Bayer HealthCare Pharmaceuticals Research Articles

101-OR: Efficacy and Safety of Once-Weekly Semaglutide 2.0 vs. 1.0 mg for Type 2 Diabetes: SUSTAIN FORTE Randomized Trial

Once-weekly (OW) subcutaneous semaglutide 0.5 and 1.0 mg are approved maintenance doses for type 2 diabetes (T2D) treatment. We hypothesized that a higher dose of 2.0 mg would provide additional glycemic control with more patients achieving treatment targets vs. 1.0 mg. SUSTAIN FORTE (NCT03989232) was a randomized, double-blind, phase 3b trial investigating the efficacy and safety of OW semaglutide 2.0 vs. 1.0 mg after 40 weeks of treatment in 961 adults with T2D in need of treatment intensification (HbA1c 8.0-10.0%) on stable metformin ± sulfonylurea. All participants initiated semaglutide treatment with the 0.25 mg dose, doubling every 4 weeks until target dose was reached. The primary objective was to establish superiority of semaglutide 2.0 vs. 1.0 mg on glycemic control; secondary objectives included comparison of the effect on body weight (BW) (confirmatory), safety and tolerability. Baseline characteristics and key results are shown in the Table. Superior HbA1c and BW reductions were shown with semaglutide 2.0 vs. 1.0 mg and a greater proportion of participants achieved HbA1c In conclusion, semaglutide 2.0 mg is superior to 1.0 mg in reducing HbA1c and BW, with a comparable safety profile. Disclosure J. P. Frias: Consultant; Self; 89bio, Inc., Altimmune, Axcella Health Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Gilead Sciences, Inc., Intercept Pharmaceuticals, Inc., Merck & Co., Inc., Novo Nordisk, Pfizer Inc., Sanofi, Research Support; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Bristol-Myers Squibb Company, CymaBay Therapeutics, Eli Lilly and Company, Intercept Pharmaceuticals, Inc., Janssen Pharmaceuticals, Inc., Madrigal Pharmaceuticals, Inc., Merck & Co., Inc., Novartis Pharmaceuticals Corporation, Novo Nordisk, Pfizer Inc., Sanofi, Speaker’s Bureau; Self; Merck & Co., Inc., Sanofi. J. B. Buse: Consultant; Self; Cirius Therapeutics, CSL Behring, Fortress Biotch, Mellitus Health, Moderna, Pendulum Therapeutics, Praetego Inc., Stability Health, Zealand Pharma A/S, Other Relationship; Self; AstraZeneca, Eli Lilly and Company, Novo Nordisk, vTv Therapeutics, Research Support; Self; NovaTarg Therapeutics, Novo Nordisk, Sanofi, Tolerion, Inc., vTv Therapeutics, Stock/Shareholder; Self; Mellitus Health, Pendulum Therapeutics, PhaseBio Pharmaceuticals, Inc., Stability Health. P. Auerbach: Employee; Self; Novo Nordisk A/S. H. S. Bajaj: Other Relationship; Self; Eli Lilly and Company, Novo Nordisk, Research Support; Self; Amgen Inc., AstraZeneca, Boehringer Ingelheim International GmbH, Gilead Sciences, Inc., Kowa Pharmaceuticals America, Inc., Merck & Co., Inc., Sanofi, Tricida, Inc. Y. Fukushima: None. I. Lingvay: Advisory Panel; Self; Bayer Healthcare Pharmaceuticals Inc., Lilly Diabetes, Consultant; Self; TARGET PharmaSolutions, Other Relationship; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Merck Sharp & Dohme Corp., Novo Nordisk, Pfizer Inc., Zealand Pharma A/S, Research Support; Self; Mylan N. V., Sanofi. S. Macura: Employee; Self; Novo Nordisk A/S. A. L. Sondergaard: Stock/Shareholder; Self; Novo Nordisk A/S, Stock/Shareholder; Spouse/Partner; Novo Nordisk A/S. T. Tankova: Advisory Panel; Self; Boehringer Ingelheim International GmbH, Medtronic, Novartis AG, Sanofi, Worwag Pharma, Speaker’s Bureau; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Lilly Diabetes, Merck Sharp & Dohme Corp., Novo Nordisk Pharma Ltd., Sandoz International GmbH, Sanofi, Servier Laboratories. N. Tentolouris: None. Funding Novo Nordisk A/S

665-P: Efficacy and Safety of Once-Weekly Semaglutide 2.0 mg vs. 1.0 mg by Baseline HbA1c and BMI: SUSTAIN FORTE Subgroup Analyses

Once-weekly subcutaneous semaglutide 2.0 mg showed superior efficacy with similar safety vs. 1.0 mg in 961 participants with type 2 diabetes (HbA1c 8.0-10.0%) after 40 weeks in SUSTAIN FORTE. We assessed the effect of semaglutide 2.0 mg vs. 1.0 mg on HbA1c and body weight (BW) in prespecified baseline (BL) HbA1c (<9.0%, ≥9.0%) and BMI (<35, ≥35 kg/m2) subgroups.Mean BL HbA1c was 8.9% and BMI 34.6 kg/m2. For HbA1c and BW, estimated treatment differences favored semaglutide 2.0 mg vs. 1.0 mg across all BL HbA1c and BMI subgroups. Treatment-by-subgroup interactions were nonsignificant (HbA1c, p=0.55 and p=0.41; BW, p=0.40 and p=0.13; Figure A-D). Greater mean HbA1c reductions were observed for both doses in the higher vs. lower BL HbA1c subgroup (Figure A). Conversely, greater mean BW reductions were observed for both doses in the lower vs. higher BL HbA1c subgroup (Figure C). Similar mean HbA1c reductions were observed across BL BMI subgroups (Figure B), while greater mean BW reductions were observed for both doses in the higher vs. lower BL BMI subgroup Figure D). Overall, the incidence of adverse events was similar for both doses and across BL HbA1c and BMI subgroups with no new safety concerns identified.In line with the results in the overall population, semaglutide 2.0 mg provided consistently greater reductions in HbA1c and BW vs. 1.0 mg across BL HbA1c and BMI subgroups.View largeDownload slideView largeDownload slide DisclosureJ. B. Buse: Consultant; Self; Cirius Therapeutics, CSL Behring, Fortress Biotch, Mellitus Health, Moderna, Pendulum Therapeutics, Praetego Inc., Stability Health, Zealand Pharma A/S, Other Relationship; Self; AstraZeneca, Eli Lilly and Company, Novo Nordisk, vTv Therapeutics, Research Support; Self; NovaTarg Therapeutics, Novo Nordisk, Sanofi, Tolerion, Inc., vTv Therapeutics, Stock/Shareholder; Self; Mellitus Health, Pendulum Therapeutics, PhaseBio Pharmaceuticals, Inc., Stability Health. J. P. Frias: Consultant; Self; 89bio, Inc., Altimmune, Axcella Health Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Gilead Sciences, Inc., Intercept Pharmaceuticals, Inc., Merck & Co., Inc., Novo Nordisk, Pfizer Inc., Sanofi, Research Support; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Bristol-Myers Squibb Company, CymaBay Therapeutics, Eli Lilly and Company, Intercept Pharmaceuticals, Inc., Janssen Pharmaceuticals, Inc., Madrigal Pharmaceuticals, Inc., Merck & Co., Inc., Novartis Pharmaceuticals Corporation, Novo Nordisk, Pfizer Inc., Sanofi, Speaker’s Bureau; Self; Merck & Co., Inc., Sanofi. P. Auerbach: Employee; Self; Novo Nordisk A/S. H. S. Bajaj: Other Relationship; Self; Eli Lilly and Company, Novo Nordisk, Research Support; Self; Amgen Inc., AstraZeneca, Boehringer Ingelheim International GmbH, Gilead Sciences, Inc., Kowa Pharmaceuticals America, Inc., Merck & Co., Inc., Sanofi, Tricida, Inc. Y. Fukushima: None. I. Lingvay: Advisory Panel; Self; Bayer Healthcare Pharmaceuticals Inc., Lilly Diabetes, Consultant; Self; TARGET PharmaSolutions, Other Relationship; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Merck Sharp & Dohme Corp., Novo Nordisk, Pfizer Inc., Zealand Pharma A/S, Research Support; Self; Mylan N. V., Sanofi. S. Macura: Employee; Self; Novo Nordisk A/S. A. L. Søndergaard: Stock/Shareholder; Self; Novo Nordisk A/S, Stock/Shareholder; Spouse/Partner; Novo Nordisk A/S. T. Tankova: Advisory Panel; Self; Boehringer Ingelheim International GmbH, Medtronic, Novartis AG, Sanofi, Wörwag Pharma, Speaker’s Bureau; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Lilly Diabetes, Merck Sharp & Dohme Corp., Novo Nordisk Pharma Ltd., Sandoz International GmbH, Sanofi, Servier Laboratories. N. Tentolouris: None.FundingNovo Nordisk A/S

