bluuebunny/crossref_metadata_2025_split huggingface dataset:
803-P: How Effective Is Weight Loss by Oral Semaglutide on Glycemic Control in a Real-World Setting?
Authors: KESAVADEV JOTHYDEV , SHANKAR ARUN , JOSHI SHASHANK R. , ASHIK ASHA , YASMIN SHAHANA , BASANTH ANJANA , RAJ K SOURAV , JOTHYDEV SUNITHA 
Published: June 2024

While oral semaglutide is not approved for weight reduction, its injectable form shares which similar pharmacological properties has received FDA approval for the management of obesity. The clinical development program for oral semaglutide has shown potential benefits in body weight reduction in addition to a plethora of benefits. This real-world longitudinal study from a comprehensive diabetes centre in Kerala, India assessed the effect of weight loss on HbA1c levels in T2D using Oral Semaglutide, with follow-up data from March 2022 to July 2023 in 196 subjects. Subjects were divided into three groups based on weight loss: 0-5%, 5-10%, and over 10%. Analysis was conducted using R version 4.3.1, with a significance level set at 5%. In the cohort with a weight reduction of 0 to 5%, there was a significant HbA1c reduction of 1.13% (95% CI = 0.13 to 2.14, p = 0.032). For those who lost 5 to 10% of their weight, HbA1c decreased by 1.3% (95% CI = 0.32 to 2.28, p = 0.015). The most substantial HbA1c reduction, 1.98% (95% CI = 1.11 to 2.85, p = 0.002), was observed in the group that lost more than 10% of their weight. (Figure) This study demonstrates that oral Semaglutide effectively reduces HbA1c levels in T2DM patients, particularly in those with significant weight loss. These findings highlight its potential dual benefit in glycemic control and weight management in T2DM therapy.

Disclosure
J. Kesavadev: None. A. Shankar: None. S.R. Joshi: Consultant; Twin Health, Marico, Franco Indian, Zydus Cadila, Glenmark Pharmaceuticals. Other Relationship; Novo Nordisk, Sanofi, MSD, Abbott Nutrition, Abbott, Biocon, Alkem, USV Private Limited, Boehringer-Ingelheim. A. Ashik: None. S. Yasmin: None. A. Basanth: None. S. Raj K: None. S. Jothydev: None.
827-P: Effectiveness and Safety of Human Insulin Treatment in Elderly Patients with Type 2 Diabetes
Authors: DZIDA GRZEGORZ J. , PASTERCZYK-BIELSKA KATARZYNA , MASIEREK MALGORZATA 
Published: June 2024

Due to the progressive nature of type 2 diabetes many older people require insulin therapy. In this age group the achievement of individualized therapy goals should also include maintaining good quality of life. Avoiding hypoglycaemia is the priority. The aim of the study was to determine the distinctiveness of insulin therapy in patients aged 75 year and older when compared to those aged 65-74. The study included 1,914 T2DM patients 65 years of age and older divided into two age groups (group 1, age 65-74 and group 2, age ≥ 75 years ). The observation lasted 3 months between two visits. The analysis is part of a multicentre observational study involving 4,386 people with T2DM treated with human insulin (Gensulin). With adjustment of basal insulin dose significant reduction in A1c was achieved in both study groups. (from 8.5% to 7.8% in the group 1, and from 8.4% to 7.7% in group 2). Achievement A1C target &lt;7% in group 1 increased from 6.3% to 19.3% while target A1c ≤ 8% from 28,0% to 34.0%. In group 2 from 6% to 17,0% and from 56,9% to 81,2% consecutively. A total of 98.2% of patients in group 2 achieved their target A1c. The median daily final insulin dose was 36U in both groups. No severe hypoglycaemia episodes occured. The lack of hypoglycaemia was declared by 83.7% and 82.1% in group 1 and group 2 respectively. Improvement in compliance with recommendations in both age groups was observed, as well as increased satisfaction with the treatment used. There were no significant differences in insulin therapy between patients aged 65-74 years and ≥ 75 years. The optimalization of insulin therapy in elderly patients helps to achieve the target A1c and age over 75 years is not a limiting factor in insulin treatment.

