cognition, treatment and β-cell function. Treatment group models were adjusted for baseline cognitive function, HbA1c and fasting glucose. β-cell models were adjusted for baseline cognitive and β-cell function. Cognitive composite scores improved over the 12-month treatment period (p<0.001), with no differences between treatment arms. Greater baseline ACPRmax predicted greater improvement in composite scores over 12 months in the G/M (p<0.05), but not MET group (p=0.61). Change in SSCP over the 12-month treatment was positively associated with increased composite scores in the G/M (p<0.05) but not MET group (p=0.35). Thus, improved cognition over the 12-month treatment with G/M in adolescents with IGT or early T2D may be related to practice effects with repeated testing, to changes in β-cell function or to other impacts of insulin treatment. Disclosure S. Craft: Advisory Panel; Self; vTv Therapeutics. M. Tripputi: None. S. Edelstein: None. M. Espeland: Other Relationship; Self; Boehringer Ingelheim International GmbH, Ironwood Pharmaceuticals. A. Claxton: Employee; Self; Alkermes plc. S.A. Arslanian: Research Support; Self; National Institutes of Health. Other Relationship; Self; AstraZeneca, Eli Lilly and Company, Novo Nordisk Inc. E. Barengolts: None. T.S. Hannon: None. S.E. Kahn: Advisory Panel; Self; Boehringer Ingelheim International GmbH, Eli Lilly and Company, Intarcia Therapeutics, Janssen Scientific Affairs, LLC., Merck & Co., Inc., Novo Nordisk A/S, Pfizer Inc. K.J. Mather: Research Support; Self; Abbott, Merck & Co., Inc., Novo Nordisk Inc., Sanofi. B. Mokhlesi: None. K.J. Nadeau: None. A. Sanderlin: None. K.A. Temple: None. P. Zeitler: Consultant; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Daiichi Sankyo, Eli Lilly and Company, Merck & Co., Inc. T. Consortium: None. Funding American Diabetes Association (1-14-RISE-01 to S.E.K.); National Institute of Diabetes and Digestive and Kidney Diseases

959-P: Indirect Treatment Comparison (ITC) of IGlarLixi vs. IDegLira in Adults Inadequately Controlled by GLP-1 Receptor Agonists (GLP-1RAs)

In people with type 2 diabetes uncontrolled by GLP-1 RAs, fixed-ratio combination (FRC; basal insulin + GLP-1 RA) is a recommended option. A PICO-framework systematic review of RCTs followed by an ITC was performed to compare the efficacy and safety of the FRCs iGlarLixi (insulin glargine 100 U/mL + lixisenatide) and IDegLira (insulin degludec + liraglutide) in this population. A fixed effects model was used on the two eligible RCTs. Outcomes: change from baseline to week 26 in HbA1c, clinic fasting plasma glucose (FPG), self-monitored plasma glucose (SMPG), and body weight; proportion achieving HbA1c <6.5 or <7.0 %; hypoglycemia incidence. Baseline characteristics were similar across studies. Significant mean differences were seen in change in HbA1c and FPG favoring IDegLira, but not pre- or postprandial SMPG (breakfast or daily average) or weight (Table). Similar proportions achieved HbA1c targets. Hypoglycemia comparisons suffered from varying definitions, sulfonylurea (SU) use and eligibility, and few events in the GLP-1 RA arms (incidence: 32% [confirmed ≤3.1 mmol/L, 28% without SU] with IDegLira and 9% or 28% [symptomatic <3.0 or ≤3.9 mmol/L] with iGlarLixi). This ITC shows similar FRC HbA1c glycemic target achievement but suggests divergent differences in other glycemia results and hypoglycemia, likely due to different study design and titration application. Disclosure P. Home: Advisory Panel; Self; Roche Diabetes Care. Consultant; Self; Mundipharma International, Novartis AG, Sanofi. Research Support; Self; GlaxoSmithKline plc., Merck & Co., Inc., Sanofi. Other Relationship; Self; AstraZeneca, Boehringer Ingelheim International GmbH. V.R. Aroda: Consultant; Self; Duke, Novo Nordisk Inc., Sanofi. Employee; Spouse/Partner; Merck & Co., Inc. Research Support; Self; Applied Therapeutics, Fractyl Laboratories, Inc., Novo Nordisk Inc., Sanofi. Other Relationship; Self; IMNE, Medscape. M. Fazeli: None. C. Whittington: Employee; Self; Sanofi US. H. Goswami: None. A. Shaunik: None. M. Pourrahmat: Other Relationship; Self; Sanofi US. L. Blonde: Advisory Panel; Self; AstraZeneca, Gilead Sciences, Inc. Consultant; Self; Merck & Co., Inc., Novo Nordisk A/S, Sanofi. Research Support; Self; Janssen Scientific Affairs, LLC., Novo Nordisk A/S, Sanofi. Speaker’s Bureau; Self; Janssen Pharmaceuticals, Inc., Sanofi. S. Kalra: Advisory Panel; Self; Eli Lilly and Company. Speaker’s Bureau; Self; Novo Nordisk A/S, Sanofi-Aventis. Funding Sanofi