159-OR: Changes of Plasma Phospholipid Fatty Acids in Pregnancy in Relation to the Diagnosis and Treatment of Gestational Diabetes

Background: Previous studies have shown that phospholipids fatty acid (FA) levels in early and mid-pregnancy were associated with incident gestational diabetes mellitus (GDM). However, the subsequent changes of such FAs profile following GDM diagnosis/treatment are understudied. Methods: Within the National Institute of Child Health and Human Development Fetal Growth Studies-Singleton Cohort of 2,802 pregnant women, we ascertained 85 GDM cases according to Carpenter and Coustan criteria, and 85 non-GDM controls matched on maternal age, race/ethnicity, and gestational week at voluntary blood collection. We quantified participants’ plasma FAs concentrations via gas chromatography prior to GDM diagnosis (23-31 weeks) and after GDM treatment initiation (33-39 weeks), respectively. We estimated the GDM-specific FAs changes before and after GDM diagnosis, in reference to the controls using multiple linear mixed models adjusting for major confounders including pre-pregnancy BMI. Results: Eleven FAs exhibited distinctive pre- and post-GDM diagnosis changes among GDM cases. Compared with controls, GDM cases tended to have greater reduction in GDM risk-related FAs such as 14:0 (β -0.22; 95% CI: -0.30, -0.14), 16:0 (-0.02; -0.04, -0.01) and palmitoleic acid (16:1n7) (-0.02; -0.04, -0.01), while greater increment in GDM protective FAs such as heptadecanoic acid (17:0) (0.17; 0.11, 0.22), vaccenic acid (18:1n7) (0.06; 0.03, 0.10) and DHA (22:6n3) (0.08; 0.02, 0.15). Conclusion: Our data identified distinctive FAs changes between pre- and post GDM diagnosis among GDM subjects. These novel findings, along with prior evidence between antenatal FAs and incident GDM, shed lights on further understanding the FAs metabolism in the GDM etiological relevance. Disclosure L. Li: None. Y. Zhu: None. J. Wu: None. D. K. Tobias: None. S. Hinkle: None. R. C. Ma: Other Relationship; Self; AstraZeneca, Medtronic, Research Support; Self; AstraZeneca, Bayer Healthcare Pharmaceuticals Inc., Novo Nordisk, Pfizer Inc., Sanofi-Aventis, Tricida, Inc. M. Y. Tsai: None. C. Zhang: None. Funding Eunice Kennedy Shriver National Institute of Child Health and Human Development(HHSN275200800013C, HHSN275200800002I, HHSN27500006, HHSN275200800003IC, HHSN275200800014C, HHSN275200800012C, HHSN275200800028C, HHSN275201000009C, HHSN275201000001Z)

324-OR: Global Use of SGLT2 Inhibitors and GLP-1 Receptor Agonists in Type 2 Diabetes: Results from DISCOVER

