Corcept Therapeutics Research Articles

38-LB: Physical Activity and Glycemia among Young Adults with Type 1 Diabetes and Overweight or Obesity—Results from Advancing Care for Type 1 Diabetes and Obesity Network (ACT1ON)

The ACT1ON pilot study evaluated the feasibility of three dietary strategies to optimize weight and glycemic management among young adults with T1D and overweight or obesity. As a secondary measure, self-reported physical activity (PA) was collected at baseline, 3-, 6-, and 9-months from 68 young adults with T1D (age 25.5 ± 3.1 years, 72.1% female, HbA1c 7.9 ± 1.8%, BMI 30.4 (27.9 - 33.9)) . Using the Global Physical Activity Questionnaire (GPAQ, n=195) and Previous Day Physical Activity Recalls (PDPAR, n=123) , we estimated weekly minutes of moderate-to-vigorous physical activity (MVPA) . Following the COVID-19 outbreak, a subset of participants wore Garmin Vivosmart4® PA trackers for two weeks at each visit (44 measurements from 27 participants) . Mixed effects regression models assessed the relationship between weekly minutes of MVPA and HbA1c using each PA measure. Median weekly minutes of MVPA were 33% lower following the COVID-19 outbreak compared to pre-pandemic PA levels (p=0.02) per the GPAQ, but not PDPAR (-7.7%, p=0.34) . After adjusting for design, demographic, clinical, and dietary variables, a 1 standard deviation increase in weekly minutes of MVPA (GPAQ) was associated with an absolute increase of 0.27% HbA1c (p>0.001) . A small, statistically non-significant association was observed for PDPAR (β=0.13, p=0.19) ; however, we observed a borderline statistically significant association using the PA tracker data (β=0.231, p=0.08) , despite a smaller sample size (n=44) . These results suggest that among young adults with T1D and overweight and obesity, higher levels of PA may lead to challenges in achieving optimal glycemia. Future work is needed to determine how to best support young adults with T1D and overweight and obesity in attaining both their PA and glycemic management goals. Disclosure F. R. Muntis: None. R. E. Pratley: Other Relationship; Bayer AG, Corcept Therapeutics, Dexcom, Inc., Hanmi Pharm. Co., Ltd., Merck & Co., Inc., Metavention, Novo Nordisk, Pfizer Inc., Poxel SA, Sanofi, Scohia Pharma Inc., Sun Pharmaceutical Industries Ltd. K. Corbin: None. E. J. Mayer-davis: None. D. P. Zaharieva: Research Support; Insulet Corporation, International Society for Pediatric and Adolescent Diabetes, Leona M. and Harry B. Helmsley Charitable Trust. D. Igudesman: None. A. Cristello: None. J. Thomas: None. N. Arrizon- ruiz: None. J. Hooper: None. A. Addala: None. J. Crandell: n/a. D. M. Maahs: Advisory Panel; Abbott Diabetes, Eli Lilly and Company, Medtronic, Novo Nordisk, Sanofi, Consultant; Aditx Therapeutics, Inc., Biospex. Funding National Institutes of Health (1DP3DK113358-01)

592-P: Living with Type 1 Diabetes (T1DM) as an Older Adult: A Qualitative Study Examining Experiences and Attitudes about Continuous Glucose Monitoring (CGM)

There is a growing population of adults over the age of 65 years with T1DM, but their lived experiences have not been well-characterized, especially in the context of evolving advances in self-management technology. We conducted focus groups with adults 65+ yrs with T1DM to characterize their perspectives surrounding T1DM and its management, focusing on CGM experiences. Participants were recruited from a US academic medical center and encouraged to bring a caregiver. Focus groups were stratified by CGM use, facilitated by standardized questions, audiotaped and transcribed. A team-based, inductive coding approach using ATLAS.ti identified themes. There were 33 adults (mean age 73.3±4.3 years [range 66-85]; 55% women, 82% non-Hispanic white, 12% non-CGM users, 83% pump users, 12% caregivers) . Five CGM-related themes were identified from all participants, including adoption challenges and complex clinical and psychosocial effects (Table) . Caregiver participants emphasized increased security with CGM use. Patient participants expressed a prevalent “survivor” mentality and a desire for increased peer support and strategies to minimize intrusiveness of T1DM management. Findings reinforce that older adults’ experiences with T1DM and CGM necessitate individualized psychosocial and tactical support for management and adoption of new technology. Disclosure A.Kahkoska: None. L.A.Young: Research Support; Bayer AG, Boehringer Ingelheim International GmbH, Dexcom, Inc., Eli Lilly and Company, Novo Nordisk, vTv Therapeutics. K.Hassmiller lich: None. A.Cristello: None. C.Smith: None. S.R.Thomas: None. J.Batsis: None. E.J.Mayer-davis: None. M.R.Kosorok: n/a. R.E.Pratley: Other Relationship; Bayer AG, Corcept Therapeutics, Dexcom, Inc., Hanmi Pharm. Co., Ltd., Merck & Co., Inc., Metavention, Novo Nordisk, Pfizer Inc., Poxel SA, Sanofi, Scohia Pharma Inc., Sun Pharmaceutical Industries Ltd. R.S.Weinstock: Research Support; Boehringer Ingelheim International GmbH, Dexcom, Inc., Diasome, Eli Lilly and Company, Insulet Corporation, Kowa Pharmaceuticals America, Inc., Medtronic, Novo Nordisk, Tandem Diabetes Care, Inc., Tolerion, Inc. Funding ARK is supported by the National Center for Advancing Translational Sciences, National Institutes of Health, through Grant KL2TR002490. The project was supported by UL1TR002489 from the Clinical and Translational Science Award program of the Division of Research Resources, National Institutes of Health. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.

