bluuebunny/crossref_metadata_2025_split huggingface dataset:
653-P: Evaluating Antidiabetic Medication Treatment Patterns in T2D Patients Initiating Once-Weekly Semaglutide (sema OW)
Authors: WILLEY VINCENT , SHIVAPPA NITIN , SWIFT CAROLINE , NOONE JOSHUA , DU SIMO , PAPROCKI YUREK M. , TAN HIANGKIAT (JASON) 
Published: June 2021

Antidiabetic medication (med) treatment patterns often differ based on a variety of patient and prescriber factors. Understanding these patterns may provide insight on optimizing therapy, especially when considering initiation of a new therapy. This study presents real-world evidence on T2D treatment patterns associated with sema OW initiation within a large cohort of T2D patients.
Methods: Claims and lab result data were used to identify T2D patients from a US commercially insured/Medicare Advantage population who initiated sema OW between 12/1/17 - 6/30/20 (index as 1st claim). Selected patients had continuous health plan enrollment for ≥ 2 years pre-index and post-index through at least 90 days after the last available A1c value. Antidiabetic meds prescribed before, at the time and after initiation of sema OW were evaluated overall and for those with an A1c &gt;9%.
Results: A total of 3,081 T2D patients were identified, of which 865 patients had A1c &gt;9%. Sema OW was initiated down the treatment pathway, with ~60% on ≥2 and ~30% on 3+ T2D meds at sema OW initiation. Sema OW was an add-on therapy to most T2D med classes overall, although when initiated onto more complex therapy regimens it was more likely to be a therapy switch (T2D monotherapy = 24% switched to sema OW, dual therapy = 46%, triple therapy = 64%, 4+ T2D medications = 70%). Following post-index A1c measurement, 35% of patients overall and 29% with a baseline A1c &gt;9% decreased the number of their T2D meds.
Conclusion: Sema OW appeared to be initiated as add-on therapy, except for those on more complex regimens. Approximately 1/3 of patients decreased their overall T2D med use after evaluation of A1c following sema OW initiation. Further research is warranted to assess impact of initiating sema OW earlier in the T2D treatment pathway, especially in patients with cardiovascular and chronic kidney disease.

Disclosure
V. Willey: Employee; Self; HealthCore. N. Shivappa: Other Relationship; Self; Novo Nordisk. C. Swift: Employee; Self; Novo Nordisk Inc. J. Noone: Employee; Self; Novo Nordisk Inc. S. Du: None. Y. M. Paprocki: Employee; Self; Novo Nordisk, Stock/Shareholder; Self; Novo Nordisk. H. Tan: Other Relationship; Self; HealthCore.
74-LB: Sudden Changes in Interstitial Glucose Sensing by Remote Real-Time Continuous Glucose Monitoring as a Marker of Hypoperfusion in Critically-Ill Patients with COVID-19
Authors: HESTER JOI , DAVIS GEORGIA M. , PASQUEL FRANCISCO J. , RABINOVICH MARINA , POINDEXTER NORMA , TEKWANI SEEMA 
Published: June 2021

Introduction: During the COVID-19 pandemic, we implemented a protocol combining continuous glucose monitoring (CGM) with a computerized intravenous insulin infusion algorithm to care for patients with severe COVID-19.
Objective: To examine glucose trends surrounding cardiac arrest events to evaluate the performance of CGM sensors during severe clinical instability.
Methods: We reviewed eight cases of patients with type 2 diabetes diagnosed with COVID-19 requiring ICU care on IV insulin and CGM therapy experiencing severe clinical decompensation leading to cardiac arrest. Index events (cardiac arrest) were identified by staff documentation in the electronic health record. Clinical characteristics, mean arterial pressure (MAP), and point-of-care (POC) glucose values surrounding the index event were collected. CGM data was paired with MAP and POC glucose values. Rapid declines in the glucose trend [rate of change (ROC) ≥3mg/dl/min] were identified during this time of clinical instability.
Results: The mean age of patients was 61.3±13.8 years. All patients were treated with steroid therapy, vasopressors, and mechanical ventilation. 62.5% were on CRRT. Four (50%) patients had sudden cardiac arrest and drop in MAP, while the other four patients had a more prolonged decline in MAP prior to cardiac arrest. CGM values in those with sudden arrest showed an abrupt decline (≥3mg/dl/min) an average of 16.7±13.7 min following cardiac arrest. Rapid down trending of CGM values in those with prolonged hypotension occurred on average about 6 hours prior to cardiac arrest. During these episodes, the CGM values stopped correlating with POC tests.
Conclusions: Real-time CGM in critically-ill patients may provide clinical information beyond glucose control. Rapid declines in CGM values (≥3mg/dl/min) not correlating with POC glucose testing are associated with both sudden and prolonged changes in arterial pressure.