Background: Despite strong evidence of benefit, uptake of newer glucose-lowering medications that reduce cardiovascular risk has been poor. We examined global trends and predictors of use of SGLT2i and GLP-1 RA in patients with T2D. Methods: DISCOVER is a global, prospective, observational study of patients with T2D enrolled from 2014-16 at initiation of 2nd-line glucose-lowering therapy and followed for 3 years. We used hierarchical logistic regression to examine factors associated with use of either SGLT2i or GLP-1 RA at 3 years. Results: Among 14,576 patients from 37 countries, 1579 (10.8%) were started on an SGLT2i (8.7%) or GLP-1 RA (2.2%) at enrollment as 2nd-line therapy. This increased to 16.1% at end of follow-up (13.5% SGLT2i, 3.3% GLP-1 RA). Median use across the 37 countries at 3 years was 19.4% (IQR 8.7-30.6%; range 0-62.7%). Younger age, male sex, higher BMI, and coronary disease were associated with higher use of SGLT2i/GLP-1 RA while peripheral artery disease and kidney disease were associated with lower use. Conclusions: Global use of glucose-lowering medications with cardiovascular benefits has increased over time (particularly SGLT2i) but remains suboptimal, particularly in sub-groups most likely to benefit. Substantial country-level variability exists independent of patient factors, suggesting structural barriers may limit more widespread use of these medications. Disclosure S. V. Arnold: None. K. Khunti: Advisory Panel; Self; Amgen Inc., AstraZeneca, Bayer Healthcare Pharmaceuticals Inc., Berlin-Chemie AG, Lilly Diabetes, Merck Sharp & Dohme Corp., Napp Pharmaceuticals, Novo Nordisk, Roche Pharma, Sanofi-Aventis. M. N. Kosiborod: Consultant; Self; Amgen Inc., Applied Therapeutics, AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Janssen Scientific Affairs, LLC., Merck & Co., Inc., Novo Nordisk, Sanofi, Vifor Pharma Management Ltd., Research Support; Self; AstraZeneca, Boehringer Ingelheim International GmbH. F. Tang: Other Relationship; Self; AstraZeneca. A. Cooper: Employee; Self; AstraZeneca. H. Chen: None. M. B. Gomes: None. W. Rathmann: Advisory Panel; Self; AstraZeneca, Research Support; Self; Novo Nordisk. I. Shimomura: Advisory Panel; Self; AstraZeneca K. K., Daiichi Sankyo, Novo Nordisk Pharma Ltd., Taisho Pharmaceutical Co., Ltd., Consultant; Self; MSD K. K., Novo Nordisk Pharma Ltd., Research Support; Self; Astellas Pharma Inc., Daiichi Sankyo, Eli Lilly Japan K. K., Kowa Company, Ltd., Kyowa Kirin Co., Ltd., Mitsubishi Tanabe Pharma Corporation, MSD K. K., Novartis Pharma K. K., Novo Nordisk Pharma Ltd., Ono Pharmaceutical Co., Ltd., Sanofi K. K., Sumitomo Dainippon Pharma Co., Ltd., Takeda Pharmaceutical Company Limited, Teijin Pharma Limited, Speaker’s Bureau; Self; Astellas Pharma Inc., AstraZeneca K. K., Daiichi Sankyo, Eli Lilly Japan K. K., Kowa Company, Ltd., Kyowa Kirin Co., Ltd., Mitsubishi Tanabe Pharma Corporation, MSD K. K., Nippon Boehringer Ingelheim Co. Ltd., Novo Nordisk Pharma Ltd., Ono Pharmaceutical Co., Ltd., Sanofi K. K., Sanwa Kagaku Kenkyusho, Taiho Pharmaceutical Co., Ltd., Taisho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Company Limited, Teijin Pharma Limited. J. Vora: Advisory Panel; Self; Bayer Inc., Other Relationship; Self; AstraZeneca. H. Watada: Research Support; Self; Abbott Japan Co., Ltd., Astellas Pharma Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Daiichi Sankyo Company, Limited, Kissei Pharmaceutical Co., Ltd., Kowa Company, Ltd., Kyowa Kirin Co., Ltd., Mitsubishi Tanabe Pharma Corporation, MSD Corporation, Novo Nordisk Pharma Ltd., Ono Pharmaceutical Co., Ltd., Sanofi, Sanwa Kagaku Kenkyusho, Sumitomo Dainippon Pharma Co., Ltd., Taisho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Company Limited, Speaker’s Bureau; Self; Astellas Pharma Inc., AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Kyowa Kirin Co., Ltd., Lilly Diabetes, Mitsubishi Tanabe Pharma Corporation, MSD Corporation, Novo Nordisk, Ono Pharmaceutical Co., Ltd., Sanofi, Sanwa Kagaku Kenkyusho, Sumitomo Dainippon Pharma Co., Ltd., Takeda Pharmaceutical Company Limited, Terumo Corporation. Funding AstraZeneca

699-P: Prerandomization Factors Associated with Time-in-Target Glucose Range with Hybrid Closed-Loop Use in a Six-Month Randomized Controlled Trial in Adults with Type 1 Diabetes

Background: In our published trial in 120 adults with type 1 diabetes (T1D), allocation to hybrid closed loop (HCL) increased Continuous Glucose Monitoring (CGM) Time in Range ((TIR), 70-180mg/dL) by 15 percentage points vs. user-determined insulin dosing. Recommended TIR is >70%. Objective: To examine associations of pre-randomization factors with trial-end 3-weeks masked CGM TIR in adults with T1D treated with 6-months HCL. Methods: MDI and non-HCL pump users (no CGM) were randomized 1:1 to 26-weeks HCL (Medtronic 670G) or ongoing standard care. Analyses are on HCL group (n=55): Pre-randomization factors are related to trial-end masked CGM TIR >70 vs. ≤70% and to TIR as a continuous variable. Continuous variables are compared by t-test and binary variables by chi-square with significance at P Results: Table: Pre-randomization characteristics by trial-end TIR > vs. ≤70%. Significant univariate correlations between trial-end TIR as a continuous variable existed for pre-randomization factors: HbA1c (at enrolment and randomization), 1,5-anhydroglucitol, CGM metrics: %TIR (70-180mg/dl), %TIR (70-140mg/dl), mean glucose, SD glucose. Conclusions: The main factor associated with HCL users achieving higher TIR was pre-randomization glycemia. TIR was not associated with age, sex, prior pump use and socioeconomic status. Disclosure A. Jenkins: Advisory Panel; Self; Abbott Diabetes, Sanofi-Aventis, Other Relationship; Self; Amgen Inc., Research Support; Self; Abbott, International Diabetes Federation, JDRF, Medtronic, Mylan N. V. N. Cohen: Advisory Panel; Self; Abbott, AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Lilly Diabetes, Research Support; Self; Ypsomed Group, Speaker’s Bureau; Self; Novo Nordisk. P. G. Colman: None. E. A. Davis: None. J. Holmes-walker: None. A. C. Keech: None. R. Macisaac: Advisory Panel; Self; AstraZeneca, Bayer Healthcare Pharmaceuticals Inc., Novo Nordisk, Servier Laboratories, Speaker’s Bureau; Self; Boehringer Ingelheim International GmbH, Novo Nordisk. C. M. Sims: Stock/Shareholder; Self; Medtronic. V. Sundararajan: None. S. Trawley: None. G. M. Ward: None. A. S. Januszewski: None. T. Jones: None. D. N. O’neal: Advisory Panel; Self; Abbott Diabetes, Medtronic, Sanofi, Research Support; Self; Dexcom, Inc., GlySens Incorporated, Medtronic, Pacific Diabetes Technologies. Jdrf australia adult hybrid closed loop trial: n/a. A. Kirby: None. S. A. Mcauley: Speaker’s Bureau; Self; Sanofi. M. H. Lee: None. B. Paldus: Speaker’s Bureau; Self; Medtronic. S. Vogrin: None. M. De bock: None. M. Burt: None. Funding JDRF (3-SRA-2016-351-M-B)

732-P: CGM-Derived Parameters for Once-Weekly Insulin Icodec vs. Once-Daily Insulin Glargine U100 in Insulin-Naïve Patients with T2D