Disclosure
G.J. Dzida: None. K. Pasterczyk-Bielska: None. M. Masierek: Employee; BIOTON.
832-P: Preferences of People with Type 2 Diabetes for Features of Weekly Insulin
Authors: GELSEY FELICIA , PEREZ-NIEVES MAGALY , VASS CAROLINE M. , LING POON JIAT , SCHAPIRO DAVID , PIERCE ANNA , MANSFIELD CAROL 
Published: June 2024

Introduction & Objective: For people with type 2 diabetes (PwT2D), daily insulin regimens can be burdensome, difficult to adhere to, and a key barrier to initiating insulin therapy. Despite developments in once-weekly basal insulins, little is known about PwT2D preferences for administration frequency or its importance relative to other insulin features.
Methods: An online discrete choice experiment survey was administered to adults with T2D in the United States. Each respondent completed 8 questions offering a choice between experimentally designed pairs of hypothetical, long-acting insulins that varied by 6 attributes: reduction in A1c level after 6 months, daily time in range, number of serious low blood sugar events, number of nighttime low blood sugar events, weight change over 6 months, and administration frequency. A fixed choice question directly elicited preferences for flexible weekly over daily insulin, holding all other attributes equal. Data were analyzed with random-parameter logits.
Results: A total of 466 people (mean: age = 57; A1c = 7.5%; 59% female) completed the survey. They were on a basal/bolus (33.3%), basal-only (34.3%), or insulin-naïve (32.4%) regimen. Relative to other attributes, people placed most importance on avoiding a 10-pound weight change, followed by the largest changes in the number of serious and nighttime low blood sugar events and achieving the longest time in range. There was significant heterogeneity in preference: insulin-naïve respondents strongly preferred weekly administration, whether on the same day each week or a flexible weekly schedule, over daily (p &lt; 0.05). In the fixed-choice question, most (67.6%) preferred flexible weekly over daily dosing.
Conclusion: Overall, the most important attributes were weight change due to insulin and number of serious hypoglycemic events. PwT2D preferred weekly over daily basal insulin when all other treatment attributes were equal. The dosing flexibility could be crucial for the insulin naïve.

Disclosure
F. Gelsey: Employee; Eli Lilly and Company. Stock/Shareholder; Eli Lilly and Company. M. Perez-Nieves: Employee; Eli Lilly and Company. Stock/Shareholder; Eli Lilly and Company. C.M. Vass: Other Relationship; Eli Lilly and Company. Consultant; National Institute for Health and Care Excellence (NICE). J. Poon: Employee; Eli Lilly and Company. Stock/Shareholder; Eli Lilly and Company. D. Schapiro: Employee; Eli Lilly and Company. A. Pierce: None. C. Mansfield: None.
843-P: Multinational Analysis of Factors Associated with Missed Bolus Insulin Injections Using Smart Pen Data
Authors: JAVIER AMPUDIA BLASCO FRANCISCO , JENSEN MAIKA L. , KAAS ANNE , KNUDSEN NIKOLINE N. , NISHIMURA RIMEI 
Published: June 2024

Introduction & Objective: Missing doses in people living with diabetes (PLWD) who use multiple daily insulin injections may lead to inadequate glycemic control. This real-world study assessed the probability of and influencing factors for missed bolus insulin injections in PLWD.
Methods: Data from 21 countries were collected from 22 964 adults with T1D or T2D using CGM and a smart pen (NovoPen 6 or NovoPen Echo Plus) to deliver bolus insulin (2 559 118 CGM and injection days [111 days/adult]). The daily probability of missing ≥ 1 bolus dose (no bolus dose within −15 to +60 mins from meal onset detected by the GRID algorithm) was estimated by a generalized linear mixed model based on logistic regression. Data upload frequency (pen to app) was used as a proxy for smart pen engagement.
Results: The mean probability of having a day with ≥ 1 missed bolus dose was 44.5% (95% CI: 44.1-45.0%), which decreased with increasing age (Figure A) and smart pen data upload frequency (not shown). The probability of having a day with ≥ 1 missed bolus dose was highest on Fridays and Saturdays (Figure B). On any given day, the probability of missing a bolus dose at breakfast, lunch, dinner or snack was 7.5%, 12.2%, 11.1% and 19.4%, respectively.
Conclusion: Bolus insulin adherence increased with age and smart pen engagement and decreased on weekends. Smart insulin pen data can provide novel insights into individuals’ real-world injection behaviors.