Disclosure
J. Hester: None. G. M. Davis: None. F. J. Pasquel: Consultant; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Research Support; Self; Dexcom, Inc., Merck & Co., Inc. M. Rabinovich: None. N. Poindexter: None. S. Tekwani: None.
75-LB: Can Continuous Glucose Monitoring Be Utilized to Monitor Adherence to Time-Limited Eating in Adolescents with Obesity?
Authors: NAGUIB MONICA , GORAN MICHAEL I. , RAYMOND JENNIFER , HEGEDUS ELIZABETH , WEE CHOO PHEI , VIDMAR ALAINA 
Published: June 2021

Background: One limitation to studying time limited eating (TLE) in adolescents is difficulty in reliably assessing adherence to fasting periods. Dietary recalls, which are currently used to monitor diet adherence, have been criticized due to potential error in reporting, omission bias and suboptimal compliance. Continuous glucose monitoring (CGM) may be a useful tool to overcome these barriers; however, it requires daily wear and understanding of expected glycemic excursions. The present study examines the feasibility of daily CGM use and its utility as a tool to monitor adherence to fasting periods in a diverse cohort of adolescents with obesity participating in a pilot study of 8-hour TLE.
Methods: Twenty adolescents (mean age 16.0+1.3 years, 70% female, 55% Latinx, 75% public insurance) with BMI ≥ 95th percentile, were enrolled in a 12-week study and randomized to: (1) Group 1 (control schedule): 12-hour eating period + blinded CGM, (2) Group 2 (TLE schedule): 8-hour eating period + blinded CGM, or (3) Group 3: 8-hour eating period + CGM with real-time feedback. CGM wear time was calculated as the actual weekly wear time divided by the prescribed wear time. At weeks 0, 4 and 12, CGM data from 7 days of self-reported fasting periods were reviewed to evaluate any glycemic excursions &gt;50 ng/dL.
Results: Overall, the mean CGM wear time was 90% (35-100%) with no difference between intervention arms. During self-reported fasting periods, only 4 adolescents had excursions &gt;50 ng/dL, one of whom was diagnosed with type 2 diabetes. The remaining 16 participants had no excursions &gt;50 ng/dL during their fasting periods.
Conclusions: These data suggest that CGM may be a feasible tool to monitor adherence to TLE and provide a more accurate assessment of true fasting periods with less opportunity for error and bias when compared to self-report. Larger studies are needed to validate these findings and further explore the use of CGM as a tool in obesity research in adolescents.

Disclosure
M. Naguib: None. M. I. Goran: None. J. Raymond: None. E. Hegedus: None. C. Wee: None. A. Vidmar: None.
758-P: Treatment with Testosterone Undecanoate Injections (TU) Improves Estimated Glomerular Filtration Rate (eGFR) in Men with Hypogonadism and Type 2 Diabetes Mellitus: Update of Real-World Data
Authors: HAIDER KARIM S. , HAIDER AHMAD , SAAD FARID 
Published: June 2021