Insulin icodec* (icodec) is a once-weekly basal insulin in development. This post hoc analysis used data from the NCT03951805 trial to investigate CGM-derived time in, above, below range (TIR, TAR, TBR) and glycemic variability measured as coefficient of variation (CV%). Insulin-naive patients with T2D (N=205) received insulin glargine U100 (IGlar U100; pre-breakfast SMBG target 80-130 mg/dL, adjusted ±4U/day), icodec titration A (80-130 mg/dL, ±21U/week), B (80-130 mg/dL, ±28U/week; most relevant comparator to IGlar U100), or C (70-108 mg/dL, ±28U/week). Treatments were titrated weekly. TIR (70-180 mg/dL), TAR (>180 mg/dL), TBR ( 70% from weeks 7 and 8, TAR decreased to 70% TIR and TBR 70% TIR and TBR Disclosure I. Lingvay: Advisory Panel; Self; Bayer Healthcare Pharmaceuticals Inc., Lilly Diabetes, Consultant; Self; TARGET PharmaSolutions, Other Relationship; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Merck Sharp & Dohme Corp., Novo Nordisk, Pfizer Inc., Zealand Pharma A/S, Research Support; Self; Mylan N. V., Sanofi. R. Beck bang: Employee; Self; Novo Nordisk A/S. M. M. Koefoed: Employee; Self; Novo Nordisk. J. K. Mader: Advisory Panel; Self; Becton, Dickinson and Company, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Medtronic, Roche Diabetes Care, Speaker’s Bureau; Self; Abbott Diabetes, Novo Nordisk A/S, Roche Diabetes Care, Sanofi, Stock/Shareholder; Self; decide Clinical Software GmbH. J. Pettus: Advisory Panel; Self; Novo Nordisk, Sanofi, Consultant; Self; Diasome Pharmaceuticals, Inc., Insulet Corporation, Lilly Diabetes, MannKind Corporation, Tandem Diabetes Care. L. Wagner: None. C. Mathieu: Advisory Panel; Self; Novo Nordisk, Sanofi, Merck Sharp and Dohme Ltd., Eli Lilly and Company, Novartis, AstraZeneca, Boehringer Ingelheim, Roche, Medtronic, ActoBio Therapeutics, Pfizer, Insulet and Zealand Pharma, Research Support; Self; Medtronic, Novo Nordisk, Sanofi and ActoBio Therapeutics, Speaker’s Bureau; Self; Novo Nordisk, Sanofi, Eli Lilly and Company, Boehringer Ingelheim, AstraZeneca and Novartis.

225-OR: Cardiovascular Autonomic Neuropathy and Risk of Heart Failure in Participants with Type 2 Diabetes Enrolled in DEVOTE Trial

Aims: We assessed whether cardiovascular autonomic neuropathy (CAN), as assessed by heart rate variability (HRV), is associated with an increased risk of heart failure (HF) in 6347 patients with type 2 diabetes (T2D) enrolled in the DEVOTE trial with HRV data available. Methods: DEVOTE was a randomized, double-blind trial comparing the impact of insulin degludec to glargine 100 units/mL on cardiovascular outcomes. Indices of HRV were derived from 10-sec standard electrocardiogram at enrollment, with values below the 5th percentile of the cohort defined as abnormal. Time to first hospitalization due to HF was analyzed using Kaplan-Meier survival curves and the log-rank test. Results: A total of 369 (5.8%) had CAN. Participants with and without CAN had significant different [mean(standard deviation)] age [63.4(7.3) and 64.9(7.3) years], A1C [8.9(1.9) and 8.4(1.6)%], body mass index [33.0(7.4) and 33.6(6.8) kg/m2] and number of subjects from minority ethnicity [19.5 and 15.2%], respectively (P Conclusion: These data suggest that CAN may be used for risk stratifying in patients with T2D at risk for developing symptomatic HF. Disclosure R. Pop-busui: Advisory Panel; Self; Novo Nordisk, Consultant; Self; Averitas Pharma, Bayer Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Nevro Corp., Regenacy. L. Ang: None. S. Hayek: Advisory Panel; Self; Walden Biosciences. K. R. Mizokami-stout: None. E. Parvaresh rizi: Employee; Self; Novo Nordisk. I. Lingvay: Advisory Panel; Self; Bayer Healthcare Pharmaceuticals Inc., Lilly Diabetes, Consultant; Self; TARGET PharmaSolutions, Other Relationship; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Merck Sharp & Dohme Corp., Novo Nordisk, Pfizer Inc., Zealand Pharma A/S, Research Support; Self; Mylan N. V., Sanofi. On behalf of the devote study group: n/a. Funding Novo Nordisk

275-OR: Maternal Vitamin D Levels during Pregnancy Is Associated with Childhood Telomere Length: Analysis from a Longitudinal Mother-Child Cohort

Leukocyte telomere length (LTL) is a biomarker of biological aging, and has been associated with metabolic diseases such as type 2 diabetes (T2DM). Insufficient maternal vitamin D (25(OH)D) has also been associated with increased disease risk for many diseases and adverse later life outcomes. The association between maternal and cord blood total 25(OH)D and LTL was examined in mother-child pairs from the HAPO Hong Kong Field Centre, including 815 offspring at age (mean±SD) 6.96 ± 0.44 years. LTL was measured using real-time polymerase chain reaction and serum 25(OH)D2, 25(OH)D3 and 3-epi-25(OH)D3 were measured in maternal blood (at gestation 24-32 weeks) and cord blood by liquid chromatography-mass spectrometry. Children LTL at follow-up was significantly shorter in boys compared to girls (p&amp;lt;0.001) at age 7. Childhood LTL was positively associated with insulin sensitivity according to the Matsuda index after sex and age adjustment (β±SE=0.038±0.017, p=0.022). Multiple linear regression was used to evaluate the relationship between 25(OH)D levels and LTL, with covariate adjustments for child age, sex, body mass index (BMI), systolic blood pressure (SBP), exercise, gestational age, mode of delivery, and maternal age, SBP, parity, smoking, current parental DM status and pre-pregnancy BMI. Childhood LTL positively correlated with total maternal 25(OH)D concentrations (β±SE=0.003±0.001, p=0.001), maternal D3 (β±SE=0.003±0.001, p=0.002) and maternal D3 epimer (β±SE=0.138±0.042, p&amp;lt;0.001), and similar associations were noted for cord D3 epimer (β±SE=0.101±0.045, p=0.024) and cord total 25(OH)D (β±SE=0.1±0.05, p=0.048), even after covariates adjustments. Our findings suggest 25(OH)D, D3 and D3 epimer both in utero and at birth may impact on childhood LTLs, highlighting a potential link between maternal vitamin D and biological aging. Disclosure K. Wong: None. B. E. Metzger: None. W. Lowe: None. W. H. Tam: None. R. C. Ma: Other Relationship; Self; AstraZeneca, Medtronic, Research Support; Self; AstraZeneca, Bayer Healthcare Pharmaceuticals Inc., Novo Nordisk, Pfizer Inc., Sanofi-Aventis, Tricida, Inc. F. Cheng: None. D. Mao: None. C. K. P. Lim: Stock/Shareholder; Self; GemVCare Ltd. R. Wang: None. C. H. Tam: None. M. A. Joglekar: None. A. A. Hardikar: None. A. Jenkins: Advisory Panel; Self; Abbott Diabetes, Sanofi-Aventis, Other Relationship; Self; Amgen Inc., Research Support; Self; Abbott, International Diabetes Federation, JDRF, Medtronic, Mylan N. V.

