bluuebunny/crossref_metadata_2025_split huggingface dataset:
875-P: Association of Continued Sodium–Glucose Cotransporter-2 Inhibitors from the Ambulatory to Inpatient Setting with In-Hospital Outcomes in Patients with Diabetes Mellitus—A Nationwide Study
Authors: SINGH LAKSHMI G. , NTELIS SPYRIDON , SIDDIQUI TARIQ , SELIGER STEPHEN L. , SORKIN JOHN D. , (ELIAS) SPANAKIS ILIAS 
Published: June 2023

Objective: Limited data are available on continuation of outpatient sodium glucose co-transporter-2 inhibitors (SGLT2i) during hospitalization.
Design: Nationwide study of admissions of veterans with diabetes where SGLT2i was continued (CONT) in the hospital (N=5,943) compared to those where it was discontinued (DC) (N=30,634). Primary outcome was in-hospital mortality. Secondary outcomes were acute kidney injury (AKI), intensive care unit (ICU) transfer and length of stay (LOS). Propensity-weighted Poisson regression analyses adjusted for age, sex, race, BMI, Elixhauser comorbidity index were performed.
Results: Mean (SE) age was 67.2 (0.1) and 67.5 (0.1) years (p=0.03), male 97.0% and 96.6% (p=0.1), white 71.3% and 72.1%, black 20.8% and 20.5% (p=0.52) in CONT vs. DC groups, respectively. After covariate adjustment, CONT had 44% lower mortality rate (IRR 0.56, 95% CI 0.43, 0.74, p=0.0001), no difference in AKI (IRR 0.95, 95% CI 0.89, 1.01, p=0.12), and 41% lower rate of ICU transfer (IRR 0.59, 95% CI 0.53, 0.65, p&lt;0.0001). LOS was 4.5 vs. 4.9 days (IRR 0.93, 95% CI 0.91, 0.95, p&lt;0.0001), in the CONT vs. DC. Similar trends observed after adjusting for additional models.
Conclusion: Continued SGLT2i during hospitalization was associated with lower mortality and ICU transfer, no increased AKI, and shorter LOS.

Disclosure
L.G.Singh: None. S.Ntelis: None. T.Siddiqui: None. S.L.Seliger: Other Relationship; Tricida, Inc., Research Support; Reata Pharmaceuticals, Inc., Palladio Bioscences, Roche Diagnostics. J.D.Sorkin: None. I.Spanakis: Research Support; Dexcom, Inc.
889-P: Effectiveness of Dapagliflozin as Add-on to Metformin Alone or Metformin with Other Oral Antidiabetic Drug Classes in Type 2 Diabetes Mellitus—A Multicentre, Retrospective, Real-World Evidence Study
Authors: SETHI BIPIN , SAHAY RAKESH K. , TIWASKAR MANGESH H. , DHEDIYA RAJNISH , GAURAV KUMAR , RATHOD RAHUL T. , KOTAK BHAVESH P. , DHANAKI GAURI D. , SHAH SNEHAL 
Published: June 2023

Background: Present real-world study evaluated the effectiveness of dapagliflozin as an add-on modality, in adult patients with T2DM.
Method: We conducted an EMR-based retrospective, multicentre study in adult T2DM patients inadequately controlled on existing antidiabetic therapy and receiving dapagliflozin as add-on therapy. Baseline characteristics (visit 1) and treatment-related outcomes (visit 2 considered between 60 days-140 days after adding dapagliflozin) which included HbA1C, BMI, SBP & DBP were analyzed.
Results: 3616 patients were included from 478 centres, of which 55.7% were males. Mean age was 51 years (range: 40-64 years). Most patients had received dapagliflozin + metformin + at least one other OAD [D+M+OAD, n=2907 (80.4%), 408 followed-up], while 709 patients (19.6%, 138 followed-up) received dapagliflozin + metformin (D+M). For D+M group, significant mean change was noted for all parameters at follow-up except SBP and DBP (non-significant reductions for HbA1c ≥ 8% subgroup). For D+M+OAD group, significant change was noted for all parameters at follow-up except BMI (non-significant reduction). (Table 1)
Conclusion: Dapagliflozin showed significant improvement in glycemic parameter, BMI and BP when added to metformin, with or without other OADs in real-world.