865-P: Long-Term Ertugliflozin Treatment and Incidence of Hypoglycemia: Analyses from VERTIS CV

This analysis assessed the incidence and total events of hypoglycemia in VERTIS CV (NCT01986881) , the cardiovascular (CV) outcome trial for ertugliflozin (ERTU) in patients (pts) with type 2 diabetes and atherosclerotic CV disease. Hypoglycemia was categorized as level 1, a documented symptomatic event with plasma glucose (PG) ≤70 mg/dL (prespecified) ; level 2, a documented event with PG <54 mg/dL (post hoc) ; level 3, a severe event requiring assistance (prespecified) . Time to first HYPO-broad (levels 1+2+3) and HYPO-strict (levels 2+3) were analyzed by a Cox proportional hazards model. Kaplan-Meier estimates were plotted. Exposure-adjusted event rates for total (first + recurrent) HYPO-broad and -strict were analyzed. Overall, 8246 pts were randomized, mean follow-up was 3.5 yrs. The incidence rate (ERTU vs PBO) of first HYPO-broad was 14.3 vs. 16.2/100 pt-yrs; adjusted hazard ratio [aHR], 95% CI: 0.93 [0.85, 1.00] and HYPO-strict was 9.5 vs. 11.1/100 pt-yrs; aHR: 0.89 [0.81, 0.97] [Figure A]. Exposure-adjusted event rates were lower in ERTU vs PBO [Figure B]. The increase in percentage of insulin users (end of study vs. baseline) was less with ERTU (3.5% 5 + 15 mg) compared with PBO (6.2%) . In VERTIS CV, pts randomized to ERTU had a lower risk of hypoglycemia, including first and recurrent events, than PBO-treated pts. This may in part be due to the lesser increase in insulin users with ERTU vs. PBO. Disclosure S.Dagogo-jack: Consultant; AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Janssen Pharmaceuticals, Inc., Medtronic, Merck & Co., Inc., Sanofi. R.E.Pratley: Other Relationship; Bayer AG, Corcept Therapeutics, Dexcom, Inc., Hanmi Pharm. Co., Ltd., Merck & Co., Inc., Metavention, Novo Nordisk, Pfizer Inc., Poxel SA, Sanofi, Scohia Pharma Inc., Sun Pharmaceutical Industries Ltd. C.P.Cannon: Advisory Panel; Alnylam Pharmaceuticals, Inc., Amarin Corporation, Amgen Inc., Amryt Pharma Plc, Applied Therapeutics, Ascendis Pharma A/S, Boehringer Ingelheim International GmbH, Bristol-Myers Squibb Company, Eli Lilly and Company, Janssen Pharmaceuticals, Inc., Lexicon Pharmaceuticals, Inc., Merck & Co., Inc., Pfizer Inc., Rhoshan, Sanofi, Research Support; Amgen Inc., Better Therapeutics, Boehringer Ingelheim International GmbH, Bristol-Myers Squibb Company, Daiichi Sankyo, Janssen Pharmaceuticals, Inc., Merck & Co., Inc., Novo Nordisk, Pfizer Inc. D.Cherney: Other Relationship; AbbVie Inc., AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Janssen Research & Development, LLC, Lilly, Maze, BMS, CSL-Behring, Merck, Otsuka, Novartis and Novo-Nordisk , Mitsubishi Tanabe Pharma Corporation, Sanofi, Research Support; Boehringer Ingelheim-Lilly, Merck, Janssen, Sanofi, AstraZeneca and Novo-Nordisk. F.Cosentino: Advisory Panel; Merck Sharp & Dohme Corp., Pfizer Inc., Speaker's Bureau; AstraZeneca, Boehringer Ingelheim International GmbH, Bristol-Myers Squibb Company, Lilly, Merck Sharp & Dohme Corp., Novo Nordisk. D.K.Mcguire: Consultant; AstraZeneca, Boehringer Ingelheim International GmbH, CSL Behring, ESPERION Therapeutics, Inc., Lexicon Pharmaceuticals, Inc., Lilly, Merck & Co., Inc., Novo Nordisk, Pfizer Inc., Sanofi. J.Liu: Employee; Merck & Co., Inc. C.Liu: Employee; Merck & Co., Inc., Stock/Shareholder; Merck & Co., Inc. R.Frederich: Employee; Pfizer Inc., Stock/Shareholder; Bristol-Myers Squibb Company, Pfizer Inc. J.P.Mancuso: Employee; Pfizer Inc., Stock/Shareholder; Pfizer Inc. Funding This study was sponsored by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, and Pfizer Inc., New York, NY, USA.

859-P: Effects of Ertugliflozin on Uric Acid and Gout-Related Outcomes: Post Hoc Analyses from VERTIS CV

The effect of ertugliflozin (ERTU) on serum uric acid (SUA) and gout-related outcomes in VERTIS CV (NCT01986881) was investigated. Patients with T2D and ASCVD were randomized to ERTU 5 mg (n=2752) , 15 mg (n=2747) (doses pooled for analyses) , placebo (PBO; n=2747) . Changes in SUA and composite of gout onset or initiation of anti-gout medication were assessed. LSM changes from baseline in SUA (mg/dL [95% CI]) at week 260 were −0. (−0.25, −0.13) and 0. (−0.02, 0.15) in the ERTU and PBO groups, respectively, nominal P<0.0 (Fig. 1) . The HR (95% CI) for the composite of gout-related outcomes was 0.76 (0.580, 1.002) , nominal P=0.052 (Fig. 2) . Treatment with ERTU was associated with reductions from baseline in SUA and a non-significant reduction in gout-related outcome events compared with PBO. Disclosure V.S.Sridhar: None. D.Cherney: Other Relationship; AbbVie Inc., AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Janssen Research & Development, LLC, Lilly, Maze, BMS, CSL-Behring, Merck, Otsuka, Novartis and Novo-Nordisk , Mitsubishi Tanabe Pharma Corporation, Sanofi, Research Support; Boehringer Ingelheim-Lilly, Merck, Janssen, Sanofi, AstraZeneca and Novo-Nordisk. F.Cosentino: Advisory Panel; Merck Sharp & Dohme Corp., Pfizer Inc., Speaker's Bureau; AstraZeneca, Boehringer Ingelheim International GmbH, Bristol-Myers Squibb Company, Lilly, Merck Sharp & Dohme Corp., Novo Nordisk. S.Dagogo-jack: Consultant; AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Janssen Pharmaceuticals, Inc., Medtronic, Merck & Co., Inc., Sanofi. R.E.Pratley: Other Relationship; Bayer AG, Corcept Therapeutics, Dexcom, Inc., Hanmi Pharm. Co., Ltd., Merck & Co., Inc., Metavention, Novo Nordisk, Pfizer Inc., Poxel SA, Sanofi, Scohia Pharma Inc., Sun Pharmaceutical Industries Ltd. R.Frederich: Employee; Pfizer Inc., Stock/Shareholder; Bristol-Myers Squibb Company, Pfizer Inc. M.N.Essex: Employee; Pfizer Inc., Stock/Shareholder; Pfizer Inc. M.Maldonado: Employee; Merck & Co., Inc. C.Liu: Employee; Merck & Co., Inc., Stock/Shareholder; Merck & Co., Inc. J.P.Mancuso: Employee; Pfizer Inc., Stock/Shareholder; Pfizer Inc. Funding The VERTIS CV study and this analysis were sponsored by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, and Pfizer Inc., New York, NY, USA.

