bluuebunny/crossref_metadata_2025_split huggingface dataset:
771-P: Efficacy of CT-996, an Oral Small Molecule GLP-1 Receptor Agonist, in Human GLP-1 Receptor Knockin Mice and Obese Cynomolgus Monkeys
Authors: LUO JIAN , RODRIGUEZ RUBEN , HERGARDEN ANNE , TRACY TED , LAM DAVINA , GARAI SUMANTA , MARSHALL DAN , HANSEN STIG K. , CHAKRAVARTHY MANU 
Published: June 2024

Since FDA approval of exenatide in 2005, injectable GLP-1 receptor agonists (RAs) have established their clinical utility in the management of type 2 diabetes and obesity. However, rising treatment utilization urgently necessitates cost-effective, simpler solutions. Here, we describe CT-996, a potent, oral small molecule GLP-1RA, and present preclinical efficacy studies to support its development for daily oral human use. In vitro, CT-996 was equally efficacious at stimulating cAMP accumulation in cells expressing human or cynomolgus monkey GLP-1R, and stimulated insulin secretion in a human β-cell line. In contrast to native GLP-1, CT-996 exhibited minimal β-arrestin recruitment and weaker GLP-1R internalization. In vivo, a single oral dose of CT-996 potently and effectively suppressed postprandial blood glucose following a mixed meal tolerance test (MMTT) in mice expressing the human GLP-1 receptor and, in obese monkeys, enhanced glucose stimulated insulin secretion (GSIS) during an intravenous glucose challenge. In a 4-week study in obese monkeys, daily CT-996 dosing markedly suppressed both plasma glucose and insulin excursion during MMTT. Compared to vehicle-treated animals, CT-996 significantly decreased food intake, body weight, and fat mass. All doses were well tolerated. In summary, CT-996 is a small molecule GLP-1RA that exhibits biased cAMP signaling and reduced receptor internalization. Oral dosing of CT-996 enhanced glucose homeostasis and reduced weight and fat mass after 4-week treatment in obese monkeys. These observations corroborate the continued development of CT-996 as a next-generation GLP-1RA. CT-996 is currently being evaluated in a Phase 1 clinical trial.

Disclosure
J. Luo: Employee; Carmot Therapeutics, Inc. R. Rodriguez: Employee; Carmot Therapeutics, Inc. A. Hergarden: Employee; Carmot Therapeutics, Inc. T. Tracy: Employee; Carmot Therapeutics, Inc. D. Lam: Employee; Carmot Therapeutics, Inc. S. Garai: None. D. Marshall: None. S.K. Hansen: Board Member; Carmot Therapeutics, Inc. M. Chakravarthy: Employee; Carmot Therapeutics, Inc.
787-P: Reducing Cardiometabolic Risk with Semaglutide in Type 1 Diabetes (RESET1)—A Double-Blinded Randomized Placebo-Controlled Trial (Study Protocol)
Authors: FRAMPTON RUTH , SNAITH JENNIFER R. , HOCKING SAMANTHA L. , GREENFIELD JERRY 
Published: June 2024

Background: Therapies are needed to address excess cardiovascular risk in type 1 diabetes. Once-weekly semaglutide, a long-acting glucagon-like peptide-1 receptor agonist, has been shown to improve weight, glycemia and reduce cardiovascular events in type 2 diabetes and obesity. Semaglutide may offer cardiometabolic protective benefits in type 1 diabetes. The REducing cardiometabolic risk with SEmaglutide in Type 1 diabetes (RESET1) study is a double-blind randomized, placebo-controlled trial of semaglutide in T1D.
Methods: We will study 60 adults aged 25-70 years with type 1 diabetes (duration &gt;2 years), body mass index ≥25 kg/m2, HbA1c ≥ 7% and at least 1 cardiovascular risk factor (microalbuminuria, hypertension or anti-hypertensive treatment, hyperlipidemia or lipid-lowering therapy, current smoking). Subjects will be randomized to semaglutide, titrated to 1.0mg weekly or volume-matched placebo for 26 weeks (supplied by Novo Nordisk A/S). The primary endpoint is carotid femoral pulse wave velocity, a measure of arterial stiffness and surrogate measure of cardiovascular risk. We will measure change in insulin sensitivity determined by hyperinsulinemic-euglycemic clamp; and incretin and pancreatic hormone action measured during mixed meal tolerance test to explore predictors and mechanisms for metabolic improvements. The trial is registered (Australian New Zealand Clinical Trial Registry, ACTRN12623001277639) and will be conducted in Sydney, Australia.
Conclusion: The RESET1 study will establish the effect of semaglutide on cardiometabolic health in adults with type 1 diabetes.