Disclosure
B.Sethi: None. R.K.Sahay: Advisory Panel; Torrent Pharmaceuticals Ltd, Speaker's Bureau; Novo Nordisk A/S, USV Private Limited, Intas Pharmaceuticals Ltd., Eris Lifesciences Ltd. M.H.Tiwaskar: None. R.Dhediya: None. K.Gaurav: None. R.T.Rathod: None. B.P.Kotak: Employee; Dr. Reddy's Laboratories Ltd. G.D.Dhanaki: None. S.Shah: None.

Funding
Dr. Reddy’s Laboratories, Ltd.
892-P: Influence of Preceding Medications on the Renal Outcomes of Japanese Diabetics Treated with SGLT2 Inhibitors and GLP-1 Receptor Agonists
Authors: KOBAYASHI KAZUO , TOYODA MASAO 
Published: June 2023

Background/Objective: Evidence of cardiovascular and renal outcomes has already been shown for SGLT2 inhibitors (SGLT2i) and GLP1 receptor agonists (GLP1Ras); therefore, combination therapy with these drugs is of clinical interest. This study aimed to evaluate the effect of the preceding drug for patients with the combination treatment of SGLT2i and GLP1Ra on renal outcomes.
Methods: We retrospectively extracted data of patients with type 2 diabetes mellitus who had received both SGLT2i and GLP1Ra treatment for at least 1-year at 18 medical facilities in Japan. Finally, 341 patients in the GLP1Ra-preceding group and 319 in the SGLT2i-preceding group were analyzed. The renal composite outcome was progression of the albuminuria stage, ≥30% decrease in eGFR, or both. The multiple imputation method for missing values and an inverse probability weighting method using the propensity score were used for the comparison of outcome.
Results: The median observation period and the incidence of the renal composite outcome in the SGLT2i-preceding group and the GLP1Ra-preceding group was 55.1months, 26.9% and 58.7months, 25.6%, respectively, with an odds ratio (OR) [95% confidence interval] of 1.50 [0.89, 2.53] (p=0.13). The ORs for the ≥30% decrease in eGFR and the progression of albuminuria stage were 0.96 [0.47, 2.00] (p=0.93) and 1.76 [0.97, 3.69] (p=0.06), respectively. Compared to the GLP1Ra-preceding group, the annual change in eGFR and change in the logarithmic value of urine albumin-to-creatinine ratio (LnACR) was 0.27mL/min/1.73 m2/year [-0.60, 1.14], and 0.18 [-0.10, 0.43] respectively. LnACR at baseline, pioglitazone use, and baseline mean arterial blood pressure were independent factors for renal composite outcome with ORs [95% CI] of 1.15 [1.01, 1.31], 0.47 [0.23, 0.96], and 1.03 [1.01, 1.05], respectively.
Conclusion: In combination therapy with SGLT2i and GLP1Ra, the difference in the preceding drug did not affect the renal composite outcome.

Disclosure
K.Kobayashi: None. M.Toyoda: None.
893-P: Relation between Combination Therapy with SGLT2 Inhibitors and GLP-1 Receptor Agonists and Renal Functions among Japanese Diabetics
Authors: TOYODA MASAO , KOBAYASHI KAZUO 
Published: June 2023