2042-P: Loss of Apoptosis Repressor with Caspase Recruitment Domain Promotes High-Fat Diet Induced Hyperglycemia In Vivo

Apoptosis repressor with caspase recruitment domain (ARC) is an endogenous inhibitor of apoptosis signaling. We previously showed ARC is expressed in β cells and ameliorates amyloid-induced β-cell death in vitro. More recently, we found that wild type (WT) and whole-body ARC knockout (KO) mice on an FVB background fed a normal chow diet exhibit no differences in islet area, β-cell area, or α-cell area at 16 (n=5) or 35 weeks (n=7-8) of age. In the present study, we sought to determine whether ARC plays a role in maintaining glycemia in response to the challenge of high fat diet (HFD, 60% kcal from fat) feeding in vivo. At 12 weeks of age, just prior to starting 24 weeks of HFD, ARC KO mice displayed lower body weight than WT mice (0 wks: 26.2±0.6 vs. 30.6±0.8 g; p<0.01; n=13), and this weight difference persisted throughout the HFD study (24 wks: 44.7±2.5 vs. 51.9±1.0 g; p=0.04, n=4-9). Random plasma glucose (PG) was not different between genotypes prior to HFD feeding. With HFD challenge, PG increased significantly in ARC KO but not WT mice (see Table). This elevation in PG in ARC KO mice was observed after 4 weeks of HFD and remained throughout the study. These data indicate that loss of ARC promotes hyperglycemia in response to HFD feeding in vivo. Whether this hyperglycemia in ARC KO mice arises from impaired β-cell compensation due to reduced β-cell mass or function remains to be determined. Disclosure A.T. Templin: None. C.R. Schmidt: None. M.F. Hogan: None. N. Esser: None. R.N. Kitsis: None. R.L. Hull: None. S. Zraika: Research Support; Self; Novartis Pharmaceuticals Corporation. S.E. Kahn: Advisory Panel; Self; Boehringer Ingelheim International GmbH, Eli Lilly and Company, Intarcia Therapeutics, Janssen Scientific Affairs, LLC., Merck & Co., Inc., Novo Nordisk A/S, Pfizer Inc. Funding U.S. Department of Veterans Affairs (I01-BX001060, IK2-BX004659); National Institutes of Health (P30DK017047)

927-P: Effect of Oral Semaglutide with or without Background SGLT2i in Patients with T2D: Subgroup Analysis of PIONEER 4

Glucagon-like peptide-1 receptor agonists (GLP-1RA) and SGLT2 inhibitors (SGLTi) are widely used to treat type 2 diabetes (T2D) but trial data on their combined use are limited. We report the first data on oral semaglutide in combination with SGLT2i. This was a post-hoc subgroup analysis of the 52-week, double-blind, double-dummy PIONEER 4 trial (NCT02863419), in which patients with T2D uncontrolled on metformin with or without SGLT2i were randomized 2:2:1 to once-daily oral semaglutide 14 mg, subcutaneous (s.c.) liraglutide 1.8 mg or placebo. Glycated hemoglobin (HbA1c) and body weight (BW) data presented are for the trial product estimand (on-trial product without rescue medication). In total, 183 (26%) of 711 patients were receiving SGLT2i treatment at baseline which continued throughout the trial. Subgroups of patients receiving SGLT2i had a lower percentage of females, slightly longer mean T2D duration and higher BW. Changes in HbA1c and BW were similar in patients receiving oral semaglutide or s.c. liraglutide with or without SGLT2i. Occurrence of most gastrointestinal adverse events was similar in patients on GLP-1RA with and without SGLT2i. In conclusion, improvements in HbA1c and BW after one year as well as safety profile were similar in patients on GLP-1RA with or without background SGLT2i. Disclosure R.E. Pratley: Other Relationship; Self; AstraZeneca, Eli Lilly and Company, GlaxoSmithKline plc., Glytec, Janssen Scientific Affairs, LLC., Lexicon Pharmaceuticals, Inc., Ligand Pharmaceuticals Incorporated, Merck & Co., Inc., Novo Nordisk Inc., Sanofi. R. Bauer: Employee; Self; Novo Nordisk A/S. S.E. Inzucchi: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Lexicon Pharmaceuticals, Inc., Novo Nordisk A/S, Sanofi. Consultant; Self; Abbott, Merck & Co., Inc., vTv Therapeutics. K. Khunti: Advisory Panel; Self; Amgen, AstraZeneca, Bayer AG, Berlin-Chemie AG, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Menarini Group, Merck Sharp & Dohme Corp., Napp Pharmaceuticals, Novartis AG, Novo Nordisk A/S, Roche Pharma, Sanofi-Aventis, Servier. Board Member; Self; AstraZeneca, Eli Lilly and Company, Merck Sharp & Dohme Corp., Novo Nordisk A/S, Sanofi-Aventis. Consultant; Self; Amgen, AstraZeneca, Bayer AG, Berlin-Chemie AG, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Menarini Group, Merck Sharp & Dohme Corp., Napp Pharmaceuticals, Novartis AG, Novo Nordisk A/S, Roche Pharma, Sanofi-Aventis, Servier. Research Support; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Merck Sharp & Dohme Corp., Novartis AG, Novo Nordisk A/S, Pfizer Inc., Sanofi-Aventis, Servier. Speaker’s Bureau; Self; Amgen, AstraZeneca, Bayer AG, Berlin-Chemie AG, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Menarini Group, Merck Sharp & Dohme Corp., Napp Pharmaceuticals, Novartis AG, Novo Nordisk A/S, Roche Pharma, Sanofi-Aventis, Servier. E.B. Kreiner: Employee; Self; Novo Nordisk A/S. Stock/Shareholder; Self; Novo Nordisk A/S. P.N. Laursen: Employee; Self; Novo Nordisk A/S. J.J. Meier: Speaker’s Bureau; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Merck Sharp & Dohme Corp., Novo Nordisk A/S, Sanofi. Funding Novo Nordisk A/S