Disclosure
R. Frampton: None. J.R. Snaith: None. S.L. Hocking: Advisory Panel; Novo Nordisk. Other Relationship; Novo Nordisk. Advisory Panel; Eli Lilly and Company. Other Relationship; Eli Lilly and Company, iNova Pharmaceuticals Australia, Nestlé Health Science. Advisory Panel; Seqirus. Speaker's Bureau; AstraZeneca. Other Relationship; Amgen Inc., Sanofi. J. Greenfield: Other Relationship; Novo Nordisk.

Funding
Diabetes Australia Research Program (Charles Campbell Coghlan OAM Emerging Researcher Award), R.A.F. is supported by the University Postgraduate Award (University of New South Wales). J.R.S is supported by JDRF Australia (Grant# 3-SRA-2023-1296-M-N), the recipient of the Commonwealth of Australia grant for Accelerated Research under the Medical Research Future Fund
789-P: Discovery of a Novel, Long-Acting Amylin Receptor Agonist for Body Weight Control
Authors: LI YAN , ZOU HAIXIA , WU XINLE , ZHU RUI , WANG RUIPENG , HAO SUJUAN , LI ZHAOYING , WANG YAXU , DENG JIANHUI , WANG HONGYANG , PENG FEI , JONES CATHERINE L. , FENAUX MARTIJN 
Published: June 2024

Introduction & Objective: Amylin, a hormone co-secreted with insulin from pancreatic beta-cells, reduces food intake and glucagon levels. Combination of GLP-1 and amylin analogs promotes weight loss and glucose control. However, treatment is complicated by the need to formulate the peptides in different buffers. The objective of this study was to discover a novel amylin analog that could be co-formulated with GLP-1 peptides at neutral pH.
Methods: Peptides were designed and assessed for thermal-stressed stability (pH 7.4 at 40 oC for 20 days), as well as tested in CHO-K1 CRE reporter cells overexpressing the amylin receptor complex (calcitonin receptor and Ramp3) (AMY3) or calcitonin receptor alone (CTR), and evaluated for body weight reduction by single subcutaneous injection in SD rats. Cmpd C was selected and further characterized by once daily injection for 10 days in diet-induced obese (DIO) rat and pharmacokinetic (PK) study in cynomolgus monkey. Cagrilintide (Novo Nordisk), an amylin analog in Phase 3 studies, was used as a comparator.
Results: Among the peptides tested, Cmpd C activated AMY3 and CTR with similar potencies to cagrilintide (EC50 for Cmpd C and cagrilintide, respectively, AMY3: 0.038 nM vs 0.045 nM; CTR: 0.41 nM vs 0.45 nM). In SD rats, Cmpd C decreased body weight by 7.36% compared to 6.28% for cagrilintide over 48 hours. In DIO rats, body weight loss after end of dosing (Day 11) was 8.19% for Cmpd C and 7.55% for cagrilintide. In cynomolgus monkeys, Cmpd C showed comparable PK to cagrilintide. Importantly, Cmpd C showed superior thermal stability to cagrilintide at pH 7.4. While 44.83% of cagrilintide was degraded after 10 days, Cmpd C was reduced by 4.26% after 20 day incubation.
Conclusion: Overall, Cmpd C demonstrated potency and PK comparable to cagrilintide. Moreover, Cmpd C exhibited greater stability at pH 7.4 than cagrilintide, providing the opportunity to co-formulate with GLP-1 analogs. Formulation of GLP-1 and amylin in a single vial will improve ease of use and reduce cost.

Disclosure
Y. Li: Employee; Sciwind Biosciences. H. Zou: Employee; Sciwind Biosciences. X. Wu: Employee; Sciwind Biosciences. R. Zhu: Employee; Sciwind Biosciences. R. Wang: Employee; Sciwind Biosciences. S. Hao: Employee; Sciwind Biosciences. Z. Li: Employee; Sciwind Biosciences. Y. Wang: Employee; Sciwind Biosciences. J. Deng: Employee; Sciwind Biosciences. H. Wang: Employee; Sciwind Biosciences. F. Peng: Employee; Sciwind Biosciences. C.L. Jones: Employee; Sciwind Biosciences. M. Fenaux: None.