721-P: Efficacy and Safety of Basal-First Titration Order in Patients with Type 2 Diabetes (T2D) Receiving Short-Term Intensive Insulin Therapy (SIT)

To titrate basal and bolus insulin sequentially or simultaneously during SIT remains controversial. Here we report an easy titration order verified in a 7-10 day SIT period. Insulin naive Chinese T2D adults receiving stable doses of metformin and 1-2 oral antihyperglycemic drugs with HbA1c 7.5%-11.0% were treated with once-daily insulin glargine 100 U/mL (Gla-100) and thrice-daily insulin glulisine (Glu) for 7-10 days titrated to achieve a fasting blood glucose (FBG) In conclusion, when starting basal-bolus regimen in SIT, basal-first titration order was effective, fast to target and well tolerated in Chinese T2D patients. Disclosure L. Guo: Consultant; Self; AstraZeneca, Bayer Healthcare Pharmaceuticals Inc., BD, Eli Lilly and Company, Merck & Co., Inc., Merck Sharp & Dohme Corp., Novartis AG, Novo Nordisk, Sanofi China. J. Liu: Employee; Self; Sanofi China. X. Zhang: None. N. Cui: Employee; Self; Sanofi China. H. Yin: None. Y. Mu: Speaker’s Bureau; Self; Abbott, Boehringer Ingelheim Pharmaceuticals, Inc., Lilly Diabetes, Novo Nordisk Inc., Sanofi-Aventis. H. Wan: None. J. Wang: None. B. Xu: None. G. Wang: None. C. Jiang: None. L. Liang: None. W. Feng: Employee; Self; Sanofi China. Funding Sanofi China (NCT03359837)

1052-P: Clinical Characteristics of Osteoporosis in Postmenopausal Women with Type 2 Diabetes Mellitus

Objective: To investigate clinical characteristics and risk factors of osteoporosis in postmenopausal women with type 2 diabetes mellitus. Method: A total of 410 postmenopausal women with type 2 diabetes of natural menopause with no history of fracture were collected from outpatients of Beijing Hospital (Oct 2017 - Nov 2019). Bone mineral density (BMD) at lumbar spine L1-L4 and hip was measured using dual-energy X-ray absorptiometry. Biochemical markers of bone and glucose metabolism were evaluated. Patients were divided into three groups based on BMD: A (osteoporosis): T ≤-2.5 SD; B (osteopenia) -2.5 &amp;lt; T ≤ -1 SD; C (normal bone mineral density) T &amp;gt; -1 SD. Statistical differences of age, menopausal age, diabetes age, BMI and biochemical indexes were compared between groups. Result: 1. Case number based on lumbar spine BMD: 189 in A (46.1%), 147 in B (35.9%), and 74 in C (18.0%). ANOVA analysis showed group A patients had the highest age (F 5.698, p 0.004), age of diabetes onset (F 7.596, p 0.001), ALP (F 3.231, p 0.041) and menopausal duration (F 7.596, p 0.001), but the lowest BMI (F 11.456, p 0.000). Logistic multivariate regression showed body mass index is an independent risk factor for osteoporosis in postmenopausal women with type 2 diabetes [A vs. C: OR1.224 (95% CI 1.106-1.355, p 0.000); A vs. B: OR1.172 (95% CI 1.079-1.274, p 0.000].2. Case number based on femoral neck BMD: 159 in A (38.8%), 188 in B (45.9%), 63 in C (15.3%). ANOVA analysis showed group A patients had the highest age (F 21.484, p 0.000), age of diabetes onset (F 10.125, p 0.000) and PTH (F3.691, 0.026), but the lowest BMI (F 11.456, p 0.000). Logistic multivariate regression showed body mass index is an independent risk factor for osteoporosis in postmenopausal women with type 2 diabetes [A vs. C: OR1.267 (95% CI 1.120-1.433, p 0.000); A vs. B: OR1.195 (95% CI1.099-1.301, p 0.000)]. Conclusion: Osteoporosis in postmenopausal women with type 2 diabetes is associated with older age, longer menopause duration, older age of diabetes onset and lower BMI. Disclosure Y. Wang: None. Z. Lina: None. L. Guo: Consultant; Self; AstraZeneca, Bayer Healthcare Pharmaceuticals Inc., BD, Eli Lilly and Company, Merck &amp; Co., Inc., Merck Sharp &amp; Dohme Corp., Novartis AG, Novo Nordisk, Sanofi China.

212-OR: Closed-Loop Increases Time-in-Range in Older Adults with Type 1 Diabetes Compared with Sensor-Augmented Pump Therapy: A Randomized Crossover Trial

Background: Older adults with type 1 diabetes (T1D) have unique health challenges and have not been specifically studied in previous closed-loop (CL) trials. Objective: To assess the efficacy and safety of CL compared with sensor-augmented pump (SAP) therapy in older adults with T1D. Methods: We conducted a two-stage randomized, crossover trial comparing 4 months of CL vs. SAP. Adults aged ≥60 years with T1D ≥10 years and using an insulin pump were eligible. SAP (with continuous glucose monitoring [CGM] alerts and optional insulin delivery suspension on low glucose) and multi-disciplinary education were provided during run-in, then CL and SAP stages were undertaken in random order. The primary outcome was CGM time in range (TIR) 70-180 mg/dL comparing the final 3 months of each stage. Results: Thirty adults (mean±SD age 67±5 years, T1D duration 37±15 years and HbA1c 59±9 mmol/mol [7.6±0.9%]) participated. Ten participants (33%) had impaired awareness of hypoglycemia (Gold score ≥4); all were cognitively healthy, and none met the criteria for frailty. CGM TIR was 75.1±6.3% during CL and 69.0±9.1% during SAP (mean difference 6.2% [95% CI 4.3, 8.0]; p &amp;lt;0.001). All pre-specified CGM metrics favored CL over SAP; benefits were greater overnight. CL reduced CGM time &amp;lt;70 mg/dL compared with SAP during 24 h/day (median [IQR] 1.2% [0.6, 1.7] vs. 1.7% [1.0, 2.5], respectively; p &amp;lt;0.001) and overnight (0.4% [0.2, 0.9] vs. 1.3% [0.8, 2.5], respectively; p &amp;lt;0.001). HbA1c at CL vs. SAP stage end was 56 mmol/mol (54, 59) vs. 59 mmol/mol (54, 62), respectively (p = 0.11). No serious hypoglycemic events occurred; one episode of diabetic ketoacidosis occurred during SAP. Conclusions: In this trial involving adults with T1D aged ≥60 years, CL increased TIR and reduced time below range compared with SAP, particularly overnight. The therapeutic benefit was evident even with relatively low baseline HbA1c. Further research is needed to understand the long-term clinical benefit. Disclosure S. A. Mcauley: Speaker’s Bureau; Self; Sanofi. N. A. O’regan: None. V. Sundararajan: None. G. M. Ward: None. R. Macisaac: Advisory Panel; Self; AstraZeneca, Bayer Healthcare Pharmaceuticals Inc., Novo Nordisk, Servier Laboratories, Speaker’s Bureau; Self; Boehringer Ingelheim International GmbH, Novo Nordisk. S. Vogrin: None. S. Trawley: None. P. G. Colman: None. S. Fourlanos: Advisory Panel; Self; Pfizer Foundation, Speaker’s Bureau; Self; AstraZeneca, Eli Lilly and Company. C. Grills: None. M. H. Lee: None. A. Mohammad alipoor: None. D. N. O’neal: Advisory Panel; Self; Abbott Diabetes, Medtronic, Sanofi, Research Support; Self; Dexcom, Inc., GlySens Incorporated, Medtronic, Pacific Diabetes Technologies. Funding JDRF (3-SRA-2018-667-M-R); Diabetes Australia