Background/Objective: SGLT2 inhibitors (SGLT2i) and GLP1 receptor agonists (GLP1Ra) have already shown evidence of cardiovascular and renal outcomes; therefore, combination therapy with these drugs is now of interest in clinical practice for the management of type 2 diabetes mellitus (T2DM). However, there are few reports on the effect of combination therapy on renal functions. This study aimed to investigate the effect of combination therapy on renal functions.
Methods: We retrospectively extracted data of patients with T2DM who had received both SGLT2i and GLP1Ra treatment for at least 1-year at 18 medical facilities in Japan. Finally, 341 patients in the GLP1Ra-preceding group and 319 in the SGLT2i-preceding group were analyzed. The multiple imputation method was adopted for missing values, and propensity score (PS) matching with the algorithm of 1:1, neighbor match, and no replacement, was performed for comparison between the two groups.
Result: In each group, 152 patients were matched. On the matched model, mean observational period was 54 months. Regarding the annual change in eGFR (mL/min/m2/year) before and after combination treatment, the SGLT2i-preceding group showed a significant increase from -3.76±10.48 to 0.04±6.29 (p=0.002), whereas the GLP1Ra-preceding group showed no significant change from -2.09±13.44 to -1.97±6.16. The logarithmic value of urine albumin-to-creatinine ratio at the time of the initiation of either drug, at the time of the initiation of combination treatment, and after the combination treatment, were 3.77±1.63, 3.83±2.21, 3.73±1.80 in GLP1Ra-preceding group, and 3.65±20.4, 3.56±1.29, 3.75±0.91 in SGLT2i-preceding group, respectively, and there was no significant difference among two groups. Conclusion: The addition of GLP1Ra to SGLT2i-treated patients significantly improved the annual change in eGFR. The renal benefits by combination therapy with SGLT2i and GLP1Ra may be affected by preceding drug.

Disclosure
M.Toyoda: None. K.Kobayashi: None.
895-P: Effect of Long-Term Empagliflozin Therapy on Plasma Beta-Hydroxy Butyrate (ß-OHB)—Lack of Effect of Concomitant Insulin, GLP-1 Agonist, or Pioglitazone Therapy
Authors: ORTIZ LUIS C. , WORTHAM JOY , PINKSON SHEILA , TREJO JONATHAN , MENDOZA AMIEL S. , CHEN XI , TRIPATHY DEVJIT 
Published: June 2023

Sodium-glucose transporter 2 (SGLT2) inhibitors are associated with increased risk of euglycemic diabetic ketoacidosis in T2DM. Possible mechanisms include increased lipolysis, elevated glucagon, and decreased plasma insulin levels. Therefore, concomitant high dose insulin as well as thiazolidinediones could potentially attenuate the rise in β-OHB because of anti-lipolytic effects. However, this has not been examined in the real-world clinical studies. We examined the effect of long-term Empagliflozin therapy on plasma β-OHB in veterans with T2DM. A retrospective chart review was performed in 43 subjects who had fasting β-OHB, C-peptide and detailed anthropometric measurements and were followed for 23 ± 2.5 months. Subjects were categorized into two groups based on fasting β-OHB concentrations (&lt; or ≥2.8mg/dl). Eleven patients (24.4%) had high (6.03 ±1.22mg/dl) while 32 (74.6%) had normal β-OHB (1.42±0.09 mg/dL). There was no difference in age (59 ± 4 vs 62 ±2 yrs), BMI (35±1 vs 32 ±1 kg/m2), or the duration of diabetes (15 ± 3 vs 18±2 yrs) between the two groups. Subjects with higher β-OHB had higher HbA1c (8.9 ±0.7 vs 7.9 ± 0.3%, p&lt;0.05). There was no difference in fasting C-peptide (3.2 ± 0.9 vs 3.5 ± 0.5ng/ml), total daily insulin dose (184± 43 vs 214±19 units/day), number of subjects on Pioglitazone (54 vs 35%) or GLP-1 agonist therapy (36 vs 52%) between the two groups. In conclusion, long-term therapy with Empagliflozin leads to elevated β-OHB in 25% of T2DM and it was associated with poor glycemic control. Concomitant insulin or pioglitazone therapy did not alter plasma β-OHB concentration.

Disclosure
L.C.Ortiz: None. J.Wortham: None. S.Pinkson: None. J.Trejo: None. A.S.Mendoza: None. X.Chen: None. D.Tripathy: None.
896-P: Effectiveness of Newly Prescribed SGLT2 Inhibitors as Second-Line Therapy following DPP-4 Inhibitors or Metformin as First-Line Therapy in Type 2 Diabetes Patients
Authors: TAKAHASHI HIROSHI , SUGANUMA YUKA , OHNO TAKAYUKI , NISHIMURA RIMEI 
Published: June 2023