Disclosure
F. Ampudia Blasco: Advisory Panel; Novo Nordisk, Sanofi. Speaker's Bureau; Lilly Diabetes. Advisory Panel; Roche Diagnostics, Bayer Inc. M.L. Jensen: Employee; Novo Nordisk. A. Kaas: Employee; Novo Nordisk A/S. Stock/Shareholder; Novo Nordisk A/S. N.N. Knudsen: Employee; Novo Nordisk. Stock/Shareholder; Novo Nordisk. R. Nishimura: Speaker's Bureau; Abbott. Advisory Panel; Abbott Japan Co., Ltd. Speaker's Bureau; Boehringer-Ingelheim, Mitsubishi Tanabe Pharma Corporation, Kowa Company, Ltd., Medtronic, Sanofi, Taiho Pharmaceutical Co. Ltd., Sumitomo Dainippon Pharma Co., Ltd., Teijin Pharma Limited, Eli Lilly and Company, Novo Nordisk A/S. Consultant; Terumo Corporation.

Funding
Novo Nordisk A/S
846-P: ALP001E, a Novel Glucagon Receptor Antagonist (GRA), Improves Insulin Resistance, Glycemic Control, and ß-Cell Function in Type 2 Diabetes (T2D)
Authors: CHUNG CHENG-HO , TSENG SHI-LIANG , CHAN PO-CHAO , CASTRO GABRIEL , CHEN YEN-FU , CHEN HSU CHIA , ZEMEL MICHAEL B. 
Published: June 2024

Introduction: T2D is characterized by fasting hyperglucagonemia and inappropriate meal suppression of glucagon, resulting in increased endogenous glucose production. While GRA is an attractive T2D target, previous programs have been discontinued due to nonclinical evidence of α-cell hyperplasia and increased blood pressure, LDL, and transaminases in clinical trials. ALP001E is a novel oral GRA with no evidence of these effects in extensive animal testing. ALP001E was well-tolerated in single- and multiple-dose clinical trials, with no significant changes in blood pressure, LDL, or liver enzymes.
Objective: The objective of this trial was to assess pharmacodynamic effects of ALP001E in individuals with T2D.
Methods: A placebo-controlled, double-blind, randomized controlled trial was conducted in 20 T2D patients administered 20, 40, or 80 mg ALP001E or placebo twice daily for 14 days.
Results: Fasting glucose dose-dependently decreased 17-24% by day 2 (-1.50, -1.95, and -2.40 mmol/L for 20, 40, and 80 mg doses, p&lt;0.02) and remained suppressed throughout treatment; there was no significant change in the placebo group. Seven-point glucose dose-responsively decreased at all 7 points from baseline to day 14 for the ALP001E groups but not for placebo; the 80 mg dose group exhibited a 3.1 mmol/L (31.3%) decrease over all 7 points (p&lt;0.05). ALP001E treatment reduced HbA1c by ~5 mmol/L (~10%) across dose groups (p&lt;0.05). Insulin resistance (HOMA2-IR) decreased by 39% vs. placebo overall (p=0.017), with corresponding decreases in fasting insulin, while β-cell function (HOMA2-β) exhibited a marked dose-dependent increase (163% at the 80 mg dose, p&lt;0.05). Overall, ALP001E was safe and well-tolerated at all doses; all reported TEAEs were mild, with no dose discontinuation or dose-changes secondary to AEs.
Conclusion: ALP001E has robust therapeutic potential for improving insulin resistance and glycemic control in patients with T2D.