32-OR: The Advancing Care for T1D Obesity Network (ACT1ON) Sequential Multiple Assignment Randomized Trial Pilot Re-randomization Results

Background: Sequential Multiple Assignment Randomized Trials (SMARTs) efficiently address practical treatment comparison questions and adapt dynamically based on response. They may be useful for development of approaches to co-manage weight and glycemia T1D, which is critical yet challenging. Methods: Our SMART pilot with three diet periods enrolled young adults with T1D (BMI 27-39.9 kg/m²) . Participants were re-randomized after ∼3 months on the hypocaloric Look AHEAD (Low Fat) or Low Carbohydrate (Low Carb) ; or Mediterranean (Med, not calorie restricted) diet if <2% weight was lost, HbA1c increased ≥0.5%, diet was unacceptable, or hypoglycemia increased. We present descriptive statistics for weight, HbA1c, and re-randomization for diet period 1 pre-COVID before shifting to a virtual protocol. Results: The proportion re-randomized was 57.9% and did not vary by diet. Weight was lost overall but insufficient weight loss was the most common reason for re-randomization for Low Fat and Med. An HbA1c increase ≥0.5% was most common on Med. Low diet acceptability was the most common reason for re-randomization on Low Carb. Conclusions: We achieved safe weight loss among young adults with T1D but observed heterogeneity in reasons for re-randomization by diet, although differences were not statistically significant. A fully-powered efficacy trial may confirm our findings. Disclosure D.Igudesman: None. R.E.Pratley: Other Relationship; Bayer AG, Corcept Therapeutics, Dexcom, Inc., Hanmi Pharm. Co., Ltd., Merck & Co., Inc., Metavention, Novo Nordisk, Pfizer Inc., Poxel SA, Sanofi, Scohia Pharma Inc., Sun Pharmaceutical Industries Ltd. M.R.Kosorok: n/a. D.M.Maahs: Advisory Panel; Abbott Diabetes, Eli Lilly and Company, Medtronic, Novo Nordisk, Sanofi, Consultant; Aditx Therapeutics, Inc., Biospex. E.J.Mayer-davis: None. J.Crandell: n/a. T.Pokaprakarn: None. K.Corbin: None. D.P.Zaharieva: Research Support; Insulet Corporation, International Society for Pediatric and Adolescent Diabetes, Leona M. and Harry B. Helmsley Charitable Trust. A.Addala: None. J.Thomas: None. A.Casu: None. M.Riddell: Advisory Panel; Zealand Pharma A/S, Zucara Therapeutics, Consultant; Eli Lilly and Company, Jaeb Center for Health Research, Speaker's Bureau; Dexcom, Inc., Eli Lilly and Company, Novo Nordisk. Funding National Institutes of Health 1DP3DK113358

1281-P: Understanding the Interaction between Type 2 Diabetes and COVID-via Extracellular Vesicle Proteomic and Phosphoproteomic Signatures

Evidence supporting the involvement of EVs in the pathogenesis/severity of SARS-CoV-2 infection is starting to accumulate. However, little is known about their specific associations in the context of COVID-and type 2 diabetes interaction. Our study included 48 plasma samples (N=12/group) obtained from COVID-patients with and without diabetes and from patients with non-COVID-acute respiratory diagnosis (RSP) with and without diabetes. Participants were identified from a set of 494 patients hospitalized at AdventHealth in June-August 2020. Important efforts were made to ensure the homogeneity of the study cohort. Patients with type 1 diabetes, or pregnant, or that went directly into the ICU were excluded, and 4 balanced groups were identified after 10,000 random cohorts were generated and differences in age, gender, race, and ethnicity statistically assessed. EVs were isolated using EVTRAP (Tymora) . Mass spectrometry-based methods were used to detect the global EV proteome and phosphoproteome. Differentially expressed features, enriched pathways, and enriched tissue-specific protein sets were identified. Multidimensional scaling of all EV proteomic and phosphoproteomic data and unsupervised clustering of differentially expressed (absolute fold change ≥ 2, P < 0.05, FDR < 0.05) EV proteins and phosphoproteins successfully distinguished the 4 study groups with close to 100% accuracy. Importantly, we detected enriched pathway networks that suggest the potential therapeutic utility of PKC inhibitors such as bisindolylmaleimide IX, sotrastaurin, and enzastaumn, and inhibitors of ROCK1 such the isoquinoline derivative Fasudil. In conclusion, we characterized the proteomic landscape of the interaction between type 2 diabetes and COVID-and defined disease-specific EV proteomic signatures that provide insight into the disease pathobiology and druggable targets with potential clinical utility. Disclosure Y.O.Nunez lopez: None. A.Iliuk: None. A.Casu: None. D.S.Lupu: None. R.E.Pratley: Other Relationship; Bayer AG, Corcept Therapeutics, Dexcom, Inc., Hanmi Pharm. Co., Ltd., Merck & Co., Inc., Metavention, Novo Nordisk, Pfizer Inc., Poxel SA, Sanofi, Scohia Pharma Inc., Sun Pharmaceutical Industries Ltd.

744-P: Effects of a Novel Long-Acting GIP/GLP-1/Glucagon Trireceptor Agonist, HISHS-3001, on HbA1c, Body Weight, and Lipid Metabolism

HISHS-30is a novel long-acting, Gastric inhibitory peptide (GIP) /Glucagon like peptide-1 (GLP-1) /Glucagon tri-receptor agonist. An in-vitro cyclic AMP assay in human receptor- expressing CHO-K1 cells demonstrated that HISHS-30had a half-maximal effective concentration 2.9 and 6.5 fold higher than exendin-4 or GIP, respectively, and 355-fold lower than glucagon. Subcutaneous dosing every third day for 4 weeks in diabetic db/db mice of HISHS-30at 3 and 20 nmol/kg reduced HbA1c, body weight, triglycerides and glucagon levels robustly and markedly more than tirzepatide (Table) .Treatment with HISHS-30also led to an increase in serum and liver Fibroblast Growth Factor-21 (FGF-21) levels vs. tirzepatide. In conclusion, HISHS-30is a potent, long acting GIP/GLP-1/glucagon tri-receptor agonist, with higher effects on glucose homeostasis and metabolic biomarkers in diabetic mice than tirzepatide. Disclosure V.S. Burade: None. A. Garcia-Ocana: Consultant; Sun Pharmaceutical Industries Ltd. R.E. Pratley: Other Relationship; Bayer AG, Corcept Therapeutics, Dexcom, Inc., Hanmi Pharm. Co., Ltd., Merck & Co., Inc., Metavention, Novo Nordisk, Pfizer Inc., Poxel SA, Sanofi, Scohia Pharma Inc., Sun Pharmaceutical Industries Ltd. G.A. Rutter: Advisory Panel; Sun Pharmaceutical Industries Ltd. Research Support; Sun Pharmaceutical Industries Ltd. T. Vilsbøll: Consultant; AstraZeneca, Bristol-Myers Squibb Company, Eli Lilly and Company, Gilead Sciences, Inc., GlaxoSmithKline plc., Merck Sharp & Dohme Corp., Mundipharma, Novo Nordisk, Sun Pharmaceutical Industries Ltd. B. Thorens: Advisory Panel; Sun Pharmaceutical Industries Ltd., The Healthy Aging Company.