Prescriptions of SGLT2 inhibitors (SGLT2i) for patients with type 2 diabetes (T2DM) are increasing. In this study real-world data were used to evaluate the long-term benefits of SGLT2i as a second-line drug for glycemic control in people with T2DM being treated with DPP-4 inhibitor (DPP4i) or metformin (MET) monotherapy. People with T2DM patients on DPP4i or MET monotherapy were followed for at least 12 months after receiving a new SGLT2i prescription. Patients were divided into DPP4i and MET groups, and patient background factors were controlled for using propensity score matching (PM). Changes in HbA1c and other indexes during the 12 months after the new prescription were compared using t-tests, and the factors affecting changes in HbA1c were examined using multiple regression analysis. After PM, there were 192 patients in the DPP4i (n=96) and MET (n=96) groups, with no significant differences in patient backgrounds. HbA1c levels 12 months after a new SGLT2i prescription were significantly lower in both groups compared to base line (8.1% to 7.0%, p&lt;0.001; 8.1% to 7.1%, p&lt;0.001), but there were no significant differences between the two groups in the change in HbA1c level (p=0.271), body weight (p=0.371), systolic blood pressure (p=0.828), eGFR (p=0.642), and Fib-4 index (p=0.674). The change in HbA1c was greater for those with initially higher HbA1c levels (-0.629 [-0.722-0.536], p&lt;0.001) and those with shorter diabetes histories (0.024 [0.001-0.048], p=0.044), but it was not significantly different between the two groups (p=0.236). After controlling for patient background, there was no significant difference in the long-term effects of a new SGLT2i prescription between those previously receiving either DPP4i or MET monotherapy, but higher previous HbA1c levels and a shorter diabetes history may be prediction of better HbA1c 12 months after a new SGLT2i prescription, regardless of prior medication.

Disclosure
H.Takahashi: Speaker's Bureau; Eli Lilly Japan K.K., Boehringer Ingelheim Japan, Inc., Medtronic, Novo Nordisk. Y.Suganuma: None. T.Ohno: None. R.Nishimura: Speaker's Bureau; Sanofi K.K., Medicure Inc., Boehringer Ingelheim Inc., Takeda Pharmaceutical Company Limited, Kissei Pharmaceutical Co., Ltd., Novartis Pharma K.K., Eli Lilly Japan K.K., Novo Nordisk, Merck & Co., Inc., Abbott Japan Co., Ltd., Astellas Pharma Inc., Teijin Pharma Limited, Taisho Pharmaceutical Holdings Co., Ltd., Ono Pharmaceutical Co., Ltd., AstraZeneca.
898-P: Real-World Glycemic Outcomes of &gt;3,300 Children and Adolescents with Type 1 Diabetes Using the Omnipod 5 Automated Insulin Delivery (AID) System with Cloud-Based Data Management
Authors: SHERR JENNIFER , DESALVO DANIEL , HUYETT LAUREN M. , SNOW KENNETH , MENDEZ JOSE J. , HADJIYIANNI IRENE , LY TRANG T. 
Published: June 2023

The Omnipod 5 AID System is a novel tubeless hybrid closed-loop system that allows for personalized therapy through customizable glucose targets from 110-150mg/dL in 10mg/dL increments. The System enables automatic upload of data for all users initiating the system, facilitating unprecedented access to evaluate real-world outcomes. Continuous glucose monitoring (CGM) and insulin data from Omnipod 5 users with type 1 diabetes (T1D) aged &lt;18y in the US with ≥90 days of data available in the cloud-based data management system were included. Data from 3,369 users with sufficient CGM data (≥75% of days with ≥220 readings) and using the lowest target (110mg/dL) for ≥50% of the time, aged &lt;6y (n=182), 6 to 12y (n=2,050), and 13 to 17y (n=1,137) were available at the time of analysis. Users were aged mean±SD 10.9±3.4y with median 146 days of system use. Outcomes are shown in the Table for each age group. Median time in target range (70-180mg/dL) was 74.0%, 70.7%, and 67.1% for each age group, respectively. Time &lt;70mg/dL in each age group was low: median 2.7%, 1.8%, and 1.2%, respectively. These results are the first to demonstrate that in over 3,000 children and adolescents using the Omnipod 5 System in a real-world setting, highly favorable glycemic outcomes are achievable and are similar to those first reported in pivotal trials.