2016-P: Bariatric Surgery May Improve Glucose Control among Patients with Type 1 Diabetes

The prevalence of obesity in patients with type 1 diabetes (T1D) is increasing. Obesity and metabolic syndrome are risk factors which contribute to the development and progression of micro- and macrovascular complications. Several studies have shown the beneficial and durable effect of bariatric surgery in patients with type 2 diabetes, but data in patients with T1D are scarce. We evaluated the impact of bariatric surgery in adult T1D patients enrolled in the T1D Exchange Registry. Clinical characteristics, comorbidities, socioeconomic factors and laboratory data were obtained within 5 years before or after bariatric surgery. A linear mixed model was used to compare glycemic and clinical outcomes before and after surgery controlling for patient characteristics. Overall, data were available for 38 patients of which 34 were female, 31 were white non-Hispanic (2 missing race); age and T1D duration at time of surgery was 43±9 yrs and 22 ± 13 yrs. After bariatric surgery, patients had lower HbA1c (8.7±1.4 before vs. 8.1±1.3% after), BMI (37.3±10.2 vs. 33.0±7.2 kg/m2), and LDL level (88±27 vs. 79±19 mg/dL), but only BMI reached statistical significance (Table). Although limitations include a small number of subjects and lack of information on type of surgery, this is to date the largest sample size. Our results suggest evidence T1D bariatric surgery is associated with improvement in diabetes control, although more research is needed. Disclosure F. Vendrame: None. A. Casu: None. R.E. Pratley: Other Relationship; Self; AstraZeneca, Eli Lilly and Company, GlaxoSmithKline plc., Glytec, Janssen Scientific Affairs, LLC., Lexicon Pharmaceuticals, Inc., Ligand Pharmaceuticals Incorporated, Merck & Co., Inc., Novo Nordisk Inc., Sanofi. P. Calhoun: Stock/Shareholder; Self; Dexcom, Inc. Funding The Leona M. and Harry B. Helmsley Charitable Trust (G-2016PG-T1D053)

1112-P: Does Background T2D Therapy Modify the Benefits of Dapagliflozin in Heart Failure? Analysis of the DAPA-HF Trial