743-P: Effect of Once-Weekly TZP on Glycemic Control by Baseline Age in Patient Subpopulations from the SURPASS Trials

Tirzepatide (TZP) is a dual GIP and GLP-1 receptor agonist developed for the treatment of patients with type 2 diabetes (T2D) . The SURPASS clinical trials demonstrated efficacy and safety of TZP 5, 10, and 15 mg, administered once weekly in patients with T2D. This post-hoc analysis of the 5 SURPASS studies was undertaken to assess the efficacy of TZP in subgroups of subjects <65 years and ≥65 years of age. Prespecified subgroup analyses were conducted on the mITT population in all 5 global Phase 3 trials to assess the effects of treatment (TZP vs. placebo or active comparator) on change from baseline in HbA1c. End of treatment HbA1c was evaluated at week 40 or 52. Efficacy estimands, based on data collected from participants on treatment and without rescue medication, were utilized for all analyses reported here. For all 5 studies, analyses of change from baseline in HbA1c at 40 or 52 weeks for both age subgroups were consistent with the primary study results, with the treatment differences favoring all 3 doses of TZP compared with placebo (SURPASS-1 and -5) or active comparator (SURPASS-2, -3 and -4) (Figure) . The most frequent adverse events with TZP were mild-to-moderate, gastrointestinal-related and occurred during the dose-escalation period. In all 5 trials and for subjects in both prespecified age subgroups, TZP demonstrated significantly greater reductions in HbA1c versus placebo or active comparator. Disclosure C.H.Wysham: Research Support; Abbott, Corcept Therapeutics, Eli Lilly and Company, Mylan N.V., Novo Nordisk. S.Tofe: Advisory Panel; Lilly Diabetes, Novo Nordisk, Research Support; Lilly Diabetes, Novo Nordisk, Speaker's Bureau; Lilly Diabetes, Novo Nordisk. H.Sapin: Employee; Eli Lilly and Company. R.Malik: None. L.M.Neff: Employee; Eli Lilly and Company, Research Support; Amryt Pharma Plc, Novo Nordisk, Stock/Shareholder; Eli Lilly and Company.

481-P: Eligibility for Icosapent Ethyl in Patients with Type 2 Diabetes and Atherosclerotic Cardiovascular Disease: An Analysis of VERTIS CV

Among patients with type 2 diabetes (T2D) treated with statins, residual cardiovascular (CV) risk remains. Because icosapent ethyl (IPE) has been shown to decrease CV risk in patients on statin therapy, we explored potential eligibility for IPE therapy in VERTIS CV (NCT01986881) , the CV outcomes trial of ertugliflozin in which all patients had T2D and atherosclerotic CV disease (ASCVD) . We analyzed eligibility for IPE based on REDUCE-IT trial inclusion criteria (on statin, fasting triglyceride of 135 to 499 mg/dL and low-density lipoprotein cholesterol of 41 to 100 mg/dL) . Among 8246 patients randomized, the mean age was 64 years and 30% were female. At baseline, 6747 (81.8%) patients used statins, while 293 (3.6%) used ezetimibe, 389 (4.7%) used fish oil, and 8 (0.1%) used IPE. The REDUCE-IT trial inclusion criteria were met by 2444 (29.6%) patients at baseline and an additional 2500 (30.3%) did not fully meet the criteria but had baseline triglyceride level >135 mg/dL (Figure) . In conclusion, this analysis of the VERTIS CV trial population identified important opportunities to reduce residual CV risk: consideration of adding statin therapy in 18% of patients and of adding IPE based on the REDUCE-IT trial inclusion criteria or triglyceride level threshold in 60% of patients. These findings highlight the need to optimize lipid therapies in patients with T2D and ASCVD. Disclosure J.M.Kim: Other Relationship; Pfizer Inc. R.Frederich: Employee; Pfizer Inc., Stock/Shareholder; Bristol-Myers Squibb Company, Pfizer Inc. J.P.Mancuso: Employee; Pfizer Inc., Stock/Shareholder; Pfizer Inc. C.P.Cannon: Advisory Panel; Alnylam Pharmaceuticals, Inc., Amarin Corporation, Amgen Inc., Amryt Pharma Plc, Applied Therapeutics, Ascendis Pharma A/S, Boehringer Ingelheim International GmbH, Bristol-Myers Squibb Company, Eli Lilly and Company, Janssen Pharmaceuticals, Inc., Lexicon Pharmaceuticals, Inc., Merck & Co., Inc., Pfizer Inc., Rhoshan, Sanofi, Research Support; Amgen Inc., Better Therapeutics, Boehringer Ingelheim International GmbH, Bristol-Myers Squibb Company, Daiichi Sankyo, Janssen Pharmaceuticals, Inc., Merck & Co., Inc., Novo Nordisk, Pfizer Inc. D.L.Bhatt: Research Support; Afimmune Limited, Amarin Corporation, Amgen Inc., AstraZeneca, Boehringer Ingelheim International GmbH, Chiesi USA, Inc., Lexicon Pharmaceuticals, Inc., Lilly, Novartis AG, Sanofi. S.Dagogo-jack: Consultant; AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Janssen Pharmaceuticals, Inc., Medtronic, Merck & Co., Inc., Sanofi. D.Cherney: Other Relationship; AbbVie Inc., AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Janssen Research & Development, LLC, Lilly, Maze, BMS, CSL-Behring, Merck, Otsuka, Novartis and Novo-Nordisk , Mitsubishi Tanabe Pharma Corporation, Sanofi, Research Support; Boehringer Ingelheim-Lilly, Merck, Janssen, Sanofi, AstraZeneca and Novo-Nordisk. F.Cosentino: Advisory Panel; Merck Sharp & Dohme Corp., Pfizer Inc., Speaker's Bureau; AstraZeneca, Boehringer Ingelheim International GmbH, Bristol-Myers Squibb Company, Lilly, Merck Sharp & Dohme Corp., Novo Nordisk. D.K.Mcguire: Consultant; AstraZeneca, Boehringer Ingelheim International GmbH, CSL Behring, ESPERION Therapeutics, Inc., Lexicon Pharmaceuticals, Inc., Lilly, Merck & Co., Inc., Novo Nordisk, Pfizer Inc., Sanofi. R.E.Pratley: Other Relationship; Bayer AG, Corcept Therapeutics, Dexcom, Inc., Hanmi Pharm. Co., Ltd., Merck & Co., Inc., Metavention, Novo Nordisk, Pfizer Inc., Poxel SA, Sanofi, Scohia Pharma Inc., Sun Pharmaceutical Industries Ltd. C.Liu: Employee; Merck & Co., Inc., Stock/Shareholder; Merck & Co., Inc. N.B.Cater: Employee; Pfizer Inc., Stock/Shareholder; Pfizer Inc. Funding Merck Sharp & Dohme Corp.