Disclosure
C. Chung: Board Member; Alphala Group Inc. Caymen. S. Tseng: None. P. Chan: Employee; CMC Magnetics Corporation. G. Castro: None. Y. Chen: Employee; CMC Magnetics Corporation. C. Hsu: None. M.B. Zemel: Consultant; Enterin, TIXiMed, Glyscend Inc. Board Member; NuSirt. Consultant; Levicure, Seraxis, Aerami, Zealand Pharma A/S, Adipopharm.
848-P: Comparing Generative AI to Human Responses for Personalized Diabetes Drug Selection
Authors: FLORY JAMES , ANCKER JESSICA , KUPERMAN GILAD , VICKERS ANDREW , KIM SCOTT Y. , PETROV ALEKSANDR 
Published: June 2024

Introduction and Objective: Generative artificial intelligence (AI) offers great promise for clinical decision support (CDS). When there is a single right answer to a clinical question, assessing whether a generative AI is appropriate for CDS may be simple: does it give the correct answer often enough? When there is not a clear best answer, assessing AI performance is more complex.
Methods: This study compares endocrinologist and AI (Chat GPT-4) responses to clinical vignettes in which the respondent was asked to choose an initial medication for a patient with type 2 diabetes. Each vignette included patient characteristics such as lab values, demographics, and comorbidities. Use versus non-use of metformin was the primary outcome. Univariable analysis was used to explore how other patient characteristics influenced willingness to use metformin.
Results: Both endocrinologists (n=30) and AI were unlikely to recommend metformin in severely impaired kidney function (Figure 1A). Patient characteristics affected human and AI responses in similar ways (Figure 1B). Human respondents were slightly less likely to use metformin in patients with history of gastrointestinal symptoms, while the AI never used metformin in those circumstances.
Conclusion: When multiple treatment options were reasonable, AI responses were similar to human responses in quality and in how treatment decisions were personalized.

Disclosure
J. Flory: None. J. Ancker: Other Relationship; Ambry Genetics. G. Kuperman: None. A. Vickers: None. S.Y. Kim: None. A. Petrov: None.

Funding
Patient Centered Outcomes Research Institute (ME-2022C1-26378)
853-P: Efficacy and Safety of HD-6277, a Novel GPR40 Agonist, in Patients with Type 2 Diabetes—A Double-Blind, Randomized, Placebo-Controlled, Parallel-Group, Multicenter Phase 2 Trial
Authors: LEE YONG-HO , MIN KYUNGWAN , HWA HONG JUN , LIM SOO , YU JAEMYUNG , CHUNG CHOON H. , SUNG MOON JUN , CHUL WON JONG , WOO AHN CHUL , LEE JIE-EUN , NYUN KIM TAE , LEE BYUNG-WAN 
Published: June 2024

Objective: To assess the efficacy and safety of HD-6277, the first candidate of GPR40 in a new oral antidiabetic agent, in Adult Patients With Inadequate Control of Type 2 Diabetes Mellitus (T2DM)
Research Design & Methods: A double-blind, randomized, placebo-controlled phase 2 trial recruited 112 participants aged ≥ 20 years with T2DM with HbA1c between 7.0% and 10.0% while on diet and exercise alone for at least 8 weeks prior to screening. Parallel-group, randomized trial of HD-6277 50mg and 100mg group versus placebo were assigned for 12 weeks. The primary outcome was change in HbA1c at week 12 from baseline. Secondary outcomes included proportion of patients achieving HbA1c less than 7.0%, change in fasting plasma glucose(FPG), Changes in blood levels of post-meal glucose, insulin, glycoalbumin(GA), and C-peptide at week 12. In addition, changes in fasting lipid parameters, weight, GA/HbA1c ratio, HOMA (Homeostasis Model Assessment) β, and CD 36 were evaluated as exploratory endpoints.
Results: At week 12, compared to the placebo group, HD-6277 50mg and 100mg resulted in a statistically significant reduction of HbA1c levels by -0.73(95% CI -1.11, -0.35), p=0.0002 and -0.85 (95% CI -1.21, -0.50), P&lt;0.0001, respectively. No significant increase in treatment-related adverse events was observed for HD-6277. Furthermore, significant improvements in FPG and GA levels were confirmed in the HD-6277 administration group compared to the placebo.
Conclusion: HD-6277 50mg and 100 mg improved glycaemic control in patients with T2DM inadequately controlled with diet and exercise, as shown by significant changes in HbA1c and FPG. The treatment with HD-6277 appeared to be safe and well tolerated. A GPR40 agonist represents a potential new treatment option for T2DM.

Disclosure
Y. Lee: None. K. Min: None. J. Hong: None. S. Lim: None. J. Yu: None. C.H. Chung: None. J. Moon: None. J. Won: None. C. Ahn: None. J. Lee: None. T. Kim: None. B. Lee: Research Support; Hyundai Pharm.

