bluuebunny/crossref_metadata_2025_split huggingface dataset:
842-P: Improvement in Time in Range after Smart Insulin Pen Initiation in Austria
Authors: MADER JULIA K. , HARTVIG NIELS V. , KAAS ANNE , KNUDSEN NIKOLINE N. , WINHOFER YVONNE 
Published: June 2024

Introduction & Objectives: A prior multinational study showed improved time in range (TIR; 70-180 mg/dL) in people living with type 1 or type 2 diabetes (PLWD) after smart pen initiation for their bolus insulin. To understand country-specific experiences with smart pen use, this study replicated the analysis, focusing on PLWD in Austria.
Methods: Real-world data (RWD) were collected from adults in Austria on a multiple daily insulin regimen who were already using a continuous glucose monitoring (CGM) device and initiating a smart pen. Days were included if an individual had ≥1 data upload (pen to app) within the last 14 days and ≥15% time covered by CGM sensor readings. Key glycemic outcomes were TIR and time below range (TBR; &lt;3.9 mmol/L).
Results: Data from 1336 adults (mean 49.1 years) were analyzed (101 394 days with CGM data and recorded bolus injections). Mean TIR increased by 4.0% at month 3 (95% CI 3.0, 5.1; p &lt; 0.001) and was sustained at month 6 (95% CI 2.7, 5.2; p &lt; 0.001) (Figure). TBR decreased significantly from baseline by month 3, but was not statistically significant at month 6. The percentage of participants with TIR &gt;70% increased from 35% at baseline to 42% at 6 months (p &lt; 0.001).
Conclusion: RWD from Austria shows a clear glycemic improvement after smart pen initiation. Analyzing country-specific experiences is important to understand the potential impact of smart pen use and how PLWD and physicians can most benefit from this technology.

Disclosure
J.K. Mader: Advisory Panel; Becton, Dickinson and Company. Speaker's Bureau; Becton, Dickinson and Company, A. Menarini Diagnostics, Boehringer-Ingelheim, diaTribe. Other Relationship; Diabetes UK. Stock/Shareholder; decide Clinical Software GmbH. Advisory Panel; embecta. Speaker's Bureau; embecta, Viatris Inc., Eli Lilly and Company. Advisory Panel; Eli Lilly and Company, Medtronic. Speaker's Bureau; Medtrust. Advisory Panel; Novo Nordisk A/S. Speaker's Bureau; Novo Nordisk A/S. Advisory Panel; PharmaSens, Roche Diabetes Care. Speaker's Bureau; Roche Diabetes Care. Board Member; Sanofi-Aventis Deutschland GmbH. Speaker's Bureau; Sanofi-Aventis Deutschland GmbH, Sanofi, Dexcom, Inc., Viatris Inc. Advisory Panel; Viatris Inc. Speaker's Bureau; Ypsomed AG. Research Support; European Union. Stock/Shareholder; elyte Diagnostics GmbH. Other Relationship; elyte Diagnostics GmbH. Board Member; European Association for the Study of Diabetes. Research Support; European Union Aviation Safety Agency. N.V. Hartvig: Stock/Shareholder; Novo Nordisk A/S. Employee; Novo Nordisk A/S. A. Kaas: Employee; Novo Nordisk A/S. Stock/Shareholder; Novo Nordisk A/S. N.N. Knudsen: Employee; Novo Nordisk. Stock/Shareholder; Novo Nordisk. Y. Winhofer: None.

Funding
Novo Nordisk A/S
849-P: Safety, Tolerability, Pharmacokinetics (PK), and Pharmacodynamics (PD) of an Optimized Dual GLP-1/GIP Receptor Agonist (BGM0504) in Healthy Subjects—A Phase Ia, Randomized, Double-Blind, Placebo-Controlled, Ascending Dose Study
Authors: YUAN JIANDONG , HUANG YANGQING , DING HAIFENG , JIANG XIAOHUI 
Published: June 2024

Background: BGM0504 is an optimized dual GIP and GLP-1 receptor agonist with greater in vitro potency, and similar GLP-1R/GIPR activity ratio as Tirzepatide. Here we report the results of a phase Ia study of BGM0504 in healthy subjects (CTR20230120).
Methods: In a clinical study of 40 healthy subjects, four initially received a single 2.5 mg subcutaneous injection of BGM0504. The remaining 36 were divided into three groups, each receiving two weekly injections at escalating doses: 2.5/5 mg, 5/10 mg, and 10/15 mg, respectively. In each group, 10 subjects were randomly assigned to BGM0504, and 2 received a placebo. The primary endpoints were safety and tolerability. The secondary endpoints included PK and PD.
Results: In the study with 40 healthy subjects, gastrointestinal adverse events like decreased appetite, nausea, abdominal distension, vomiting, and diarrhea were most common, all mild to moderate. The concentration of BGM0504 peaked between 24 to 72 hours post-dosing, with a mean half-life of approximately 4 days, supporting a weekly dosing schedule. BGM0504 showed dose-proportional PK within the tested range, with slightly higher exposures (Cmax and AUC) than Tirzepatide at equivalent doses. Subjects experienced a dose-dependent weight loss ranging from 3.24% to 8.30% by study end, with no significant changes in other PD markers like glycemia, C-peptide, and insulin.
Conclusions: BGM0504 was well tolerated with favorable PK profile and led to evident body weight loss. These data support further clinical developments of BGM0504 for T2DM and obesity. The phase II clinical trials for both T2DM and obesity are ongoing, and available results will be presented.