558-P: Effect of Vitamin D Supplementation on Regression to Normal Glucose Regulation from Prediabetes in the D2d Study

Regression to normal glucose regulation (NGR) has been reported in response to lifestyle modification and medications. In this secondary analysis of the D2d study, a randomized trial of 4,000 IU/d of vitamin D3 vs. placebo, we determined whether vitamin D increased regression to NGR in people with prediabetes. Eligible participants met at least 2-of-3 ADA glycemic criteria for prediabetes (n=2423) and the two groups were similar at baseline. During follow-up, glycemic status was assessed semi-annually with FG and HbA1c and annually with 2-hour glucose after 75-g glucose load (2hPG) . In exploratory analyses that censored follow up at initiation of diabetes/weight-loss medication, stopping trial pills, taking vitamin D above the trial limit, death or withdrawal, we tested for an effect of vitamin D on new-onset NGR, which was defined as the first occurrence of 2 or 3 glycemic criteria in the normal range and none in the diabetes range. Over a median follow-up of 2.5 years, the NGR outcome occurred in 343/12 participants in the vitamin D group and 295/1212 in the placebo group; hazard ratio (95%CI) for time-to-NGR for vitamin D was 1.16 (0.99-1.36) . Among those who never met NGR during follow-up (n=1785) , 29% developed diabetes compared to 8.2% among those who met NGR at some point during the study (p<0.01) . At the last encounter, the NGR outcome was observed in 133/1069 participants in the vitamin D group and 102/1050 in the placebo group; incidence rate ratio (95%CI) for vitamin D was 1.26 (0.97-1.63) . When we used the NGR definition from other studies to include only those with normal FG and 2hPG regardless of HbA1c, 90/1037 participants in the vitamin D group and 63/1050 in the placebo group at the last encounter had NGR; incidence rate ratio (95%CI) for vitamin D 1.39 (1.01-1.91) . In conclusion, vitamin D supplementation increased the likelihood of regression to NGR at the last visit, and those who met NGR during the study were less likely to subsequently develop diabetes. Disclosure D.S.Hsia: None. A.G.Pittas: None. D2d research group: n/a. J.P.Nelson: None. E.Vickery: None. N.Rasouli: Advisory Panel; Eli Lilly and Company, Novo Nordisk, Sanofi, Research Support; Allergan, Eli Lilly and Company, Novo Nordisk. E.S.Leblanc: n/a. S.H.Kim: Advisory Panel; GI Dynamics, Consultant; Aligos, Research Support; Fractyl Health, Inc. I.Brodsky: None. R.E.Pratley: Other Relationship; Bayer AG, Corcept Therapeutics, Dexcom, Inc., Hanmi Pharm. Co., Ltd., Merck & Co., Inc., Metavention, Novo Nordisk, Pfizer Inc., Poxel SA, Sanofi, Scohia Pharma Inc., Sun Pharmaceutical Industries Ltd. B.Dawson-hughes: None. Funding American Diabetes Association (1-14-D2d-01) ; National Institutes of Health National Institute of Diabetes and Digestive and Kidney Diseases and Office of Dietary Supplements (U01DK098245)

747-P: Baseline Characteristics of Subjects in the Once-Weekly (OW) Semaglutide FLOW Kidney Outcomes Trial

Chronic kidney disease (CKD) is a common complication of type 2 diabetes (T2D) that increases the risk of kidney failure and cardiovascular (CV) disease. Data from CV outcomes trials suggest that glucagon-like peptide-1 receptor agonists have kidney-protective effects. The FLOW trial (NCT03819153) will evaluate kidney outcomes with OW semaglutide in subjects with T2D and CKD. FLOW is an ongoing randomized, double-blinded, multinational, phase 3b trial. Subjects (N=3,535) with T2D, estimated glomerular filtration rate (eGFR) ≥25-≤75 mL/min/1.73 m2, and urine albumin-to-creatinine ratio >100-<5,000 mg/g were assigned 1:1 to OW semaglutide 1.0 mg or placebo, plus standard-of-care. The primary endpoint is time to first occurrence of kidney failure (as measured by persistent eGFR <15 mL/min/1.73 2 or initiation of chronic dialysis or kidney transplantation) ; ≥50% persistent eGFR reduction compared with baseline; kidney or CV death. At baseline, 68.6% of subjects had HbA1c >7.0%, diabetes complications were common, and 15.5% were taking a sodium-glucose co-transporter-2 inhibitor (Table) . The majority of subjects (68.2%) were at very high risk for CKD progression (Kidney Disease: Improving Global Outcomes criteria) . Subjects enrolled in FLOW had substantial diabetes burden and risk for CKD progression. FLOW will assess kidney outcomes with OW semaglutide in this population. Disclosure R.E.Pratley: Other Relationship; Bayer AG, Corcept Therapeutics, Dexcom, Inc., Hanmi Pharm. Co., Ltd., Merck & Co., Inc., Metavention, Novo Nordisk, Pfizer Inc., Poxel SA, Sanofi, Scohia Pharma Inc., Sun Pharmaceutical Industries Ltd. V.Perkovic: Advisory Panel; Astellas Pharma Inc., Baxter, DURECT Corporation, Merck & Co., Inc., Metavant Sciences, Mundipharma, Relypsa Inc., Other Relationship; AbbVie Inc., AstraZeneca, Bayer AG, Bristol-Myers Squibb Company, Dimerix, Eli Lilly and Company, Eli Lilly and Company, Gilead Sciences, Inc., GlaxoSmithKline plc., Janssen Research & Development, LLC, Mitsubishi Tanabe Pharma Corporation, Novartis Pharma K.K., Novo Nordisk, Novo Nordisk, Otsuka America Pharmaceutical, Inc., Pfizer Inc., Sanofi, Servier Laboratories, Tricida, Inc., UpToDate. F.M.M.Baeres: Employee; Novo Nordisk, Stock/Shareholder; Novo Nordisk. G.Bakris: Consultant; Alnylam Pharmaceuticals, Inc., AstraZeneca, DiaMedica Therapeutics, Inc., Horizon Therapeutics plc, Ionis Pharmaceuticals, Merck & Co., Inc., Other Relationship; Novo Nordisk. J.Lawson: Employee; Novo Nordisk A/S. K.W.Mahaffey: Consultant; Novo Nordisk. J.F.Mann: Advisory Panel; AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Novo Nordisk A/S. H.Mersebach: Employee; Novo Nordisk A/S. P.Rossing: Consultant; Astellas Pharma Inc., AstraZeneca, Bayer AG, Gilead Sciences, Inc., Merck Sharp & Dohme Corp., Novo Nordisk A/S, Sanofi, Speaker's Bureau; Eli Lilly and Company. K.R.Tuttle: Advisory Panel; Boehringer Ingelheim International GmbH, Gilead Sciences, Inc., Consultant; AstraZeneca, Eli Lilly and Company, Research Support; Bayer AG, Goldfinch Bio, Inc., Novo Nordisk, Travere.