83-OR: Influence of Baseline Characteristics on Weight Loss with Semaglutide 2.4 mg in Adults with Overweight/Obesity and Type 2 Diabetes (STEP 2)

Weight loss (WL) with semaglutide 2.4 mg vs. placebo (PBO) in the STEP 2 trial was analyzed according to baseline characteristics. STEP 2 was a 68-week RCT (NCT03552757). Adults (N=1210) with BMI ≥27 kg/m2 and type 2 diabetes (T2D; HbA1c 7-10% [53-86 mmol/mol]) were randomized to once‑weekly s.c. semaglutide 2.4 mg, 1.0 mg (data not shown) or PBO. Categorical WL was evaluated at week 68 by baseline age, sex, race, body weight (BW), HbA1c, and diabetes therapy. The odds of achieving WL ≥5% or ≥10% for these parameters were compared using post-hoc logistic regression analyses (not controlled for multiplicity). At week 68, the proportions of patients (pts) with WL ≥5% and ≥10% were 73.2% and 49.9% for semaglutide 2.4 mg vs. 27.6% and 7.1% for PBO. Pts were significantly more likely to achieve WL ≥5% or ≥10% with semaglutide 2.4 mg vs. PBO in most subgroups (Table). There were no significant interactions for any subgroups, except sex; the odds ratios for achieving WL ≥5% or ≥10% with semaglutide 2.4 mg vs. PBO were more than double for females vs. males (p Disclosure I. Lingvay: Advisory Panel; Self; Bayer Healthcare Pharmaceuticals Inc., Lilly Diabetes, Consultant; Self; TARGET PharmaSolutions, Other Relationship; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Merck Sharp & Dohme Corp., Novo Nordisk, Pfizer Inc., Zealand Pharma A/S, Research Support; Self; Mylan N. V., Sanofi. W. Garvey: None. L. Faerch: Employee; Self; Novo Nordisk A/S, Stock/Shareholder; Self; Novo Nordisk A/S. A. Koroleva: Employee; Self; Novo Nordisk A/S. R. F. Kushner: Advisory Panel; Self; Novo Nordisk A/S. C. Le roux: Advisory Panel; Self; Boehringer Ingelheim International GmbH, GI Dynamics, Herbalife International of America, Inc., Johnson & Johnson, Medtronic, Novo Nordisk A/S. S. Lim: None. O. Mosenzon: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., BOL Pharma, Eli Lilly and Company, Merck & Co., Inc., Novo Nordisk, Sanofi, Research Support; Self; AstraZeneca, Novo Nordisk, Speaker’s Bureau; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Merck & Co., Inc., Novo Nordisk, Sanofi. T. A. Wadden: Advisory Panel; Self; Novo Nordisk, Weight Watchers International, Inc. S. O. R. Wallenstein: Employee; Self; Novo Nordisk. Funding Novo Nordisk A/S

606-P: Higher Derived Time-in-Range with IDegLira vs. Insulin Glargine U100 in Patients with T2D

Aims: To compare derived time in range (dTIR) with insulin degludec/liraglutide (IDegLira) and insulin glargine 100 units/mL (IGlar U100) in patients with type 2 diabetes (T2D). Methods: Data from DUAL V, a trial of patients with T2D uncontrolled on IGlar U100 randomized to switch to IDegLira or up-titration of IGlar U100 (+metformin; n=557), and DUAL VIII, a durability trial of insulin-naive patients with T2D randomized to either IDegLira or IGlar U100 (+ oral antidiabetic drugs; n=1012), were evaluated post hoc. Self-monitored blood glucose profiles (weeks 0, 12, and 26 [DUAL V] or weeks 0, 26, and 104 [DUAL VIII]) were used to derive the proportion of available readings within (dTIR: 70-180 mg/dL [3.9-10 mmol/L]), below (dTBR: 180 mg/dL [>10 mmol/L]) target range. Results: Estimated treatment differences (IDegLira− IGlar U100) for change from baseline to end of treatment (EOT) in dTIR were significantly greater with IDegLira vs. IGlar U100 (Figure). The proportion of patients achieving ≥70% dTIR at EOT with IDegLira and IGlar U100, respectively, was 62% and 60% in DUAL V, and 50% and 26% in DUAL VIII; the proportion achieving a ≥5% increase in dTIR from baseline to EOT was 63% in both groups in DUAL V, and 44% and 25%, respectively, in DUAL VIII. Conclusion: IDegLira was associated with significantly greater dTIR vs. IGlar U100 in insulin-experienced and insulin-naive patients with T2D. Disclosure A. Philis-tsimikas: Advisory Panel; Self; Bayer Inc., Lilly Diabetes, Medtronic, Novo Nordisk, Consultant; Self; Sanofi-Aventis, Employee; Spouse/Partner; Ionis, Other Relationship; Self; Merck & Co., Inc., Research Support; Self; Dexcom, Inc., Lilly Diabetes, Medtronic, Novo Nordisk, Sanofi-Aventis. V. R. Aroda: Consultant; Self; Applied Therapeutics, Duke, Novo Nordisk, Pfizer Inc., Sanofi, Employee; Spouse/Partner; Janssen , Merck , Research Support; Self; Applied Therapeutics, Eli Lilly and Company, Fractyl , Medpace, Medpace, Novo Nordisk, Premier , Sanofi, Stock/Shareholder; Spouse/Partner; Janssen, Merck. C. De block: Advisory Panel; Self; A. Menarini Diagnostics, Abbott Diagnostics, AstraZeneca, Boehringer Ingelheim , Eli Lilly and Company, MSD, Novartis AG, Novo Nordisk, Roche Diagnostics, Sanofi, Research Support; Self; AstraZeneca, Novo Nordisk, Speaker9s Bureau; Self; A. Menarini Diagnostics, Abbott Diagnostics, Boehringer Ingelheim , Eli Lilly and Company, Novo Nordisk, Sanofi. L. K. Billings: Advisory Panel; Self; Bayer Inc., Lilly Diabetes, Novo Nordisk, Sanofi. E. Hachmann-nielsen: Employee; Self; Novo Nordisk A/S. A. Liebl: Advisory Panel; Self; AstraZeneca, Becton, Dickinson and Company, Boehringer Ingelheim International GmbH, Eli Lilly and Company, MSD, Novo Nordisk, Roche, Speaker9s Bureau; Self; AstraZeneca, Bayer, Becton, Dickinson and Company, Boehringer Ingelheim International GmbH, Bristol Myers Squibb , Dexcom, Inc., Eli Lilly and Company, Medtronic, MSD, Novo Nordisk, OmniaMed, Roche, Sanofi. R. Sivarathinasami: Employee; Self; Novo Nordisk Service Centre India Private Ltd. J. M. D9cruz: Employee; Self; NovoNordisk GBS. I. Lingvay: Advisory Panel; Self; Bayer Healthcare Pharmaceuticals Inc., Lilly Diabetes, Consultant; Self; TARGET PharmaSolutions, Other Relationship; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Merck Sharp & Dohme Corp., Novo Nordisk, Pfizer Inc., Zealand Pharma A/S, Research Support; Self; Mylan N. V., Sanofi. Funding Novo Nordisk A/S