Background: At present, dapagliflozin (dapa) is typically used as a 2nd-line glucose-lowering medication (GLM) in T2D, often added to metformin. In DAPA-HF, dapa improved clinical outcomes vs. placebo in patients (pts) with HF and reduced ejection fraction (HFrEF), with or without T2D. We examined whether these benefits varied by background GLM in the T2D cohort, including in drug naïve pts and in pts not on metformin. Methods: The primary outcome was a composite of worsening HF (hospitalization or urgent visit requiring IV therapy) or cardiovascular death. The effect of dapa vs. placebo was examined using Cox proportional hazards models. Results: Of the 2139 T2D pts, 1596 (75%) were treated with GLM: metformin (48%), insulin (25%), sulfonylurea (21%), DPP-4 inhibitor (14%) and GLP-1 agonist (1%). Drug-naïve pts had a lower A1c (6.9%±1.2 vs. 7.5%±1.6; P<0.001) and shorter T2D duration (median 5.5 vs. 103 months; P<0.001). Those not using metformin had a lower eGFR (61 vs. 66; P<0.001). The effect of dapa on the primary outcome was consistent in the drug-naïve vs. pts receiving GLM (HR 0.86 [95%CI 0.60-1.23] vs. 0.72 [0.58-0.88]; P-interaction=0.39) and across GLM classes, including those using vs. not using metformin (HR 0.67 [0.51-0.88] vs. 0.81 [0.64-1.03]; P-interaction=0.30). Conclusion: In DAPA-HF, dapa improved outcomes irrespective of use/no use of GLM or by type of GLM used in pts with T2D and HFrEF. Disclosure K. Docherty: Speaker’s Bureau; Self; Eli Lilly and Company. Other Relationship; Self; AstraZeneca. S.E. Inzucchi: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Lexicon Pharmaceuticals, Inc., Novo Nordisk A/S, Sanofi. Consultant; Self; Abbott, Merck & Co., Inc., vTv Therapeutics. M.N. Kosiborod: Consultant; Self; Amarin Corporation, Amgen, Applied Therapeutics, AstraZeneca, Bayer AG, Boehringer Ingelheim Pharmaceuticals, Inc., Eisai Inc., Eli Lilly and Company, GlaxoSmithKline plc., Glytec, Intarcia Therapeutics, Janssen Scientific Affairs, LLC., Merck & Co., Inc., Novartis Pharmaceuticals Corporation, Novo Nordisk Inc., Sanofi US, Vifor Pharma Group. Research Support; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc. L. Kober: Speaker’s Bureau; Self; AstraZeneca, Novartis AG. Other Relationship; Self; AstraZeneca. A. Langkilde: Employee; Self; AstraZeneca. Stock/Shareholder; Self; AstraZeneca. F. Martinez: Board Member; Self; AstraZeneca, Novartis Pharmaceuticals Corporation. O. Bengtsson: Employee; Self; AstraZeneca. D.L. DeMets: Consultant; Self; Actelion Pharmaceuticals US, Inc., AstraZeneca, Boston Scientific, Bristol-Myers Squibb, DalCor Pharmaceuticals, Intercept Pharmaceuticals, Inc., Medtronic. M. Sjöstrand: Employee; Self; AstraZeneca. M.S. Sabatine: Consultant; Self; Amgen, AstraZeneca, Bristol-Myers Squibb, CVS Caremark, DalCor Pharmaceuticals, Dyrnamix Inc., Esperion Therapeutics, Inc., IFM Therapeutics, Intarcia Therapeutics, Ionis Pharmaceuticals, Inc., Medicines Company, MedImmune, Merck & Co., Inc. Research Support; Self; Amgen, AstraZeneca, Bayer U.S., Daiichi Sankyo, Eisai Inc., Intarcia Therapeutics, Janssen Research and Development, Medicines Company, MedImmune, Merck & Co., Inc., Novartis AG, Pfizer Inc., Quark Pharmaceuticals. S. Solomon: Consultant; Self; AstraZeneca, Theracos, Inc. Research Support; Self; AstraZeneca, Theracos, Inc. P. Jhund: Advisory Panel; Self; Cytokinetics Inc. Research Support; Self; Boehringer Ingelheim International GmbH. Speaker’s Bureau; Self; Novartis AG. Other Relationship; Self; AstraZeneca. J.J. McMurray: Other Relationship; Self; AbbVie Inc., Alnylam Pharmaceuticals, Amgen, AstraZeneca, Bayer Healthcare Pharmaceuticals Inc., Bristol-Myers Squibb, Cardurion, GlaxoSmithKline plc., Novartis Pharmaceuticals Corporation, Theracos, Inc.

1679-P: Islet Autoimmunity in Adults with Impaired Glucose Tolerance (IGT) and Newly Diagnosed, Treatment-Naïve Type 2 Diabetes (NDX T2D) in the Restoring Insulin Secretion (RISE) Study