Glucocorticoid receptor antagonism promotes apoptosis in solid tumor cells.

Background: Resistance to antiproliferative chemotherapies remains a significant challenge in the care of patients with solid tumors. Glucocorticoids, including endogenous cortisol, have been shown to induce pro-survival pathways in epithelial tumor cells. While pro-apoptotic effects of glucocorticoid receptor (GR) antagonism have been demonstrated under select conditions, the breadth and nature of these effects have not been fully established.Materials and Methods: To guide studies in cancer patients, relacorilant, an investigational selective GR modulator (SGRM) that antagonizes cortisol activity, was assessed in various tumor types, with multiple cytotoxic combination partners, and in the presence of physiological cortisol concentrations.Results: In the MIA PaCa-2 cell line, paclitaxel-driven apoptosis was blunted by cortisol and restored by relacorilant. In the OVCAR5 cell line, relacorilant improved the efficacy of paclitaxel and the potency of platinum agents. A screen to identify optimal combination partners for relacorilant showed that microtubule-targeted agents consistently benefited from combination with relacorilant. These findings were confirmed in xenograft models, including MIA PaCa-2, HeLa, and a cholangiocarcinoma patient-derived xenograft. In vivo, tumor-cell apoptosis was increased when relacorilant was added to paclitaxel in multiple models.Conclusions: These observations support recently reported findings of clinical benefit when relacorilant is added to paclitaxel-containing therapy in patients with ovarian and pancreatic cancers and provide a new rationale for combining relacorilant with additional cytotoxic agents.

643-P: A Model-Based Evaluation of Glycemic and Weight Changes When Switching from Semaglutide to Additional Doses of Dulaglutide

Dulaglutide 3.0 and 4.5 mg subcutaneous (SC) once weekly (QW) doses are approved for glycemic control in patients with type 2 diabetes (T2D). Using pharmacokinetic/pharmacodynamic models built from and validated with published data from SUSTAIN 1 to 10 trials for SC semaglutide and patient-level data from AWARD-11 for dulaglutide, simulations were used to predict the glycated hemoglobin (A1c) and bodyweight effects of switching from semaglutide 0.5 mg or 1.0 mg QW to 3.0 mg or 4.5 mg dulaglutide. Simulations of 100 trials with 100 virtual patients with T2D per scenario were generated by a sampling with replacement method from the AWARD-11 study dataset, which compared 3.0 and 4.5 mg dulaglutide doses to 1.5 mg as an add-on to metformin in 1842 patients with T2D with a mean baseline age of 57 years, weight of 96 kg and A1c of 8.6%. In the simulations, semaglutide was initiated at 0.25 mg for 4 weeks per approved label, and 52-week time-course predictions were conducted for changes from baseline (CFB) in mean A1c and body weight for semaglutide 0.5 mg QW or 1.0 mg QW for 26 weeks, followed by a switch to dulaglutide 0.75 mg QW or 1.5 mg QW and dose-escalated every 4 weeks to 3.0 mg QW or 4.5 mg QW, for the remaining 26 weeks. At 26 weeks, model-predicted CFB mean A1c and weight for 0.5 mg semaglutide were -1.5 % and -3.4 kg, and at 52 weeks, after switching to 3.0 mg dulaglutide dosed with escalation for 26 weeks, these were -1.7 % and -4.8 kg, respectively. Model-predicted mean A1c and weight CFB for 1.0 mg semaglutide after 26 weeks were -1.8 % and -4.9 kg, and at 52 weeks, after switching to 4.5 mg dulaglutide with dose escalation, these values were -1.8 % and -5.4 kg, respectively. In conclusion, switching from semaglutide 0.5 mg QW to dulaglutide 3.0 mg QW and from 1 mg semaglutide QW to dulaglutide 4.5 mg QW predicted additional and comparable CFB A1c, respectively, but with greater weight loss for both modeled scenarios. Disclosure L. Tham: Employee; Self; Eli Lilly and Company. K. M. Pantalone: Consultant; Self; AstraZeneca, Bayer Inc., Corcept Therapeutics, Eli Lilly and Company, Merck & Co., Inc., Novo Nordisk Inc., Research Support; Self; Bayer Inc., Merck & Co., Inc., Novo Nordisk, Speaker’s Bureau; Self; AstraZeneca, Merck & Co., Inc., Novo Nordisk. K. M. Dungan: Advisory Panel; Self; Eli Lilly and Company, Tolerion, Inc., Consultant; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Elsevier, Novo Nordisk, Other Relationship; Self; UpToDate, Research Support; Self; Abbott, Sanofi-Aventis, Viacyte, Inc. K. M. Munir: None. C. Tang: Employee; Self; Eli Lilly and Company, Employee; Spouse/Partner; Novartis AG. M. Konig: Employee; Self; Eli Lilly and Company. A. Kwan: Employee; Self; Eli Lilly and Company, Employee; Spouse/Partner; Eli Lilly and Company, Stock/Shareholder; Self; Eli Lilly and Company, Stock/Shareholder; Spouse/Partner; Eli Lilly and Company.