71-LB: Meta-analysis of Two Real-World Chart Review Studies to Determine the Effectiveness of FreeStyle Libre Flash Glucose Monitoring System on HbA1c in Adults with Type 2 Diabetes Managed with Basal Insulin

Two retrospective chart review studies evaluated the effectiveness of the FreeStyle Libre® Flash Glucose Monitoring System on HbA1c when used by adults with type 2 diabetes (T2D) in a real-world setting. Each study aimed to determine the effect of FreeStyle Libre when used for between 3 months to 6 months on HbA1c. Each study population included adults on a basal insulin regimen for at least 1 year who had been using FreeStyle Libre regularly for at least 3 months and with HbA1c between 8.0 and 12.0% (64 to 108 mmol/mol). Pregnant patients were excluded, as were patients on dialysis. This meta-analysis comprised of a total of 191 records from basal insulin using patients with T2D from 14 medical centers across Canada and the US. On average, HbA1c was 9.2±1.0% (76.8±10.7 mmol/mol) prior to FreeStyle Libre use, age was 60.0±11.3 years and average duration of insulin use 4.3±3.3 years (mean±SD), 95.8% of patients were on oral antidiabetic medications and 60.2% were male. Renal and CVD complications were reported by 31.4% and 28.3% of patients, respectively. HbA1c results were recorded between 90 and 194 days from the start of use of FreeStyle Libre, between December 2017 and March 2020. Overall mean change in HbA1c, after at least 3 months of using FreeStyle Libre, was significantly reduced by 1.1±0.14% (mean±SE); p&amp;lt;0.0001, with moderate to high heterogeneity between centers (Q=43.9, I2=74.9, p&amp;lt;0.0001) explained by differences in initial HbA1c between centers. No significant differences were detected between: age group, sex, BMI or duration of insulin use. This meta-analysis of two real-world, chart review studies concludes that people with T2D on basal insulin therapy, using FreeStyle Libre for between 3 to 6 months significantly reduced HbA1c. Disclosure A. L. Carlson: Board Member; Self; JDRF, Other Relationship; Self; Medtronic, Research Support; Self; Abbott Diabetes, Dexcom, Inc., Eli Lilly and Company, Novo Nordisk, Omnipod, Sanofi, UnitedHealth Group. T. D. Daniel: Advisory Panel; Self; Abbott Diabetes, Bayer Healthcare Pharmaceuticals Inc. A. Desantis: None. S. Jabbour: None. E. Karslioglu-french: None. D. F. Kruger: Advisory Panel; Self; Abbott Diabetes, Novo Nordisk, Sanofi US, Research Support; Self; Abbott Diabetes, Dexcom, Inc., Novo Nordisk, Speaker’s Bureau; Self; Dexcom, Inc., Eli Lilly and Company, Novo Nordisk, Stock/Shareholder; Self; Pendulum Therapeutics. E. Miller: Advisory Panel; Self; Abbott Diabetes, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Novo Nordisk Inc., Research Support; Self; Pendulum Therapeutics, Research Support; Spouse/Partner; Abbott Diabetes. K. Ozer: Research Support; Self; Abbott Diabetes, AbbVie Inc., Eli Lilly and Company, Novo Nordisk, Senseonics, Speaker’s Bureau; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Novo Nordisk. T. Elliott: Advisory Panel; Self; Eli Lilly and Company, Novo Nordisk, Other Relationship; Self; Abbott Diabetes. Funding Abbott Diabetes Care

416-P: Palmitic Acid-Induced Schwann Cells Apoptosis and Oxidative Stress in Diabetes Peripheral Neuropathy

Diabetic peripheral neuropathy (DPN) is one of the most common chronic complications of diabetes, but its pathogenesis has not been fully clarified. Schwann cells play an indispensable role in maintaining the structure and function of neurons, but the mechanism is complex. High fatty acid is the characteristic of diabetic complications. We used RSC96 to investigate the effects of palmitic acid on apoptosis and mitochondrial function. Our results showed increased ROS production and mitochondrial oxidative stress, increased apoptosis, and decreased ATP generation. DPN was aggravated by Schwann cell apoptosis, oxidative stress and mitochondrial dysfunction. Although the interaction between Schwann damage and neuronopathy remains to be elucidated, the present study may provide ideas for novel pathogenetic pathways of DPN.View largeDownload slideView largeDownload slideView largeDownload slideView largeDownload slideDisclosureJ. Fan: None. L. Guo: Consultant; Self; AstraZeneca, Bayer Healthcare Pharmaceuticals Inc., BD, Eli Lilly and Company, Merck & Co., Inc., Merck Sharp & Dohme Corp., Novartis AG, Novo Nordisk, Sanofi China.

64-LB: Glucose Control after Initiation of Flash Glucose Monitoring in Type 2 Diabetes Managed with Basal Insulin: A Retrospective Real-World Chart Review Study from the U.S.