In obesity, immune cells establish a systemic inflammatory state associated with development of insulin resistance and T2D. Previous studies have shown that peripheral blood mononuclear cell (PBMC) responses to islet proteins (IPs) in adults with established T2D on glucose-lowering therapies identify those patients with more severe β-cell dysfunction. Moreover, attenuation of PBMC responses to IPs in adults with established T2D improves β-cell function. However, the presence of IP reactive PBMCs, glutamic acid decarboxylase autoantibodies (GADA), and their relationship to insulin sensitivity and β-cell function has never been evaluated in IGT or Ndx T2D. We measured at baseline and after 12 months of RISE medication interventions (12 months with either metformin or liraglutide plus metformin or for 3 months with insulin glargine followed by 9 months of metformin), PBMC responses to IPs, GADA, insulin sensitivity, and β-cell function in 258 RISE participants (mean ± SD) 53.3 ± 9.2 years of age, BMI 35.1 ± 5.4 kg/m2, with IGT (n=180) or Ndx T2D (<12 months duration, n=78). At baseline, IP reactive PBMCs were present in 46% of participants with IGT and 40% of participants with Ndx T2D. However, 97% of IGT and 98% of Ndx T2D were GADA negative. There were no significant relationships between the presence of PBMC reactivity to IPs, GADA positivity and insulin sensitivity or β-cell function. RISE treatments did not alter PBMC responses to IPs, GADA, or the relationship between IP reactive PBMCs or GADA with glycemic responses. In summary, IP reactive PBMCs are present in a large percentage of adults with very early dysglycemia, However, the presence of IP reactive PBMCs did not correlate with insulin sensitivity or early β-cell dysfunction. Further studies are needed to unravel the pathogenesis of IP reactive PBMCs and GADA and their effects on β-cell function during progression of T2D. Disclosure B. Brooks-Worrell: None. A.H. Tjaden: None. S. Edelstein: None. B.M. Palomino: None. K. Utzschneider: Other Relationship; Self; Medtronic. S.A. Arslanian: Research Support; Self; National Institutes of Health. Other Relationship; Self; AstraZeneca, Eli Lilly and Company, Novo Nordisk Inc. K.J. Mather: Research Support; Self; Abbott, Merck & Co., Inc., Novo Nordisk Inc., Sanofi. T.A. Buchanan: None. K.J. Nadeau: None. K.M. Atkinson: None. E. Barengolts: None. S.E. Kahn: Advisory Panel; Self; Boehringer Ingelheim International GmbH, Eli Lilly and Company, Intarcia Therapeutics, Janssen Scientific Affairs, LLC., Merck & Co., Inc., Novo Nordisk A/S, Pfizer Inc. J.P. Palmer: None. Funding National Institutes of Health (R01DK107560)

1429-P: Use of Guideline-Recommended Risk-Reduction Strategies among Patients with Type 2 Diabetes and Established ASCVD: A 1-Year Update from Getting to an Improved Understanding of Low-Density Lipoprotein Cholesterol and Dyslipidemia Management (GOULD)

Due to emerging evidence, recent practice guidelines are emphasizing more aggressive use of effective prevention strategies in high-risk patients with diabetes (DM). We assessed changes in the use of evidence-based therapies among pts with DM from a registry of 5006 U.S. participants (pts) with ASCVD and LDL-C ≥70mg/dL across 120 U.S. centers taking lipid-lowering therapy (LLT). Among 1,622 DM pts with 12-month follow-up, 14% had intensification of LLT since baseline, 7% de-escalated. Median LDL-C at 12 months was 81 mg/dL, an 11% decrease from baseline. Among pts in the LDL-C cohorts, the percentage with LDL-C <70mg/dL increased from baseline through 12 months (Table). Use of statins and high-intensity statins was stable, while ezetimibe increased, and PCSK9i’s were initiated in 3% of pts not on a PCSK9i at enrollment. Use of SGLT2i, GLP-1RA’s, and fish oil did not change. At 12 months, 8% were on all guideline-recommended therapies for optimal risk reduction, similar to 7% at baseline (p for trend=0.1). Although some modest improvements in the use of secondary cardiovascular prevention therapies were observed, the proportion of patients with DM and ASCVD that receive optimal guideline-recommended risk reduction strategies remains very low. Disclosure M.N. Kosiborod: Consultant; Self; Amarin Corporation, Amgen, Applied Therapeutics, AstraZeneca, Bayer AG, Boehringer Ingelheim Pharmaceuticals, Inc., Eisai Inc., Eli Lilly and Company, GlaxoSmithKline plc., Glytec, Intarcia Therapeutics, Janssen Scientific Affairs, LLC., Merck & Co., Inc., Novartis Pharmaceuticals Corporation, Novo Nordisk Inc., Sanofi US, Vifor Pharma Group. Research Support; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc. S.V. Arnold: None. J. Delemos: Consultant; Self; Amgen, Novo Nordisk A/S, Regeneron Pharmaceuticals. R.S. Rosenson: Advisory Panel; Self; Amgen, Medicines Company. Consultant; Self; CVS Caremark. Research Support; Self; Amgen, Medicines Company, Novartis Pharmaceuticals Corporation, Regeneron Pharmaceuticals. Other Relationship; Self; Amgen, Kowa Pharmaceuticals America, Inc., UpToDate. C.M. Ballantyne: Consultant; Self; Abbott, Akcea Therapeutics, Amarin Corporation, Amgen, Arrowhead Pharmaceuticals, Inc., AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Corvidia, Denka-Seiken Co., Ltd., Esperion Therapeutics, Inc., Gilead Sciences, Inc., Janssen Pharmaceuticals, Inc., Matinas BioPharma, Merck & Co., Inc., Novartis Pharmaceuticals Corporation, Novo Nordisk Inc., Regeneron Pharmaceuticals, Roche Diagnostic USA, Sanofi. Research Support; Self; Abbott, Akcea Therapeutics, Amgen, Esperion Therapeutics, Inc., Novartis Pharmaceuticals Corporation, Regeneron Pharmaceuticals, Roche Diagnostic USA. Y. Liu: None. K.E. Mues: Employee; Self; Amgen. Stock/Shareholder; Self; Amgen. S. Alam: Employee; Self; Amgen. D.L. Bhatt: Research Support; Self; Abbott, Afimmune, Amarin Corporation, Amgen, AstraZeneca, Bayer Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Cardax, Chiesi USA, Inc., CSL Behring, Ferring Pharmaceuticals, Fractyl Laboratories, Inc., Idorsia, Ironwood Pharmaceuticals, Ischemix, Lexicon Pharmaceuticals, Inc., Lilly Diabetes, Medtronic, Pfizer Inc., PhaseBio Pharmaceuticals, Inc., PLx Pharma Inc., Regeneron Pharmaceuticals, Roche Pharma, Sanofi-Aventis, Synaptic. C. Cannon: None. Funding Amgen Inc.