Brolucizumab vs aflibercept and ranibizumab for neovascular age-related macular degeneration: a cost-effectiveness analysis.

BACKGROUND: Age-related macular degeneration (AMD) is a leading cause of blindness worldwide and is the most common cause of blindness in developed countries. Despite antivascular endothelial growth factor (anti-VEGF) therapy demonstrating improvements in visual and anatomical outcomes, unmet needs remain. Brolucizumab-dbll (ie, brolucizumab), a VEGF inhibitor for treatment of neovascular (wet) AMD and recently approved by the FDA for its treatment of wet AMD, attempts to mitigate treatment burden through less frequent injections. OBJECTIVE: To assess the incremental cost-effectiveness of brolucizumab compared with aflibercept and ranibizumab, given similar costs per injection and the potential for longer dosing intervals based on phase 3 clinical trial data. METHODS: A Markov model was developed to model the treatment of wet AMD patients with brolucizumab vs aflibercept and vs ranibizumab over a lifetime time horizon (base case) and 5-year time horizon (scenario analysis). The Markov model consisted of 3 primary health states: on treatment, off treatment, and death. Markov substates (5 total) described visual acuity (VA) ranging from no vision impairment to blindness. These VA-based substates were defined by best-corrected visual acuity (BCVA) values measured using Early Treatment Diabetic Retinopathy Study letters. Fixed-dosing regimens for each therapy were included in the model: dosing every 4 weeks (q4w) for the first 3 months followed by dosing q8w/q12w for brolucizumab, dosing q4w for the first 3 months followed by dosing q8w for aflibercept, and q4w for ranibizumab. RESULTS: In the base case, brolucizumab was less costly than aflibercept ($63,614 vs $72,189), and brolucizumab generated 0.0079 more quality-adjusted life-years (QALYs) than aflibercept (4.580 vs 4.572). Lower total costs with brolucizumab were driven by reduced drug costs ($56,432 vs $64,057), reduced administration costs ($6,013 vs $6,825), and reduced monitoring costs ($1,168 vs $1,306). When evaluating the cost-effectiveness of brolucizumab over a 5-year time horizon, brolucizumab was less costly than aflibercept ($44,644 vs $50,772) and generated an additional 0.0049 QALYs (2.953 vs 2.948). Additionally, brolucizumab was less costly than ranibizumab ($63,614 vs $128,163) and generated 0.0078 more QALYs than ranibizumab (4.580 vs 4.572) in the base case. Lower total costs with brolucizumab were driven by reduced drug costs ($56,432 vs $114,516), reduced administration costs ($6,013 vs $11,541), and reduced monitoring costs ($1,168 vs $2,107). When evaluating the cost-effectiveness of brolucizumab over a 5-year time horizon, brolucizumab was less costly than ranibizumab ($44,644 vs $89,665), and brolucizumab generated an additional 0.0046 QALYs (2.953 vs 2.948). CONCLUSIONS: Brolucizumab can be cost saving and cost-effective compared with aflibercept and ranibizumab in the treatment of wet AMD. DISCLOSURES: Novartis Pharmaceuticals Corporation provided funding to Xcenda for the cost-effectiveness analysis and preparation of this manuscript. Carlton is an employee of Xcenda. Agashivala is employed by Novartis Pharmaceuticals Corporation; Yu was an employee of Novartis Pharmaceutical Corporation at the time of this study. Hassan reports personal fees from iOPEN, BVI/Visitrec, ArcticDx, Bayer, F. Hoffmann-La Roche Ltd, Broadspot, BMC, Katalyst Surgical, Alcon, Vitreq, Surgicube, personal Ocugenix, Regeneron, Allergan, Oculus Surgical, Novartis, Genentech, and Eyepoint, unrelated to this work. Wykoff reports personal fees from Corcept Therapeutics, DORC, EyePoint, Gyroscope, IVERIC Bio, Merck, Notal Vision, ONL Therapeutics, Oxurion, Palatin, PolyPhotonix, Takeda, Thea Open Innovation; grants from Aerie Pharmaceuticals, Aldeyra, Gemini Therapeutics, Graybug Vision, IONIS Pharmaceutical, LMRI, Mylan, Neurotech Pharmaceuticals, Outlook Pharmaceuticals, Samsung Bioepis, Senju, Taiwan Liposome Company, Xbrane BioPharma, Santen; and grants and personal fees from Adverum, Allergan, Apellis, Chengdu Kanghong Biotechnologies (KHB), Clearside Biomedical, Genentech, Kodiak Sciences, NGM Biopharmaceuticals, Novartis, Opthea, Recens Medical, Regenxbio, Roche, and Regeneron, unrelated to this work. This research was presented as a virtual poster at the AMCP 2020 Annual Meeting, April 2020.

Abstract #977113: Use of Mifepristone in a Hypercortisolemic Patient with End Stage Renal Disease on Hemodialysis

There is currently no published data on the use of mifepristone (Korlym®, Corcept Therapeutics) in patients with End Stage Renal Disease (ESRD) on hemodialysis diagnosed with hypercortisolism. We present a patient case with ESRD demonstrating the safe and efficacious long-term use of mifepristone.

The Effect of a Novel Glucocorticoid Receptor Antagonist (CORT113176) on Glucocorticoid and Insulin Receptor Sensitive Hepatic Gene (mRNA) Expression in a Neonatal Rat Model of Human Prematurity