Background: Reduced eGFR is associated with increased risk of cardiovascular disease and mortality.
Methods: In a registry of 865 men with hypogonadism, 361 men (41.7%) had T2DM. 183 received TU 1000 mg every 12 weeks (T-group). 178 opted against treatment (CTRL). Changes over time between groups were compared and adjusted for age, weight, waist circumference, fasting glucose, blood pressure, lipids and quality of life to account for baseline differences between the groups. eGFR was calculated using the Modification of Diet in Renal Disease (MDRD) formula.
Results: Mean follow-up 8.7±3.1, baseline age: 61.8±5.3 years. Creatinine decreased by 0.16±0.03 mg/dL (unadjusted from 0.95±0.16 to 0.83±0.09) at 12 years in the T-group and increased by 0.33±0.03 mg/dL (1.00±0.14 to 1.26±0.42) in CTRL (p&lt;0.0001 for both). T-group: eGFR increased by 15.1±5.6 mL/min/1.73 m² (82.8±12.8 to 92.3±10.0). The peak mean value was recorded in year 9 after which a small but steady decline occurred. CTRL: eGFR decreased progressively by 22.9±5.6 mL/min/1.73 m² (77.35±13.9 to 64.4±32.5) (p&lt;0.0001 for both). Systolic blood pressure decreased in the T-group by 33.1±1.2 mmHg (163.05±13.5 to 130.23±6.5) and increased in CTRL by 18.3±1.2 mmHg (145.6±14.6 to 158.3±15.1) (p&lt;0.0001 for both). Diastolic blood pressure decreased in the T-group by 20.3±0.9 mmHg (97.4±10.9 to 75.4±3.3) and increased in CTRL by 12.5±0.9 mmHg (84.8±10.3 to 94.3±8.9) (p&lt;0.0001 for both). During the entire observation period, 15 deaths (8.3%) and no cardiovascular events occurred in the T-group. In CTRL, 61 deaths (34.3%), 56 cases of myocardial infarction (31.5%) and 56 cases of stroke (31.5%) were recorded (p&lt;0.0001 for all). Nephropathy occurred in 0.01% in the T-group and in 2.8% in CTRL (p&lt;0.05).
Conclusions: Long-term testosterone therapy in men with hypogonadism and T2DM prevents age-related deterioration in GFR.

Disclosure
K. S. Haider: Other Relationship; Self; Bayer AG. A. Haider: Other Relationship; Self; Bayer AG. F. Saad: Consultant; Self; Bayer AG, Stock/Shareholder; Self; AbbVie Inc., Bayer AG, Novo Nordisk.

Funding
Bayer AG
761-P: Safety and Pharmacokinetic Study of GPR40 Agonist (CPL207280) after a Single Dose in Healthy Subjects
Authors: BAZYDLO-GUZENDA KATARZYNA , GIERCZAK-PACHULSKA AGNIESZKA , JARUS-DZIEDZIC KATARZYNA , RUDZKI PIOTR , WIECZOREK MACIEJ 
Published: June 2021

Activation of GPR40 (G-protein coupled receptor 40) in pancreatic β-cells may improve glycaemic control in type 2 diabetes (T2D) patients through enhancement of glucose-stimulated insulin secretion (GSIS). Here we present phase I an open label, dose-escalation study with single oral administration of GPR40 agonist - CPL207280 in healthy subjects in fasting conditions. The study was performed in conventional 3+3 design, where MTD (maximum tolerated dose) is to be determined. Caucasian male and female subjects (24 volunteers) were enrolled in 8 cohorts (n=3 per). Subjects received CPL207280 in doses ranging from 5 to 480 mg. Safety assessment included adverse events (AE) reporting, clinical laboratory tests, glucose, insulin, proinsulin, c-peptide and glucagon level monitoring, vital signs, physical examination, electrocardiography (ECG). Blood samples for pharmacokinetic (PK) analysis were collected up to 48 hours after administration. CPL207280 concentrations in human plasma were evaluated by HPLC/MS/MS. Pharmacokinetic parameters were calculated using a non-compartmental modelling approach. Administration of CPL207280 was safe and well tolerated with no serious AE. All adverse events were classified as not related to the study product. Despite administration up to 480 mg of CPL207280, no dose limiting toxicity (DLT) was observed, therefore no MTD was determined. The CPL207280 exposure increased in a dose-dependent manner. The CPL207280 mean maximum plasma concentration (Cmax) values ranged from 19 to 516 ng/mL for cohort 1 and 8, respectively, and were observed at 1-3 hours after administration. The area under the curve of plasma concentration vs. time (AUC0-24h) ranged from 516 to 4603 ng/mL*h, for cohort 1 and 8, respectively. CPL207280 administration in all doses was safe and well tolerated. No adverse events were related to the study product. Pharmacokinetics of CPL207280 supports once daily dosing regimen. The results justify further clinical development.