1794-P: Successful Standardization of a Hyperglycemic Clamp Method across Multiple Clinical Centers in the Restoring Insulin Secretion (RISE) Study

In RISE, repeated measurements of β-cell function and insulin sensitivity were performed using a standardized hyperglycemic glucose clamp method. After in person training, clamps were performed at seven centers, in youth (Y) and adults (A) with impaired glucose tolerance (IGT) or early type 2 diabetes (T2D). The goal was to achieve and maintain a plasma glucose concentration of 200 mg/dL over 120 minutes using a priming bolus followed by a continuous infusion of 20% dextrose adjusted based on plasma glucose measured every 5 minutes. Guidance for achieving target glycemia was formalized using spreadsheet-based calculations for glucose boluses and infusion rate changes, using participant weight and the delta of glucose from 200 mg/dL. We evaluated the achieved bedside glucose relative to target as well as differences between the guidance and selected infusion rates. We also compared relevant subgroups. Data from 923 clamps performed on 379 participants (up to three clamps each) were examined. Overall mean ± SD plasma glucose 10 minutes after the glucose bolus was 189 ± 18 mg/dL. This was higher in Y vs. A (194 ± 20 vs. 188 ± 18, p<0.01) and higher in T2D vs. IGT (192 ± 18 vs. 188 ± 18, p<0.01). At steady state (100-120 minutes) the achieved glucose was 199 ± 8 mg/dL slightly but significantly higher in T2D vs. IGT (200 ± 7 vs. 198 ± 8, p=0.006) and in Y vs. A (200 ± 8 vs. 198 ± 8, p<0.05). The glucose infusion rate guidance was followed overall, but deviations occurred during the first 10 minutes (rate 11 ± 21 mL/hr higher than guidance). This deviation differed by clinic (p<0.01) and by diabetes status (p<0.01), but not in Y vs. A (p=0.26). Deviations from guidance were otherwise minor (2-4 mL/hr) and equal by subgroups except at T=90 min (A > Y p=0.05, IGT > T2D p<0.01). The RISE hyperglycemic clamp procedure used formalized calculations and guidance to standardize the clamp approach. This approach achieved uniformity in performance of glucose clamps in a multicenter study in both Y and A. Disclosure K.J. Mather: Research Support; Self; Abbott, Merck & Co., Inc., Novo Nordisk Inc., Sanofi. A.H. Tjaden: None. S.A. Arslanian: Research Support; Self; National Institutes of Health. Other Relationship; Self; AstraZeneca, Eli Lilly and Company, Novo Nordisk Inc. K. Utzschneider: Other Relationship; Self; Medtronic. S. Caprio: None. K. Utzschneider: Other Relationship; Self; Medtronic. K.M. Atkinson: None. M. Cree-Green: Advisory Panel; Self; Novo Nordisk Inc. K.J. Nadeau: None. T.A. Buchanan: None. S.E. Kahn: Advisory Panel; Self; Boehringer Ingelheim International GmbH, Eli Lilly and Company, Intarcia Therapeutics, Janssen Scientific Affairs, LLC., Merck & Co., Inc., Novo Nordisk A/S, Pfizer Inc. T. Consortium: None. Funding American Diabetes Association (1-14-RISE-01 to S.E.K.); National Institute of Diabetes and Digestive and Kidney Diseases

60-OR: OGTT Glucose Response Curves (GRC), Insulin Sensitivity (IS), and ß-Cell Function (ßCF) in RISE: Youth–Adult Contrast at Randomization and in Response to Interventions to Preserve ßCF