Funding
This study was sponsored by Hyundai Pharmaceutical Co., Ltd. (ClinicalTrials.gov registration number: NCT05666128).
855-P: GLY-200 (Oral Pharmacologic Duodenal Exclusion Drug) Reduces Glucose and Bodyweight in Patients with Type 2 Diabetes
Authors: FINEMAN MARK , COLBERT KEVIN , PETERSEN JOHN S. , JOZEFIAK THOMAS H. , NIMGAONKAR ASHISH , BRYANT CHRISTINE 
Published: June 2024

Background: GLY-200 is an investigational oral non-absorbed polymer drug designed to bind to and enhance the barrier function of gastrointestinal mucus as a non-invasive alternative to metabolic surgery and duodenal exclusion devices. In healthy volunteers, GLY-200 lowered glucose and increased GLP-1, PYY, and bile acids, indicating pharmacologic effects in the proximal small intestine. This study evaluated the safety, tolerability, and pharmacodynamic effects of GLY-200 in patients with type 2 diabetes (T2D).
Methods: In this randomized, double-blind, placebo (PBO)-controlled study, 51 patients with T2D [BMI 31.3 ± 4.2 kg/m2, baseline (BL) HbA1c 7.12 ± 0.57%] received 14 days of 0.5, 1.0, or 2.0 g GLY-200 or PBO, BID. Assessments included safety/tolerability, food intake, appetite, body weight (BW), glucose profiles after a standardized meal, and CGM.
Results: GLY-200 appeared safe and well-tolerated with most AEs being GI-related. Glucose was reduced on Day 1 in the 2.0 g GLY-200 group and reduced over time with lower doses. Day 14 iAUC was ↓27% (p=0.11), ↓29% (p=0.13), and ↓44% (p=0.01) in the 0.5, 1.0, and 2.0 g GLY-200 groups, respectively, vs PBO. At Day 14, the mean change from BL in fasting serum glucose was ‑16.1, -10.7, -16.1 mg/dL for the 0.5, 1.0, and 2.0 g GLY-200 groups, respectively, compared to an increase of 12.1 mg/dL in the PBO group. Decreases from BL in total and LDL cholesterol were also seen at Day 7 and 14 in 1.0 g and 2.0 g GLY-200 groups. Progressive reductions in BW were seen over the 14-day treatment period, with the largest reductions seen with 2.0 g GLY-200 (up to -1.8% change from BL). 2.0 g GLY-200 subjects also reported reduced appetite, increased satiation, and reduced food intake.
Conclusion: GLY-200 treatment resulted in positive effects on fasting and postprandial glucose, lipid profiles, food intake, appetite suppression, and BW consistent with the antidiabetic and anti-obesity effects of other more invasive approaches to duodenal exclusion.

Disclosure
M. Fineman: Employee; Glyscend Inc. K. Colbert: Employee; Glyscend Inc. Consultant; LifeSprout Inc. J.S. Petersen: None. T.H. Jozefiak: Employee; Glyscend Inc. A. Nimgaonkar: None. C. Bryant: Employee; Glyscend Inc.
856-P: Prevention of Type 1 Diabetes with MSC-EV
Authors: GU ANGEL S. , BAG ARUP , HO YINWEI , RAO ANITHA , RODRIGUEZ KEITH , MIAO LYNN N. , RAWSON JEFFREY , HUSSEINY MOHAMED I. , KANDEEL FOUAD R. 
Published: June 2024