Funding
Sciwind Biosciences
8-PUB: Peer Support Defined by Key Functions—Implementation, Predicting Outcomes, and Mediation of Intervention Effects in Peer Support for Diabetes Management in Shanghai, China
Authors: LIU YUEXING , CAI CHUN , WU XIAOYU , TANG PATRICK Y. , COUFAL MUCHIEH M. , SHEN LI , FISHER EDWIN B. , JIA WEIPING 
Published: June 2024

What is peer support? Amidst great variation worldwide, Peers for Progress has promoted defining peer support (PS) by the “key functions” it provides. In a community PS program under the Shanghai Integration Model, key functions were measured by 15 items capturing participants’ reports of 1) Availability and Ongoing Support, 2) Assistance in Daily Management, 3) Social and Emotional Support, 4) Linkage to Clinical/Community Resources, 5) “Being There,” e.g., “people in the community diabetes program are there for you.”
The key functions documented implementation in 12 Intervention Communities (ICs) relative to 4 Comparison Communities (CCs) as well as relationships with outcomes and mediation of intervention effects.
At follow up, ICs scored higher than CCs on each of the 5 individual functions and their total, all, ps &lt; 0.001. On 5-point scales, mean differences between ICs and CCs ranged from 0.74 to 0.81.
Individual functions and total scores across the key functions were correlated with improvements in HbA1c, all p-levels &lt; 0.001. Similarly, each of the 5 and their total were also correlated with improvements in a 4-item measure of diabetes distress (ps ≤ 0.023) and the PHQ8 measure of depressed mood (ps &lt; 0.001). These controlled for gender, age, duration, and education level, as well as corresponding baseline measures.
Regression analysis indicated the total score for the 5 key functions mediated the relationship between the intervention, IC vs CC, and improvements in HbA1c, diabetes distress, and PHQ8.
The key functions identify features of PS that are recognized by program participants and help define PS as they distinguish PS from control conditions. The key functions are correlated with program benefits, and the total of reported key functions mediates the relationship between intervention and clinical/quality-of-life benefits.

Disclosure
Y. Liu: None. C. Cai: None. X. Wu: None. P.Y. Tang: None. M.M. Coufal: None. L. Shen: None. E.B. Fisher: None. W. Jia: None.

Funding
Shanghai Key Discipline of Public Health Grants Award No. GWVI-11.1-20, and Shanghai Municipal Grants Award No. GWIV-3.1 to Professor Weiping Jia as principal investigator, Shanghai Municipal Health Commission ôHealth Promotion Talentö grant No.JKKPYC-2022-12 to Dr. Yuexing Liu as principal investigator, and by grants from The Merck Foundation and from Sanofi China, both to Professor Edwin Fisher as principal investigator, and by the UNC-Michigan Communnity, Family, and Peer Support Core of the Michigan Center for Diabetes Translational Research, P30 DK092926.
80-OR: Association of Nonalcoholic Fatty Liver Disease and Liver Fibrosis with Cardiovascular Disease, All-Cause, and Cause-Specific Mortality in Individuals with Type 2 Diabetes
Authors: XU SHAOYONG , YOU QIQI , LIU LONGFU 
Published: June 2024

Introduction & Objective: The presence of NAFLD has been shown to significantly increase the risk of CVD and mortality, but their clarity in individuals with T2DM remains unclear. We aim to explore whether NAFLD and liver fibrosis affect CVD risk, all-cause and cause-specific mortality in individuals with T2DM.
Methods: This population-based cohort analyzed data of 14,990 individuals with T2DM from the UK biobank. NAFLD was identified by fatty liver index (FLI), and liver fibrosis was identified by BARD, Fibrosis-4 index (FIB-4) and NAFLD fibrosis score (NFS). Cox models were used to estimate the associations of NAFLD and liver fibrosis with CVD, all-cause and cause-specific mortality.
Results: Among 14,990 participants with T2DM (mean [SD] age, 58.7 [7.4] years; 8 237 [54.9%] men), there were 1,429 coronary heart disease, 985 heart failure, 595 stroke and 1,904 deaths. NAFLD was associated with an increased risk of coronary heart disease (HR: 1.65, 95% CI: 1.22-2.23), and a high FLI (quartile 4) was linked to a 110% higher risk of heart failure (95% CI: 1.52-2.90), a 91% higher risk of all-cause mortality (95% CI: 1.54-2.39), and an 83% higher risk of cancer mortality (95% CI: 1.30-2.59). Participants at high risk for fibrosis had a significantly higher risk of all-cause mortality than those at low risk for fibrosis (BARD, HR: 1.65, 95% CI: 1.14-2.38; FIB-4, HR: 1.68, 95% CI: 1.37-2.06; NFS, HR: 1.49, 95% CI: 1.29-1.73). A high risk for fibrosis determined by the NFS and FIB-4 was also linked with higher risks of mortality from CVD (HR: 1.59, 95% CI: 1.17-2.15) and cancer (HR: 1.53, 95% CI: 1.09-2.16), respectively.
Conclusion: These findings suggest that NAFLD and liver fibrosis are associated with elevated risks of major CVD, all-cause and cause-specific mortality in individuals with T2DM. Assessing individuals with T2DM for the presence and progression of NAFLD during clinical consultations is recommended.