This retrospective, real-world, chart review study determined the effectiveness of the FreeStyle Libre® Flash Glucose Monitoring System on HbA1c when used by adults with type 2 diabetes (T2D) in a real-world setting between 3 months to 6 months after starting FreeStyle Libre. The study population included adults on a basal insulin regimen for at least 1 year, with HbA1c between 8.0 and 12.0% (64 to 108 mmol/mol), using FreeStyle Libre regularly for at least 3 months. Pregnant patients were excluded, as were patients on dialysis. A total of 100 records from basal insulin using patients with T2D from 8 clinical sites in the US were included in this chart review. Mean HbA1c was 9.4±1.0% (79.2±11.1 mmol/mol), prior to FreeStyle Libre use, age was 56.0±10.3 years, BMI was 36.1±7.8 kg/m2 and average duration of insulin use 4.5±3.5 years (mean±SD); 96.0% of patients were on oral anti-diabetic medications in addition to basal insulin and 52.0% were male. HbA1c results were recorded between 90 to 194 days from the start of use of FreeStyle Libre, between December 2017 and March 2020. To minimise selection bias records were selected on a systematic basis. After at least 3 months of using FreeStyle Libre in addition to their usual clinical care, HbA1c (primary outcome) was significantly reduced by 1.4±1.3% (mean±SD); p&amp;lt;0.0001. Sub-group analysis by baseline HbA1c (&amp;lt;9.0%, ≥9.0%) showed both groups significantly reduced HbA1c; with reductions of 0.8±0.7%, p&amp;lt;0.0001 and 1.7±1.4%, p&amp;lt;0.0001, respectively. This real-world, chart review study concluded that people with T2D on basal insulin therapy, using FreeStyle Libre for between 3 to 6 months significantly reduced HbA1c. Disclosure A. L. Carlson: Board Member; Self; JDRF, Other Relationship; Self; Medtronic, Research Support; Self; Abbott Diabetes, Dexcom, Inc., Eli Lilly and Company, Novo Nordisk, Omnipod, Sanofi, UnitedHealth Group. T. D. Daniel: Advisory Panel; Self; Abbott Diabetes, Bayer Healthcare Pharmaceuticals Inc. A. Desantis: None. S. Jabbour: None. E. Karslioglu-french: None. D. F. Kruger: Advisory Panel; Self; Abbott Diabetes, Novo Nordisk, Sanofi US, Research Support; Self; Abbott Diabetes, Dexcom, Inc., Novo Nordisk, Speaker’s Bureau; Self; Dexcom, Inc., Eli Lilly and Company, Novo Nordisk, Stock/Shareholder; Self; Pendulum Therapeutics. E. Miller: Advisory Panel; Self; Abbott Diabetes, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Novo Nordisk Inc., Research Support; Self; Pendulum Therapeutics, Research Support; Spouse/Partner; Abbott Diabetes. K. Ozer: Research Support; Self; Abbott Diabetes, AbbVie Inc., Eli Lilly and Company, Novo Nordisk, Senseonics, Speaker’s Bureau; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Novo Nordisk. Funding Abbott Diabetes Care

Biomarker analysis of phase (Ph) IB trial of radium-223 (Rad) and niraparib (Nira) in patients (Pts) with metastatic castrate-resistant prostate cancer (mCRPC) (NiraRad).

5036 Background: Rad is an alpha particle emitter that causes DNA double strand breaks and has been FDA-approved for use in mCRPC pts with bone metastases. PARP-1 activity critically supports androgen receptor (AR) activity in mCRPC and potentiates AR-dependent DNA damage response pathways that promote prostate cancer cell survival. Nira is a potent and selective PARP-1/2 inhibitor that has shown single agent clinical activity in mCRPC. We previously reported the safety of targeting the PARP-1/AR axis with Nira in combination with Rad. Herein we describe the results of an exploratory biomarker analysis. Methods: The primary objective of NiraRad is to determine the optimum Ph II dose of Nira plus Rad (55 kBq/kg of body weight IV every 4 weeks (wks) x 6) in pts with and without prior chemotherapy (docetaxel). Pts were enrolled to one of three dose levels of Nira (100, 200, or 300 mg PO daily). All cohorts were combined for exploratory biomarker analysis using Nanostring PanCancer Driver and Immune Pathways panels and the nSolver Advanced analysis module was performed on blood obtained from 23 pts at baseline, cycle (C) 1 day (D) 15, and C3D15. A favorable response was defined as any PSA reduction at week 12 or treatment (tx) duration &gt; 18 wks, the median time on tx in the cohort of pts analyzed. A threshold of &gt; 2 fold (X) differentially expressed genes was used. Results: Of the 23 pts with biomarker data, 7 (30%) experienced PSA reductions and 11 (48%) received tx for &gt; 18 wks, 6 of which also had PSA reductions. Exploratory analysis revealed that the PI3K/Ras, MAPK, and transcriptional misregulation pathways were differentially regulated in pts who had favorable responses. The top downregulated gene, PAX5, which has been shown to promote prostate cancer growth, was decreased at C1D15 (2.7X, p &lt; 0.01) and C3D15 (4.8X, p &lt; 0.001) in pts with tx duration &gt; 18 wks and at baseline in pts who had PSA reductions (3.1X, p &lt; 0.05). Immune pathways analysis suggested downregulation of immunosuppressive B-cell (plasma cell) and upregulation of NK and T cell pathways in pts with tx duration &gt; 18 wks. Conclusions: Previously Nira and Rad have been shown to have acceptable tolerability in mCRPC pts. This exploratory analysis suggests potential response biomarkers that warrant further investigation. Managed by: the Prostate Cancer Clinical Trials Consortium; Funded by: Janssen Pharmaceuticals and Bayer Healthcare Pharmaceuticals, Inc. Clinical trial information: NCT03076203.

R-CHOP Versus R-Bendamustine with or without Rituximab Maintenance in Newly Diagnosed Follicular Lymphoma Patients with High SUV at Baseline PET

R-CHOP Versus R-Bendamustine with or without Rituximab Maintenance in Newly Diagnosed Follicular Lymphoma Patients with High SUV at Baseline PET

Patient-Reported Outcomes Among Patients with High-Risk Untreated Follicular Lymphoma (FL) Randomized to Bendamustine/Rituximab (BR) or Bendamustine/Rituximab with Bortezomib (BVR) Therapy: Results from the ECOG-ACRIN E2408 Study

Patient-Reported Outcomes Among Patients with High-Risk Untreated Follicular Lymphoma (FL) Randomized to Bendamustine/Rituximab (BR) or Bendamustine/Rituximab with Bortezomib (BVR) Therapy: Results from the ECOG-ACRIN E2408 Study

Prognostication for Advanced Stage Hodgkin Lymphoma (HL) in the Modern Era: A Project from the Hodgkin Lymphoma International Study for Individual Care (HoLISTIC) Consortium

Prognostication for Advanced Stage Hodgkin Lymphoma (HL) in the Modern Era: A Project from the Hodgkin Lymphoma International Study for Individual Care (HoLISTIC) Consortium