Disclosure
K. Bazydlo-guzenda: Employee; Self; Celon Pharma SA. A. Gierczak-pachulska: Employee; Self; Celon Pharma SA. K. Jarus-dziedzic: Other Relationship; Self; Celon Pharma SA. P. Rudzki: Employee; Self; Celon Pharma SA. M. Wieczorek: Other Relationship; Self; Celon Pharma SA.

Funding
National Centre for Research and Development (POIR.01.01.01-00-0334/17)
765-P: DA-1241, a Novel GPR119 Agonist: Data on Safety, Tolerability, Pharmacokinetics (PK), and Pharmacodynamics (PD) from Part 2 of a Phase 1b Multiple Ascending Dose (MAD) Study in Patients with Type 2 Diabetes Mellitus (T2DM)
Authors: KIM MI-KYUNG , LEE DAE YOUNG , JEONG JIYOON , GRIMM MICHAEL , FRANEY BRIDGETTE B. , HOMPESCH MARCUS 
Published: June 2021

Background and Aim: DA-1241 is a novel small molecule selective GPR119 agonist. In preclinical studies DA-1241 enhanced metabolic hormones, and improved metabolic control characteristics. The primary objective of Part 2 was to assess safety and tolerability of multiple once daily oral doses of DA-1241 versus placebo and Sitagliptin in T2DM. Secondary objectives were to establish PK and PD characteristics.
Methods: Part 2 was a double blind placebo and Sitagliptin (SG) controlled study with three sequential cohorts of T2DM (n=25/cohort) blinded and randomized (3:1:1) to receive DA-1241: 25, 50 or 100 mg (n=15/cohort), placebo (n=5/cohort) or Sitagliptin (n=5/cohort) single daily oral doses for 56 days.
Results: 84 subjects were enrolled in Part 2, 3 subjects were withdrawn due to TEAEs (1 active, 2 placebo), 72 subjects completed the study. There were no relevant demographic imbalances (Age 56.8 ± 7.3, BMI 29.4 ± 3.3). Doses tested were generally safe and well tolerated. The most frequent TEAEs were mild GI side effects (nausea, diarrhea, abdominal pain), all resolved spontaneously. Day 56 PK Cmax and AUC0-tau parameters were dose proportional. Fasting plasma glucose trended towards improvement for all DA-1241 doses, as did incremental glucose exposure after MMTTs (Change from Baseline to Day 56 iAUC 0-4h: 25mg: 18.5±89.2, 50mg: -5.1±86.8, 100mg: -38.6±58.7, Placebo: 34.4±145.9, SG: -23.9±132.8) and time spent at BG &lt; 180 mg/dL. HbA1c trended towards improvement across dosing groups, as did body weight. GIP, GLP-1 and PYY were increased at day 56, consistent with the mechanism of action of DA-1241.
Conclusion: This phase 1b study in T2DM showed favorable safety, tolerability and PK profiles of DA-1241. Biomarkers and PD data confirmed the mechanism of action and showed favorable efficacy data trends.