Disclosure
S. Xu: None. Q. You: None. L. Liu: None.

Funding
This work was supported by the Key project of Hubei Natural Science Foundation Innovation and Development Joint Fund (Grant number 2023AFD031), and the Science and Technology Research Key Project of Education Department of Hubei Province China (Grant number D20212602).
806-P: Effectiveness of a Hybrid Weight Loss Program for Obesity and Prediabetes Using GLP-1 Medications
Authors: ZAKARIA HALA , CACCELLI MILENA , OZKAN CIGDEM , JAAFAR ZEINAB , SAID YOUSEF , ALEABOVA SOFIA , LABORTE REMIE IRENE A. , HASHEMI ALI , ALMARZOOQI IHSAN 
Published: June 2024

Anti-obesity GLP-1 agonists have widely been used by providers without emphasis on behavioral modification due to the short term effectiveness of these medications. The misuse of these medications without any monitored guidance on lifestyle changes can lead to significant weight regain. In this study, we will evaluate newer hybrid care models involving continuous engagement by multidisciplinary care teams on weight loss among those with pre-diabetes.This is a retrospective observational study of medical records for Zone.Health, a 6 months hybrid medicated obesity program, prescribed with both GLP-1 medications and multidimensional lifestyle modification (n=112). Behavioral change aspects of the program, delivered digitally via an app, included an accountability coach, use of food logging, CGM, and involvement of a personal trainer. Anthropometric data were recorded at the beginning and at 3 months. Majority received tirzepatide (51.8%), followed by semaglutide (46.4%), and a 1.8% received liraglutide. 3 months through the program, a significant -7.89 kg (-8.24%) weight loss (p &lt; 0.001) led to a 2.79-unit BMI decrease, including reduced fat mass (5.46 kg, p &lt; 0.001), improved cholesterol, LDL cholesterol, and triglycerides. In pre-diabetic patients (n=33) significant improvements in HbA1c of 0.46% (p &lt; 0.001) were observed leading to remission of all pre-diabetic patients. Weight loss was substantial at -6.85 kg (-6.8%) (p &lt; 0.001), with reductions in fat mass (-5.26 kg, -12.5% p &lt; 0.001). Total cholesterol levels decreased by -16.08 mg/dL (-8.3%) (p = 0.005). The hybrid program resulted in a 16.2% more reduction in weight compared to STEP-2 trial results which involved in-clinic only behavioral change advice.The use of GLP-1 medications delivered in a hybrid mode, demonstrated significant positive changes across all parameters, suggesting the potential of this approach for managing obesity and pre-diabetes using GLPs for more effective changes.

Disclosure
H. Zakaria: None. M. Caccelli: None. C. Ozkan: None. Z. Jaafar: None. Y. Said: None. S. Aleabova: None. R.A. Laborte: None. A. Hashemi: None. I. Almarzooqi: None.
807-P: GLP-1 Agonists and the Risk of Delayed Gastric Emptying in Elective Ophthalmic Procedures
Authors: COOPER AMELIA , LOPEZ ASHLEY , PACAS MIRANDA K. , STEVENS HENRY , MCKAY LISA A. , COOPER BLAKE 
Published: June 2024

Introduction & Objective: Concerns arise over delayed gastric emptying with Glucagon-like peptide-1 (GLP-1) receptor agonists in elective procedures. This study, in line with American Society of Anesthesiologists (ASA) guidelines, assesses perioperative effects, including evaluations of ASA scores and surgical outcomes, to address limited evidence highlighted by the ASA Task Force on Preoperative Fasting.
Methods: A three-month prospective chart review of patients undergoing ocular surgery with conscious sedation and a retrobulbar block with specific ASA preoperative instructions. When possible, patients on oral doses were instructed to hold the medication for 24 hours before surgery, while those receiving subcutaneous weekly doses were required to hold medication for one week and adhere to a clear liquid diet for 24 hours before surgery and maintain NPO status after midnight. Independent variables, including preoperative instructions and patient compliance, along with dependent variables such as preoperative blood sugar levels and complications, were analyzed.
Results: The prospective research study involved 20 participants, 6 males (30%) and 14 females (70%), with an average age of 68 years (SD: 9, range 54 to 88). Preoperative instructions were provided to 14 participants (70%), and there was complete compliance among the patients. The mean ASA score was 2.7 (SD: 0.57, range 2 to 4), and average preoperative glucose levels were 122 (SD: 29.4, range 95 to 210). There were no documented cases of aspiration and no difference between individuals who received preoperative instructions and those who did not, concerning glucose levels, coughing, desaturations, and the need for a jaw thrust in both scheduled and emergent surgeries.
Conclusion: Adhering to preoperative ASA guidelines, our results reveal no instances of aspiration despite concerns about delayed gastric emptying, offering insights into the safety and compliance implications of GLP-1 use in this patient group.