Disclosure
J. Yuan: Other Relationship; BrightGene Bio-Medical Technology Co., Ltd. Y. Huang: Employee; BrightGene Bio-Medical Technology Company Ltd. H. Ding: Employee; BrightGene Bio-Medical Technology Company Ltd. X. Jiang: Consultant; BrightGene Bio-Medical Technology Co Ltd.
850-P: Trends in GLP-1RA Use among Individuals with Type 2 Diabetes (T2D) and/or Obesity—Insights from a Nationwide Electronic Health Record System, 2010–2023
Authors: LI PIAOPIAO , SAM VARGHESE JITHIN , SHAH MEGHA K. , PASQUEL FRANCISCO J. , HARDING JESSICA L. , JIAO TIANZE , SHAO HUI , ALI MOHAMMED K. 
Published: June 2024

New evidence highlights GLP-1 RAs' significant benefits in blood glucose and weight control for those with T2D and/or obesity, yet their real-world use and related disparities are unexplored. We conducted a pooled cross-sectional study using electronic health records from the Epic Cosmos database (2010-2023), an integrated database covering 176 million patients across 50 US states. We examined trends in GLP1-RA use among three groups: T2D-only, obesity-only, and T2D with obesity. The trend was also examined by socio-demographic factors in each group. The study included a sample of 67.9 million individuals. A gradual increase in GLP-1RA use was observed across all groups from 2010 to 2016, followed by a pronounced and accelerated uptake since 2016 (Figure). In the obesity-only population, females exhibited a 1.47 times faster uptake rate than males, measured by the annual rate of increase. Similarly, those with education beyond college showed a 1.76 times faster uptake rate than their counterparts. The utilization rate for individuals under 19 years with T2D and obesity, which remained at 0% from 2010 to 2017, surged to 35.3% in 2023. We found an upward trend in GLP-1 RA utilization since 2016 when FDA approval occurred, though use was disproportionate among some groups, raising concerns about inequitable access.

Disclosure
P. Li: None. J. Varghese: None. M.K. Shah: None. F.J. Pasquel: Research Support; Tandem Diabetes Care, Inc., Insulet Corporation, Dexcom, Inc., Ideal Medical Technologies, Novo Nordisk. Consultant; Dexcom, Inc., Medscape. J.L. Harding: None. T. Jiao: None. H. Shao: Consultant; Eli Lilly and Company. M.K. Ali: Advisory Panel; Eli Lilly and Company.
852-P: Effect of Metformin on Intestinal Flora in Patients with Polycystic Ovary Syndrome
Authors: XU LAN , JIE JIANG CHEN 
Published: June 2024

Objective: To analyze the characteristics of the intestinal flora of patients with polycystic ovary syndrome (PCOS) in reproductive age, and to explore the effect of metformin on the intestinal flora of PCOS patients.
Methods: Thirty-six PCOS patients attending Wuxi People's Hospital affiliated to Nanjing Medical University from 2019 to 2021 were selected as the study group and 35 healthy women of childbearing age during the same period as the control group, and metformin treatment was given to the PCOS patients for 6 months, and blood and fecal specimens were collected before and after treatment. 16S rDNA was used to identify the intestinal flora of the fecal specimens.
Results: (1) The α and β diversity of the intestinal flora was lower in the study group, and the abundance of Bacteroidaceae, Oscillospiraceae, Rikenellaceae, and Clostridiaceae UCG-014 was lower than that of the control group, while Enterobacteriaceae was more abundant, and after correction for BMI, there was still a significant difference between Bacteroidaceae and Enterobacteriaceae. (2) After metformin treatment, and the abundance of Bacteroidaceae in the study group increased, while the abundance of Peptostreptococcaceae and Clostridiaceae decreased. (3) Correlation analyses showed that the abundance of Bacteroidaceae was negatively correlated with testosterone, antimüllerian hormone, and lipids; the abundance of Enterobacteriaceae was positively correlated with testosterone, antimüllerian hormone, blood glucose and insulin. (4) Changes in the abundance of Bacteroidaceae before and after treatment with metformin in the study group were negatively correlated with changes in total cholesterol; changes in the abundance of Peptostreptococcaceae were positively correlated with changes in total cholesterol and low-density lipoprotein cholesterol.
Conclusion: Intestinal flora disorders exist in PCOS patients, and metformin has an ameliorating effect on intestinal flora disorders in PCOS patients.