Disclosure
M. Kim: Employee; Self; Dong-A ST Co. Ltd. D. Lee: Employee; Self; Dong-A ST Co. Ltd. J. Jeong: Employee; Self; Dong-A ST Co. Ltd. M. Grimm: None. B. B. Franey: None. M. Hompesch: Other Relationship; Self; Wiley, Stock/Shareholder; Self; ProSciento, Inc.
793-P: Dapagliflozin Improves Renal Function in Obese Indian Diabetics with Microalbuminuria
Authors: MAHAPATRA HARIBALLAV , MAHAPATRA LAXMINARAYAN , KHUNTIA MONALISA , SAHOO ABHAY K. 
Published: June 2021

SGLT2 inhibitors have gained appreciation following their acceptance as a treatment modality for people with type 2 diabetes. These agents promote glucosuia blocking the reabsorption of glucose from the proximal convoluted tubules in the kidneys. Due to the direct role on the nephrons, initially there were some concerns over their use among the renal compromised individuals. Urinary albumin to creatinine ratio (UACR) is considered as one of the indicators to access the renal function and to classify chronic kidney disease. RAAS blockers are the standard therapeutic options for reducing urinary albumin excretion among those with or without diabetes. This study aimed to find the renoprotective effect of dapagliflozin (DAPA) among obese Indian type 2 diabetics (T2D) with microalbuminuria and compared that with RAAS blockers. We considered 182 obese adults (BMI ≥30 kg/m2) with T2D and microalbuminuria for this study. Subjects were randomized into 2 groups. Those in DAPA group (n = 86, M/F: 51/35) were administered DAPA 10 mg once daily with breakfast, whereas subjects in the comparator (RAAS) arm (n = 96, M/F 54/42) were prescribed RAAS blockers (ARBs or ACE inhibitors). From comparable UACR and HbA1c at baseline, both groups witnessed a significant decline in the UACR at 12 weeks of intervention (p&lt;0.02). The change in the UACR from baseline was higher in the DAPA arm, though it was not statistically different from RAAS arm (145.7± 32.8 to 89.5 ± 35.8 mg/g vs. 131.5 ± 44.6 to 94.3 ± 28.2 mg/g). Additionally, DAPA arm in contrast to RAAS arm, proved their glycemic benefits by demonstrating a significant reduction in the HbA1c (1.5 ± 1.2% vs. 0.3 ± 0.6%). There was a drop in blood pressure in the study and comparator arms, but RAAS agents were found to be more effective in lowering blood pressure (P &lt;0.03). Dapagliflozin exhibited significant and numerically better reduction in UACR compared to RAAS blocking agents among obese microalbuminuric diabetics. Use of dapagliflozin also resulted in significant Hba1c reduction.

Disclosure
H. Mahapatra: None. L. Mahapatra: None. M. Khuntia: None. A. K. Sahoo: None.
824-P: Does Utilization of a Three-Month Multidisciplinary Endocrinology Treatment Team Improve Glycemic Control and Reduce Therapeutic Inertia in High-Risk Patients with Diabetes
Authors: IQBAL ANIRA , BROOME DAVID T. , ISAACS DIANA , RAO PRATIBHA 
Published: June 2021

Elderly patients with diabetes and poor glycemic control are at higher risk of complications. We examined the effects of utilizing a 3-month multidisciplinary team, including an endocrinologist, diabetes educator, and pharmacist, on glycemic control in order to extend specialized care and reduce therapeutic inertia in high-risk patients cared for by primary care physicians. The purpose of our study was intensification of medical management of high-risk elderly patients with diabetes through a quality improvement (QI) project with HbA1c value as the primary outcome. We identified 176 patients with diabetes in our primary care clinics who were &gt;/= 50 years old and had a HbA1C &gt;/= 9%. Of these, 22 patients were agreeable to be scheduled to follow up with a provider in our Endocrinology and Metabolism Institute as a new patient. In April 2020, baseline data was obtained (HbA1c, Albumin: Creatinine, blood pressure, BMI, lipid panel and 10-year ASCVD risk %). They were then seen by an endocrinologist and sequentially followed up by a clinical diabetes educator and a pharmacist. At the end of 12 weeks, post-intervention data was collected. Patients were then followed by their primary care physician as needed.
Results: We enrolled 22 eligible patients with type 2 diabetes in our study. The mean age was 72 +/- 7 years with a pre-study HbA1c of 9.6 +/- 1.3%, BMI of 31.0 + 5.6 kg/m2, average albumin: creatinine of 195.1 +/- 298.3 mg/g. At the end of the study, the average HbA1c value was 7.6 +/- 0.9%, and represented a 2.0% decline (95% CI 8.0-9.3, p-value &lt; 0.01). There was a 74.4 mg/g reduction in albuminuria (95% CI 61.1-282.4, p = 0.48) and a 0.5 kg/m2 increase in BMI (95% CI 29.0-33.4, p = 0.76).
Conclusion: Through use of a 3-month strategic multi-disciplinary QI initiative in high-risk patients with diabetes, we significantly improved glycemic control measured by HbA1c. A limitation of our study was the small study size.