In adults and youth without diabetes, the shape of the OGTT-GRC [Biphasic (BPh), Monophasic (MPh), Incessant Increase (IIn)], identifies individuals with impairment in IS and βCF, worst in IIn, and least in BPh. Youth in the TODAY Study with IIn OGTT-GRC had higher glycemic failure rates and accelerated decline in βCF. In RISE we examined: 1) the shape of the OGTT-GRC in youth (n=85) vs. adults (n=353) at randomization; 2) the association between OGTT-GRCs and hyperglycemic clamp-measured IS and C-peptide-derived βCF; and 3) the change in OGTT-GRC [improvement: change from IIn to MPh or BPh, or MPh to BPh; deterioration: the opposite; and no change] at month 12 (M12) in each intervention arm [Metformin (M), and Glargine followed by M (G-M)]. At randomization, more youth had a BPh curve than adults (18.8% vs. 8.2%, p=0.022), with no difference in prevalence of MPh (70.6% vs. 77.3%) or IIn (10.6% vs. 14.5%) curves. IS did not differ across OGTT-GRCs in youth or adults. However, irrespective of curve type, youth had lower IS than adults (p<0.05). Across OGTT-GRCs, βCF was lowest in IIn vs. MPh and BPh in youth and adults (p <0.05 for each). However, youth compared with adults had higher βCF in BPh and MPh curves (p<0.005), but not IIn. Following intervention, the change in OGTT-GRC did not differ significantly between youth and adults (improvement: 14.5% vs. 18.0%, worsening 21.0% vs. 17.3%, no change 64.5% vs. 64.6% respectively). Moreover, there was no impact of M or G-M treatment on the change in OGTT-GRC from randomization to M12 in youth and adults. In summary, despite a 2-fold higher prevalence of the most favorable BPh OGTT-GRC in youth at randomization, it did not translate to better response to interventions in youth. Moreover, OGTT-GRCs reveal that the typical β-cell hypersecretion in youth is not present with the IIn GRC, emphasizing the severity of β-cell dysfunction in youth with this least favorable OGTT curve shape. Disclosure S.A. Arslanian: Research Support; Self; National Institutes of Health. Other Relationship; Self; AstraZeneca, Eli Lilly and Company, Novo Nordisk Inc. L. El Ghormli: None. J. Kim: None. T.S. Hannon: None. K.J. Mather: Research Support; Self; Abbott, Merck & Co., Inc., Novo Nordisk Inc., Sanofi. S. Caprio: None. E. Barengolts: None. K.J. Nadeau: None. K. Utzschneider: Other Relationship; Self; Medtronic. S.E. Kahn: Advisory Panel; Self; Boehringer Ingelheim International GmbH, Eli Lilly and Company, Intarcia Therapeutics, Janssen Scientific Affairs, LLC., Merck & Co., Inc., Novo Nordisk A/S, Pfizer Inc. T. Consortium: None. Funding American Diabetes Association (1-14-RISE-01 to S.E.K.); National Institute of Diabetes and Digestive and Kidney Diseases

Use of Chloroquine and Hydroxychloroquine in COVID-19 and Cardiovascular Implications: Understanding Safety Discrepancies to Improve Interpretation and Design of Clinical Trials.

Author(s): Oren, Ohad; Yang, Eric H; Gluckman, Ty J; Michos, Erin D; Blumenthal, Roger S; Gersh, Bernard J

Radium-223 (Rad) and niraparib (Nira) treatment (tx) in castrate-resistant prostate cancer (CRPC) patients (pts) with and without prior chemotherapy (chemo).

5540 Background: Despite multimodality txs such as surgery, radiotherapy, hormonal tx and chemo, metastatic CRPC (mCRPC) prognosis remains poor. Research suggests PARP-1 is a key regulator of androgen receptor (AR) signaling and transition to lethal CRPC. Nira is a safe, potent and selective PARP-1/2 inhibitor that has shown single agent clinical activity in CRPC, and Rad is an alpha particle emitter. Addition of PARP inhibition may further enhance the clinical benefit of Rad. Nira has a favorable safety profile however, data on safety, tolerability and efficacy of Nira plus radiotherapy is limited. We hypothesize that targeting the PARP-1/AR axis in combination with radiation is safe and will improve mCRPC management. Methods: This is a phase (ph) Ib dose finding study (NCT03076203) of pts with progressive mCRPC using Time-to-Event Continual Reassessment Method (TITE-CRM). The primary objective is to determine the optimum ph II dose of Nira plus Rad (55 kBq/kg of body weight) in pts with and without prior chemo. Secondary endpoints include PSA reduction at 12 weeks (wks) and radiographic progression-free survival at 6 months. Pts enrolled to one of three dose levels of Nira (100, 200, and 300 mg PO daily). After completing 6 cycles of Rad, pts continued on Nira alone until objective progression, tx intolerance or pt decision. TITE-CRM identifies the maximum tolerated dose (MTD) based on toxicities observed over 12 wks of tx. Results: Between Oct 2017 and Jan 2020, 30 pts were enrolled (15 per stratum). Median age was 70 years; ECOG performance status was 0. The MTD of Nira was 100 mg in the chemo-exposed arm and 200 mg in the chemo-naïve arm. 19 Grade ≥ 3 adverse events were possibly related to tx: lymphocyte count decrease (n = 4, 13%), neutrophil count decrease (n = 3, 10%), anemia (n = 3, 10%), hypertension (n = 3, 10%), platelet count decrease (n = 2, 7%), creatinine increase (n = 1, 3%), hydronephrosis (n = 1, 3%), nausea (n = 1, 3%), white blood cell count decrease (n = 1, 3%). Tx duration and PSA response are shown in the table. Conclusions: Nira plus Rad was determined to be safe and tolerable. The MTD of Nira was identified and is pending ph II investigation. Managed by: Prostate Cancer Clinical Trials Consortium; Funded by: Janssen Scientific Affairs and Bayer Healthcare Pharmaceuticals, Inc Clinical trial information: NCT03076203 . [Table: see text]