Disclosure
L. Xu: None. C. Jiang: None.
859-P: ALN-KHK, an Investigational RNA Interference Therapeutic, Successfully Targets Hepatic Ketohexokinase in a Single Ascending Dose Study of Overweight to Obese Adults
Authors: MARATOS-FLIER ELEFTHERIA , NANDI TIRTHA , BOYLE KATHERINE , LI XINGYU , WU YUANFENG , NOETZLI LEILA , KAJBAF FARSHAD , MORELLI GAETANO 
Published: June 2024

Introduction & Objective: Rising obesity rates are attributed in part to high dietary sugar consumption, including fructose, which is linked to development of hepatosteatosis and type 2 diabetes. ALN-KHK is an investigational RNA interference therapeutic designed to decrease hepatic ketohexokinase (KHK) expression, thus reducing fructose metabolism by targeting its initial step and potentially decreasing hepatic lipogenesis. The objectives of this Phase 1/2 Part A single ascending dose study (NCT05761301) were to evaluate safety, tolerability, and pharmacology of ALN-KHK in overweight to obese adults.
Methods: Healthy adults with a BMI of 27-34.9 kg/m2 were randomized 3:1 to receive a single subcutaneous dose of ALN-KHK or placebo. Five dose cohorts (25, 75, 150, 300, and 600 mg) were evaluated over a 3-month period with follow up for up to 9 months. The primary endpoint assessed safety and tolerability. Secondary endpoints characterized pharmacokinetics and pharmacodynamics of ALN-KHK after a fructose tolerance test (FTT) prior to dosing and on Days 29, 57, 85, and 169.
Results: Forty participants enrolled (N=30, ALN-KHK; N=10, placebo; mean (SD) age, 45.4 (11.5) years; mean (SD) BMI, 29.7 (1.7) kg/m2; 67.5% male). By data cutoff, all adverse events were mild, non-serious, and resolved. Increasing doses of ALN-KHK were generally associated with dose- and time-dependent increases in serum fructose area under the curve (AUC) and urinary fructose fraction excreted after FTT. Preliminary data showed a mean (SD) increase from baseline of 178.0% (84.4%) in serum fructose AUC with 300 mg at Day 85. Reduction of fibroblast growth factor 21 after FTT was also observed.
Conclusion: Interim results of this first clinical study of ALN-KHK demonstrate an encouraging safety and tolerability profile with target engagement in overweight to obese adults, supporting its further evaluation in patients with type 2 diabetes.

Disclosure
E. Maratos-Flier: Employee; Alnylam Pharmaceuticals. T. Nandi: None. K. Boyle: Employee; Alnylam Pharmaceuticals, Inc. X. Li: None. Y. Wu: Employee; Alnylam Pharmaceuticals, Inc. L. Noetzli: Employee; Alnylam Pharmaceuticals, Inc. Stock/Shareholder; Alnylam Pharmaceuticals, Inc. F. Kajbaf: Employee; Alnylam Pharmaceuticals, Inc. G. Morelli: None.

Funding
Alnylam Pharmaceuticals, Inc.
865-P: Metformin Reduces Insulin Dose and Visceral Fat Accumulation, and Increases GDF15 without Reducing Insulin Resistance in Adults with Type 1 Diabetes—A 26-Week, Randomized, Double-Blind Placebo-Controlled Trial (INTIMET)
Authors: SNAITH JENNIFER R. , OLSEN NICHOLAS D. , KOWALSKI GREG M. , BRUCE CLINTON , EVANS JENNIFER L. , JANUSZEWSKI ANDRZEJ S. , JENKINS ALICIA , BREIT SAMUEL N. , HOLMES-WALKER JANE , GREENFIELD JERRY 
Published: June 2024