Disclosure
A. Iqbal: None. D. T. Broome: None. D. Isaacs: Consultant; Self; InPen, Insulet Corporation, LifeScan, Speaker’s Bureau; Self; Abbott Diabetes, Dexcom, Inc., Novo Nordisk, Xeris Pharmaceuticals, Inc. P. Rao: None.
83-LB: Adherence and Persistence in Patients with T2D Initiating Once-Weekly vs. Once-Daily Injectable GLP-1RA in U.S. Clinical Practice: STAY Study
Authors: LIEBL ANDREAS , ARORA RIYA , FAURBY MADS , DA ROCHA FERNANDES JOAO DIOGO , POLONSKY WILLIAM H. 
Published: June 2021

Introduction: Reducing dosing frequency may reduce treatment burden and improve adherence and persistence. We assessed persistence and adherence in patients with T2D initiating once-weekly (OW) or once-daily (OD) injectable glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in US clinical practice.
Methods: Adults (≥ 18 years) with T2D included in the IBM MarketScan Explorys Claims-EMR Data Set for ≥ 180 days pre- and ≥ 365 days post-index, who were GLP-1 RA- and insulin-naïve at first claim for OW or OD injectable GLP-1 RA (index period: 1 Jul 2012-31 Jan 2019; follow-up: index date + 365 days), were propensity score matched 1:1 by age, sex, Charlson Comorbidity Index score, baseline HbA1c and weight (90 days pre-index), and use of sulfonylureas, metformin, DPP-4 inhibitors and SGLT-2 inhibitors (180 days pre-index). Persistence was defined as stay time (patients who had not discontinued [≥ 60 days not covered by medication] within 12 months were censored at 360 days) and assessed using Kaplan-Meier analysis and Cox proportional hazard models. Adherence was defined as proportion of days covered (PDC) ≥ 0.8.
Results: The matched cohorts (n = 784 each) had similar characteristics. Compared with OD GLP-1 RAs, OW were associated with significantly higher persistence (median stay time, 333 days vs. 269 days; hazard ratio 0.80, p &lt; 0.01) and better relative adherence at 6 months (+23%) and 12 months (+35%), irrespective of glycemic improvement and weight change. Mean HbA1c reduction was also greater for OW than for OD treatments at 6 months (-1.1% vs. -0.9%) and 12 months (-0.9% vs. -0.7%). Over 12 months, adherent patients experienced greater mean changes in HbA1c with both OW (-1.1%) and OD (-1.0%) regimens than patients with PDC &lt; 0.8 (-0.6% each).
Conclusions: Our results suggest that, in a real-world setting, OW injectable treatments are associated with better persistence and adherence than OD regimens, irrespective of glycemic or weight control.

Disclosure
A. Liebl: Advisory Panel; Self; AstraZeneca, Becton, Dickinson and Company, Boehringer Ingelheim International GmbH, Eli Lilly and Company, MSD, Novo Nordisk, Roche, Speaker’s 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. Arora: Employee; Self; Novo Nordisk. M. Faurby: Employee; Self; Novo Nordisk A/S. J. Da rocha fernandes: Employee; Self; Novo Nordisk A/S, Stock/Shareholder; Self; Novo Nordisk A/S. W. H. Polonsky: Advisory Panel; Self; Intarcia Therapeutics, Inc., Consultant; Self; Abbott Diabetes, ADOCIA, Boehringer Ingelheim Pharmaceuticals, Inc., Dexcom, Inc., Insulet Corporation, Lilly Diabetes, Novo Nordisk, Onduo LLC., Sanofi US.

Funding
Novo Nordisk A/S