Preterm birth is a global health problem the sequelae of which are not well understood. Hypoxia, a common stressor with prematurity, can affect blood glucose via stress-induced increases in glucocorticoids (GC). GCs are also administered to preterm infants to improve oxygenation; however, this is controversial. CORT113176 (Corcept Therapeutics) is a novel, selective glucocorticoid receptor (GR) antagonist that does not bind to the progesterone receptor. We have demonstrated that CORT113176 (in our rat model of preterm birth) increases baseline corticosterone (due to loss of GC negative feedback) and attenuates hypoxia-induced increases in insulin resistance implicating endogenous corticosterone in post-natal metabolic adaptations to stress. We now propose that CORT113176 is useful to evaluate the hepatic effects of endogenous GCs in our rat model of preterm birth by measuring critical GC and insulin receptor sensitive gene mRNAs. Postnatal day (PD) 2 rat pups of both sexes (N=5 per treatment/sex) were pretreated with CORT113176 (600 mg/kg IP) or vehicle. After 60 minutes, a group of pups were euthanized with livers collected and preserved in RNAlater (baseline). The remaining pups were separated from their dams, exposed to normoxia (control) or hypoxia (8% O2) for 60 minutes, and livers obtained. Total hepatic RNA was extracted, and mRNA expression was analyzed (RT-qPCR) for GC and insulin receptor sensitive genes: GC: Fkbp5, Gilz, Nr3c1 (Gr), Nr3c2 (Mr), Per1, Ttpa. INSULIN: Akt2, G6Pase, Igf1r, Insr, Irs1, Irs2, Pik3cb, Pik3r1, Srebp1c. CORT113176 decreased the expression of all baseline hepatic insulin receptor mRNAs in both sexes, except for G6Pase. Pik3r1 mRNA expression significantly decreased with 60 minutes of normoxic separation (fasting) in males and females compared to baseline and hypoxic separation; this was blocked by CORT113176. In the GC receptor sensitive panel, CORT113176 decreased basal Nr3c1 (Gr) mRNA. Normoxic and hypoxic separation increased Per1 and Gilz mRNA expression; this effect was blocked by CORT113176. Interestingly, Fkbp5 expression, a proposed clinical marker for GR antagonism, was not altered by CORT113176. The hepatic GC and insulin receptor sensitive gene mRNA panels we developed are sensitive to GR antagonism suggesting they may be a useful addition to Fkbp5. The increase in endogenous corticosterone, acting via GR, is critical in the hepatic response to stress in our neonatal rat model of hypoxia and prematurity.

Relacorilant With Pembrolizumab: A Phase 1b, Open-Label Study of a Selective Glucocorticoid Receptor Modulator Combined With a Checkpoint Inhibitor for Patients With Adrenocortical Carcinoma With Excess Glucocorticoid Production

Adrenocortical carcinoma (ACC) is an aggressive cancer with poor response to chemotherapeutic and immunotherapeutic agents. About half of ACCs produce glucocorticoids (GC), and the presence of GC excess (hypercortisolism) is correlated with decreased survival in patients with ACC. The broad immunosuppressive effects of GC may contribute to the limited efficacy of immune checkpoint inhibitors, such as pembrolizumab, in these patients.Antagonism of the glucocorticoid receptor (GR) has the potential to increase immune-related transcripts, thus promoting tumor immune response in ACC with GC excess. To test this hypothesis, we introduce a phase 1b study evaluating the combined treatment of relacorilant (CORT125134, Corcept Therapeutics) with pembrolizumab in patients with advanced ACC and hypercortisolism (NCT04373265). Relacorilant is a selective (no activity at other steroid receptors), oral GR modulator in development for Cushing syndrome and, in combination with chemotherapy, for various solid tumors. In healthy subjects, prednisone causes rapid reductions in eosinophils, lymphocytes, and osteocalcin and rapid increases in neutrophils. Relacorilant ameliorates these effects. In a phase 2 study in patients with endogenous Cushing syndrome treated with relacorilant, improvements in the signs and symptoms of GC excess were seen.The primary objective of this study is to determine the safety and efficacy of the recommended regimen of relacorilant with pembrolizumab in patients with advanced ACC and hypercortisolism. Pembrolizumab infusion will occur on day 1 of each 21-day cycle, and relacorilant will be administered once daily, starting 3 days before the first pembrolizumab infusion. Relacorilant doses will be escalated in 100-mg increments (100 mg up to 400 mg, as tolerated). Patients will receive treatment until they experience disease progression or unacceptable toxicity.Approximately 20 adults with confirmed advanced, unresectable and/or metastatic ACC will be enrolled. GC excess must be documented by either ACTH <10 pg/mL and serum cortisol >1.8 µg/dL after dexamethasone suppression testing (DST), or the presence of two of the following criteria: elevated urinary free cortisol; high late-night salivary cortisol; and DST cortisol >1.8 µg/dL.Assessments will include safety, tolerability, and efficacy. Secondary objectives include a determination of the non-progression rate at 27 weeks, evaluation of progression-free survival, overall survival, duration of response, and an assessment of the effect of the combination on clinical manifestations of hypercortisolism.This will be the first clinical study to evaluate whether GR antagonism promotes tumor response in patients with ACC and GC excess treated with checkpoint inhibitors.

COVID-19 and Cushing's syndrome: recommendations for a special population with endogenous glucocorticoid excess

COVID-19 and Cushing's syndrome: recommendations for a special population with endogenous glucocorticoid excess

1201-P: Impact of a Nursing Strike on Glycemic Control of Hospitalized Patients with Diabetes

Introduction: Inpatient maintenance of glycemic control relies heavily on nurse-directed care. In July 2018, our academic medical center experienced a nursing strike. Replacement staff were employed during the strike. The purpose of this study was to investigate the impact of a disrupted nursing workforce on glycemic control of hospitalized patients with diabetes. Methods: This was a retrospective cohort study of glycemic control during a nursing strike. Data included three, 48-hour periods: pre-strike, strike, and post-strike. All adult hospitalized patients with diabetes were eligible. Patients were excluded if they were in the intensive care unit. The primary outcome was the frequency of hyperglycemia, defined as average percentage of point-of-care finger stick tests &amp;gt; 180 mg/dL per patient. Hypoglycemia was defined as average percentage of tests &amp;lt; 70 mg/dL per patient. Data were analyzed using Wilcoxon rank sum tests with P&amp;lt;0.05 considered statistically significant. Results: Two hundred and eleven patients were included in the analysis: 65 patients (30.8%) in the strike period and 146 patients (69.2%) during the comparative periods. There were no differences in age, sex, race, or body mass index between groups. During the strike period, a mean of 35.5% of patients’ glucose tests met criteria for hyperglycemia, versus a mean of 31.2% of tests in the comparative periods (P=0.46). A mean of 1.4% of glucose tests met criteria for hypoglycemia during the strike period, versus a mean of 0.2% during normal operations (P=0.02). Conclusions: Hyperglycemia did not vary significantly with a short-term disruption in nursing workforce. There was a suggestion of increased hypoglycemia, however this was a rare event and should be interpreted with caution. Disclosure K. Sheahan: None. B. Tompkins: None. A.G. Kennedy: None. A.B. Repp: None. M.P. Gilbert: Advisory Panel; Self; Corcept Therapeutics. Consultant; Self; Novo Nordisk Inc.

LBA3 - VELIA/GOG-3005: Integration of veliparib (V) with front-line chemotherapy and maintenance in women with high-grade serous carcinoma of ovarian, fallopian tube, or primary peritoneal origin (HGSC)

LBA3 - VELIA/GOG-3005: Integration of veliparib (V) with front-line chemotherapy and maintenance in women with high-grade serous carcinoma of ovarian, fallopian tube, or primary peritoneal origin (HGSC)