Disclosure
A. Cooper: None. A. Lopez: None. M.K. Pacas: None. H. Stevens: None. L.A. McKay: None. B. Cooper: None.
811-P: Safety and Effectiveness of iGlarLixi in People with Type 2 Diabetes Mellitus (T2DM) in South Korea
Authors: KIM HUN-SUNG , MIN KYUNGWAN , SOO KIM SANG , SOOK KIM EUN , CHUNG YOON-SOK , CHUNG CHOON H. , YUN JAE-SEUNG , KIM WON , HAN KIM DONG , JIB YOO SOON 
Published: June 2024

Introduction & Objective: The fixed ratio combination of insulin glargine and lixisenatide, iGlarLixi, was indicated as antihyperglycemic for people with T2DM and approved in November 2017 in South Korea. This post marketing surveillance (PMS) study aimed to evaluate the safety and effectiveness of iGlarLixi in clinical practice setting.
Methods: This study was a multicenter, prospective, single-arm, observational study conducted in Korean people with T2DM from August 2018 to August 2023. Primary endpoint was to investigate safety profile. Secondary endpoints included changes in HbA1c, FPG and 2-hour PPG from baseline to Week 12 and 24.
Results: Out of 743 people enrolled, 625 were included in safety evaluation and 519 in effectiveness evaluation. The mean age was 60.9 years and duration of T2DM was 13.6 years with equal proportions of male and female participants. Adverse events (AEs) and adverse drug reactions (ADRs) were reported in 120 (19.2%, 163 events) and 51 (8.2%, 63 events) participants, respectively. Most common AEs were gastrointestinal disorders (6.7%) such as nausea, decreased appetite, and vomiting. Significant reductions in HbA1c, FPG, 2-hour PPG were observed from baseline to Weeks 12 and 24 (Table).
Conclusion: In clinical practice, iGlarLixi has shown to be safe and well tolerated without new safety concerns improving clinical outcomes in people with T2DM in South Korea.

Disclosure
H. Kim: None. K. Min: None. S. Kim: None. E. Kim: None. Y. Chung: None. C.H. Chung: None. J. Yun: None. W. Kim: None. D. Kim: Employee; Sanofi, GlaxoSmithKline plc. S. Yoo: None.

Funding
Sanofi
813-P: Successful Use of Hybrid Closed Loop Insulin Pumps with GLP1 Agonists in Diabulimia and Disordered Eating in Type 1 Diabetes
Authors: BASAVARAJU NAVYA , JONES ANNAMARIE , MOULIK PROBAL 
Published: June 2024

Introduction:We present two cases of T1D with binge eating disorder(BED) benefitted by GLP-1 agonists with Hybrid closed loop(HCL) insulin pump(CSII).
Case 1:35-year-old female with T1D, obesity had high diabetes distress score(DDS), fear of hypoglycaemia, and emotional eating. She was on non-HCL CSII (Tandem Diabetes Care t:slim X2™ Insulin Pump), later Dexcom G6® Continuous Glucose Monitoring(CGM) with Control-IQ™ Technology and insulin Lispro for binge eating hyperglycaemia. She was supported by motivational interviewing, commenced Dulaglutide injections. Her food cravings reduced, felt positive about diabetes self-management and insulin requirement reduced by 25%.
Case 2:42-year-old female with T1DM, obesity, poor compliance, multiple diabetic ketoacidosis (DKA), nephropathy, retinopathy, diabulimia, high DDS; was commenced on Dulaglutide injections with HCL CSII (MiniMed™ 780G system with SmartGuard™ technology and Guardian™ 4 CGM). Renal function, quality of life score improved; insulin requirement reduced by 32%
Discussion:GLP-1 agonists with HCL CSII improved patient satisfaction scores, metabolic profile, weight, HbA1c, insulin requirement, blood pressure with no increase in DKA or hypoglycaemia. GLP-1 agonists are beneficial in binge eating without diabetes. Larger studies for complex T1D, diabetes distress, diabulimia may be warranted.

Disclosure
N. Basavaraju: None. A. Jones: None. P. Moulik: None.