Disclosure
J.Sherr: Advisory Panel; Bigfoot Biomedical, Inc., Insulet Corporation, Medtronic, Vertex Pharmaceuticals Incorporated, Cecelia Health, StartUp Health T1D Moonshot, Consultant; Bigfoot Biomedical, Inc., Insulet Corporation, Medtronic, Lilly, Research Support; Insulet Corporation, Medtronic, NIH - National Institutes of Health, Juvenile Diabetes Research Foundation (JDRF), Speaker's Bureau; Insulet Corporation, Zealand Pharma A/S, Lilly, Medtronic. D.Desalvo: Consultant; Dexcom, Inc., Research Support; Insulet Corporation. L.M.Huyett: Employee; Insulet Corporation, Stock/Shareholder; Insulet Corporation. K.Snow: Employee; Insulet Corporation. J.J.Mendez: None. I.Hadjiyianni: Employee; Insulet Corporation, Stock/Shareholder; Insulet Corporation, Eli Lilly and Company. T.T.Ly: Employee; Insulet Corporation.

Funding
Insulet Corporation
90-LB: Real-World Effectiveness of an Oral Superabsorbent Hydrogel for Weight Management
Authors: BIALONCZYK DAMIAN , ZHOU MEGAN S. , BROFFMAN LAUREN , DORON TZVI Y. , BOWLES JENNIFER , CHIQUETTE ELAINE 
Published: June 2023

Background and Objective: Plenity is a non-systemic oral superabsorbent hydrogel which promotes fullness by increasing the volume and elasticity of ingested food in the stomach and small intestine. The efficacy and safety of the oral hydrogel have been demonstrated in clinical trials. This study evaluated weight change in people with overweight or obesity following treatment with the oral hydrogel in a real-world setting.
Research Design and Methods: Data was analyzed using chart records from a national telehealth platform. Demographic and health information and anthropometric measures were self-reported by patients during online visits. Patients were included in the analysis if they had received a prescription for the oral hydrogel, had a follow-up visit at 180 ± 30 days, reported having access to treatment for ≥ 75% of days, and reported taking it at least 1 day per week. Descriptive statistical analysis and tests of differences (χ2, t-tests) were performed in R Version 4.2.2.
Results: Patients (n=894) were 74% female, aged 50 ± 11 years, with a mean pre-treatment body weight of 90 ± 16 kg and BMI of 32.0 ± 4.1 kg/m2. One-third (35%) of patients had overweight (BMI 25-30 kg/m2) at baseline and mean treatment duration was 160 ± 16 days. Weight loss of any amount (&gt;0 kg) was reported by 85.9% of patients, with a mean weight change of -6.1 ± 3.9% (-5.6 ± 3.8 kg) in this group. About half (48%) of all patients achieved clinically significant weight loss of ≥ 5%. Among these treatment responders, mean weight loss was 8.7 ± 3.3% (8.0 ± 3.4 kg). Clinically significant weight loss response ≥ 5% was more likely among people that reported poor baseline diet quality (P = 0.02).
Conclusions: Treatment with an oral superabsorbent hydrogel in people with overweight and mild obesity in a real-world environment was associated with clinically significant weight loss response at 6 months. People with self-assessed poor baseline diet quality, in particular, were more likely to have a meaningful response to therapy.

Disclosure
D. Bialonczyk: Employee; Gelesis. M. S. Zhou: Employee; Ro. L. Broffman: Employee; Roman Health Adventures. T. Y. Doron: Employee; Roman Health Adventures. J. Bowles: Employee; MCPHS University, Gelesis. E. Chiquette: Consultant; Gelesis.
902-P: Patient Experience and Clinical Outcomes in Pregnant Patients with Type 1 Diabetes Using Open-Source Automated Insulin Dosing Systems
Authors: YANG YIFAN , HALPERIN ILANA 
Published: June 2023