Objective: Type 1 diabetes (T1D) is an autoimmune disease characterized by immune cell-mediated destruction of beta cells resulting in loss of insulin production and glucose homeostasis. Mesenchymal stem cells (MSCs) are a heterogeneous population of adult stem cells that can be isolated from many tissues including umbilical cords. Extracellular vehicles (EVs) derived from human MSCs have been proposed to have the potential for restoring immune tolerance and to block the immune/inflammatory attack on beta cells. We examined the ability of human MSC-EV to prevent transfer of T1D in mice.
Methods: Adoptive transfer of T1D was performed in 7-week-old female NOD/SCID mice received 10 x 106 splenocytes from 12-week-old female NOD mice, followed 24 hours later with either PBS, 1 x 106 MSCs or 5 x 109 MSC-EVs, two doses each, 7 days apart. Blood glucose was monitored daily, and IPGTT was performed before animal sacrifice. Blood, splenocytes and pancreas were then harvested.
Results: Mice treated with EVs or MSCs showed reduction in the development of diabetes. More germane, EV-treated animals fared best with 75% showing no diabetes at 9 weeks post treatment. IPGTT data showed that mice treated with EVs have less rise in blood glucose and faster restoration towards baseline compared to MSC- and PBS-treated animals. Further, these mice showed less overall glucose variability during the test. The splenocytes from EV-treated mice produced significantly less inflammatory cytokines MIP-2, IL-1α and IL-12 and more anti-inflammatory IL-10 compared to splenocytes from PBS-treated mice. FACS analysis found more regulatory CD4/Foxp3 and CD4/CD25/Foxp3 positive T cells in the circulation of EV-treated mice compared to controls. MSC and EV-treated mice displayed more insulin-positive beta cells compared to PBS-treated animals, but density of these cells were less in the MSC than the EV-treated group.
Conclusion: MSC-EV therapy can prevent development of T1D more effectively than MSCs, presenting a huge opportunity for patients at risk or having established T1D.

Disclosure
A.S. Gu: None. A. Bag: None. Y. Ho: None. A. Rao: None. K. Rodriguez: None. L.N. Miao: None. J. Rawson: None. M.I. Husseiny: None. F.R. Kandeel: Advisory Panel; Vertex Pharmaceuticals Incorporated.
864-P: GLY-200 (Oral Pharmacologic Duodenal Exclusion Drug) Decreases Appetite, Increases Satiation, and Reduces Food Intake in Patients with Type 2 Diabetes
Authors: BRYANT CHRISTINE , NIMGAONKAR ASHISH , FINEMAN MARK 
Published: June 2024

Background: GLY-200 is an investigational oral non-absorbed polymeric drug designed to bind to and enhance the barrier function of gastrointestinal mucus as a non-invasive alternative to metabolic surgery and duodenal exclusion devices. In healthy volunteers, GLY-200 lowered glucose and increased GLP-1, PYY, and bile acids, indicating pharmacologic effects of duodenal targeting. This 14-day Ph2 study in patients with type 2 diabetes (T2D) evaluated the safety, tolerability, and pharmacodynamic effects of GLY-200 and showed reduced glucose and progressive body weight loss at the 2.0 g GLY-200 dose.
Methods: Randomized, double-blind, placebo (PBO)-controlled inpatient study with 14 days BID dosing of 2.0 g GLY-200 [N=13, BMI 31.8 ± 4.1 kg/m2, baseline (BL) HbA1c 7.2 ± 0.7%] and PBO (N=12, BMI 31.7 ± 3.2 kg/m2, BL HbA1c 7.2 ± 0.7%). On Day -1, 1, and 13, food intake and appetite VAS were assessed at standardized breakfasts and ad libitum dinners. Categorical food intake (0-25%, 26-50%, 51-75%, 76-100% consumed) was assessed at all other inpatient meals.
Results: GLY-200 appeared safe and well-tolerated with most AEs being GI-related. With 2.0 g GLY-200, a greater overall appetite suppression (OAS) score was seen immediately post-meal (↑35.9%, p=0.004) and 60 min after the standardized breakfast (↑28.7, p=0.02) vs PBO. Before the ad libitum dinner, the OAS score was ↑28% (p=0.004) in 2.0 g GLY-200 subjects vs PBO. When allowed to eat as much as desired, 2.0 g GLY-200 subjects had significantly lower food intake (↓17.0%, p=0.026). During non-standardized inpatient meals, an average of 22.1%, 19.5%, and 28% of 2.0 g GLY-200 subjects consumed ≤75% of breakfast, lunch, and dinner, respectively, vs 0%, 4.8% and 6.8% of PBO subjects.
Conclusion: Increased satiation/satiety, decreased feeling of hunger, and reduced food intake, in part, explains the body weight loss observed with 2.0 g GLY-200 treatment, consistent with the intended mechanism of the drug.

Disclosure
C. Bryant: Employee; Glyscend Inc. A. Nimgaonkar: None. M. Fineman: Employee; Glyscend Inc.