Special Section: Memorial Festschrift for the Late Professor Frank Kreith Sunrise Delayed but the Sun Shines Brightly: The Energy-Sustainability Quandary and Legacy of Professor Frank Kreith

Special Section: Memorial Festschrift for the Late Professor Frank Kreith Sunrise Delayed but the Sun Shines Brightly: The Energy-Sustainability Quandary and Legacy of Professor Frank Kreith

Enteral and Parenteral Order Writing Survey—A Collaborative Evaluation Between the Academy of Nutrition and Dietetics’ Dietitians in Nutrition Support Dietetics Practice Group and the American Society for Parenteral and Enteral Nutrition (ASPEN) Dietetics Practice Section

IntroductionIn 2014 and 2017, the Centers for Medicare and Medicaid Services authorized nutrition-related ordering privileges for registered dietitian nutritionists (RDNs) in hospital and long-term care settings, respectively. Despite this practice advancement, information describing current parenteral nutrition (PN) and enteral nutrition (EN) ordering practices is lacking. Dietitians in Nutrition Support, a dietetic practice group of the Academy of Nutrition and Dietetics and the Dietetics Practice Section of the American Society of Parenteral and Enteral Nutrition (ASPEN) utilized a survey to describe PN and EN ordering practices among RDNs in the United States. MethodsA cross-sectional study design was utilized to describe RDN PN and EN ordering privileges. Respondents were asked to describe PN and EN ordering privileges, primary practice setting, primary patient population served, nutrition specialty certification, highest degree earned, career length, and, if applicable, the nature of prior denials for ordering privileges or reasons for not applying for ordering privileges. ResultsSeven hundred two RDNs completed the survey (12% response rate), with 664 RDNs providing complete data. The majority of respondents (n=558) cared for adult/geriatric patients. Among this subset, 47% had no PN ordering privileges; 14% could order and sign PN; 28% could order PN with provider cosignature; and 10% could order partial PN with provider cosignature. Nineteen percent of RDNs had no EN ordering privileges; 37% could order and sign EN; and 44% could order EN with provider cosignature. RDNs with ordering privileges were more likely to have a nutrition specialty certification and work in an academic or community hospital setting. ConclusionPN and EN ordering privileges are varied because of institution and state requirements. Future research describing the outcomes associated with RDN ordering privileges is needed. This article has been approved by the Academy’s Research, International, and Scientific Affairs team and Council on Research and the ASPEN Board of Directors. This article has been co-published with permission in Nutrition in Clinical Practice. The articles are identical except for minor stylistic and spelling differences in keeping with each journal's style. Either citation can be used when citing this article.

Drug Information Association (DIA) Europe - 32nd Annual Meeting, Virtual (June 29-July 3, 2020).

The Drug Information Association (DIA) Europe 2020 brought together multiple stakeholders from around the world including regulatory agencies, industry, patients and academia, to discuss the most innovative topics in healthcare. Main subjects covered were regulatory science, data and data standards, clinical safety and pharmacovigilance, translational medicines and science, patient engagement in clinical development, value and access, medical affairs and scientific communication, health policy, and public affairs and legal issues. The meeting, which was initially intended to take place in Brussels, was finally held virtually due to the COVID-19 situation. This report covers some of the sessions held on these 5 days of state-of-the-art topic discussions.

Awards for Distinguished Scientific Early Career Contributions to Psychology.

The Early Career Awards, given for the first time in 1974, recognize the large number of excellent early career psychologists. Recipients of this award may not have held a doctoral degree for more than nine years. For purposes of this award, psychology has been divided into 10 areas: animal learning and behavior, comparative; developmental; health; cognition/human learning; psychopathology; behavioral and cognitive neuroscience; perception/motor performance; social; applied research; and individual differences. Five areas are considered each year, with areas rotated in two-year cycles. The areas considered in 2019 were animal learning and behavior, comparative; cognition and human learning; developmental psychology; health psychology; and psychopathology. Each year, panels are selected for the areas under consideration, and these panels recommend nominees to the Committee on Scientific Awards. The 2019 recipients of the APA Scientific Contribution Awards were recognized by the 2018 Board of Scientific Affairs and selected by the 2018 Committee on Scientific Awards. (PsycINFO Database Record (c) 2019 APA, all rights reserved).