Type 1 diabetes (T1D) in pregnancy is associated with increased obstetrical and neonatal complications; thus, stringent glycemic targets are imperative. While commercial automated insulin dosing (AID) systems represent an important development in management of T1D, a limitation is that the glycemic targets are not adjustable for pregnancy. Before commercial AID, a community of people with T1D combined CGM sensors, insulin pumps and open-source code, developing open-source automated insulin delivery systems (OSAIDS). Given customizable glycemic targets, OSAIDS may fill an important clinical gap in pregnancy. We included participants ≥18 years old with T1D who had at least one pregnancy using OSAIDS. Of 37 completed surveys, motivations for using OSAIDS included commercial AID targets being too high for pregnancy (78%), increased ownership over diabetes (53%) and transparency (44%). The INsulin Dosing Systems: Perceptions, Ideas, Reflections and Expectations (INSPIRE) questionnaire showed that 100% strongly agreed or agreed with: helped in pregnancy (89% strongly agree), better quality of life (94% strongly agree) and better sleep (83% strongly agree). With a glycemic target of 3.5-7.8mmol/L (63-140mg/dl), 86% exceeded the time-in-range (TIR) target of ≥ 70% set by the Advanced Technologies & Treatments for Diabetes Congress. The majority (66%) had a more stringent TIR of ≥ 80%. The vast majority (97%) did not have severe hypoglycemia; 74% had time-below-range ≤ 4%. Of the 71% who experienced labor and delivery, 90% delivered at 37 weeks gestational age or greater; 90% did not have shoulder dystocia. Median birth weight was 3374g (SD 600g), 19% of newborns had macrosomia (&gt;4000g). Neonatal hypoglycemia (&lt;2.5mmol/L/&lt;45mg/dl) occurred in 24% with 14% requiring NICU. OSAIDS provides excellent glycemic control, maternal quality of life and neonatal outcomes. More data is needed to validate these initial promising outcomes.

Disclosure
Y.Yang: None. I.Halperin: Advisory Panel; Sanofi, Speaker's Bureau; 3Boehringer Ingelheim Canada Ltd./Ltée, Abbott Diabetes, Dexcom, Inc., Novo Nordisk.
903-P: Correlation of Gene Expression and Cellular Pathways in Insulin-Expressing Mouse Liver Cells Transduced with an Integrating Adeno-associated Viral Vector (AAV)
Authors: JOSHUA SERGIO , NASSIF NAJAH T. , SIMPSON ANN M. 
Published: June 2023

Gene therapy is being considered as a treatment/cure for type 1 diabetes (T1D). Previously we used a clinically-applicable AAV to deliver furin cleavable insulin (INS-FUR) to the livers of diabetic non-obese diabetic mice. The traditional AAV8 that allows predominantly episomal expression, and the hybrid AAV8/piggyBac that results in transgene integration into the host genome were used. Euglycaemia was achieved in mice (n=4) that received AAV8/piggyBac-INS-FUR, but not in mice that received AAV8-INS-FUR. In the current study global transcriptomic profiling was carried out, by total RNA sequencing, to compare the key pathways modulated in hepatocytes that reversed diabetes with those that did not. Using Qiagen CLC Workbench, significant genes were identified based on fold change expression cut offs of, and a false discovery rate p-value of &lt;0.05. Selected genes were mapped onto the various cellular pathways using Qiagen Ingenuity Pathway Analysis (IPA) software to determine trends in pathway activation/ inactivation related to the altered gene expression. IPA analysis showed that the canonical pathways identified between the treatments remained largely the same, however their downstream biological processes differed. Key canonical pathways identified include pathways related to insulin signalling, glucose and lipid metabolism. Key pathway players identified as significantly altered in the comparative treatments included insulin, major histocompatibility complex class I, A, glucose-6-phosphatase catalytic subunit 1 and insulin like growth factor binding protein 1. The profile of AAV8/piggyBac-INS-FUR transduced mouse livers resembled that of a normal liver compared to livers transduced with AAV8-INS-FUR. This study confirms the correlation of transcriptomic data mapping and has identified differences in the cellular effects of both vector systems used to deliver INS-FUR for T1D treatment.

Disclosure
S.Joshua: None. N.T.Nassif: None. A.M.Simpson: None.

Funding
National Health and Medical Research Council of Australia (1086256)