Insulin resistance is a cardiovascular (CV) risk factor in type 1 diabetes (T1D). The effect of metformin on liver and muscle insulin resistance has not been studied in adults with T1D. We recruited 40 adults with T1D (HbA1c 7.5±0.9% [58±10mmol/mol], diabetes duration 22.9±8.9 years, age 37.4±8.8 years, 60% male, BMI 26.4±3.8 kg/m2). Twenty age, gender and BMI matched controls without diabetes were studied at baseline only. Subjects with T1D were randomized to metformin XR 1500mg daily or placebo for 26 weeks. At baseline and end of treatment, subjects completed two-step hyperinsulinemic-euglycemic clamps with 6,6-2H2 glucose to measure insulin sensitivity at liver (endogenous glucose production during low dose insulin infusion; EGP) and muscle (glucose infusion rate during high dose insulin infusion; GIR). Arterial stiffness (augmentation index; AIx), body composition (DXA, MRI), continuous glucose monitoring (CGM) and growth differentiation factor 15 (GDF15) were measured. Adults with T1D displayed insulin resistance in muscle (GIR 29% lower) and liver (EGP 64% higher). After 26 weeks, metformin reduced total daily insulin dose (estimated treatment difference [ETD] -6.5 units/day [95% CI -11.4 to -1.7]; p=0.009) and visceral fat (p=0.04), and increased serum GDF15 levels (ETD 382 pg/mL [59 to 704]; p&lt;0.001). Metformin did not improve EGP, GIR, AIx, body composition, HbA1c or CGM time in range vs placebo. Metformin reduced insulin dose and visceral fat, and increased GDF15, without improving insulin resistance. This insulin dose difference was previously associated with a 6% CV risk difference. This study: 1) Implicates insulin resistance-independent actions of metformin; 2) Highlights reducing insulin dose as a possible mediator of metformin’s cardioprotection; and 3) Postulates that metformin’s effects in adults with T1D may involve GDF15.

Disclosure
J.R. Snaith: None. N.D. Olsen: Stock/Shareholder; Pfizer Inc. G.M. Kowalski: None. C. Bruce: None. J.L. Evans: None. A.S. Januszewski: None. A. Jenkins: Research Support; Abbott, Viatris Inc. Advisory Panel; Abbott. Research Support; Medtronic. Board Member; Insulin for Life. Research Support; Leona M. and Harry B. Helmsley Charitable Trust, Juvenile Diabetes Research Foundation (JDRF), Jaeb Center for Health Research, National Institutes of Health, National Health and Medical Research Council Australia. S.N. Breit: Other Relationship; Novo Nordisk A/S, Aveo Pharmaceutical, Roche Diagnostics. J. Holmes-Walker: None. J. Greenfield: Other Relationship; Novo Nordisk.

Funding
Diabetes Australia; St Vincent's Clinic Foundation; UNSW Cardiac, Vascular and Metabolic Medicine Theme; National Health and Medical Research Council (NHMRC)
869-P: Gastrin Reduces Incidence of Type 1 Diabetes through Reducing Inflammation and Preserving ß-Cell Mass in Animal Model
Authors: MIAO LYNN N. , GU ANGEL S. , HUSSEINY MOHAMED I. , RAWSON JEFFREY , MARES JACOB , ORR CHRIS , DHAWAN SANGEETA , SHIH BEN , KU HSUN T. , KANDEEL FOUAD R. 
Published: June 2024

Introduction: Progressive destruction of insulin-producing β-cells by autoimmunity is a primary feature of type 1 diabetes (T1D). Therapies that block immune attacks on islet cells and preserve or restore the functional β-cell mass are needed to halt or reverse disease progression. Here, we tested the therapeutic effects of GAST-17, an analogue of the natural gastric hormone that is produced by intestinal G cells and fetal islets, on preservation and restoration of β-cell mass in the NOD mice.
Methods: Normoglycemic female NOD mice were injected intraperitoneal with GAST-17 (300 or 600ug/kg/day) or saline (control) for 14-weeks. At end of the experiment, an intraperitoneal glucose tolerance test (IPGTT) was performed. Pancreatic tissues were examined for islets number, endocrine cell mass and inflammatory cell infiltration.
Results: GAST-17 treated animals had lower rates of diabetes incidents in a dose-dependent manner. Animals treated with 600 ug/kg/day of GAST-17, prevented diabetes in 70-80% compared to 20-57% in control, and area under the curve in IPGTT test was also lower compared to control (p&lt;0.05). Islet morphology was not different among the diabetic mice, but GAST-17 treated nondiabetic mice had lower inflammatory cell infiltration (p&lt;0.004), higher number of islets (p&lt;0.01) and larger endocrine cell mass/islet than nondiabetic controls (p&lt;0.01).Smaller (&lt;10026uM2) but not larger islets showed higher ratios of insulin to glucagon and insulin per islet area when compared to controls(p&lt;0.005). All normoglycemic animals had larger numbers of small islets, compared to larger islets that were closer to the ducts.
Conclusion: GAST-17 treatment protected NOD mice from the development of diabetes by reducing islet inflammatory cell invasion, preserving beta cell mass and likely augmenting islet neogenesis from a ductal origin. Lineage tracing experiments are ongoing.

Disclosure
L.N. Miao: None. A.S. Gu: None. M.I. Husseiny: None. J. Rawson: None. J. Mares: None. C. Orr: None. S. Dhawan: None. B. Shih: None. H.T. Ku: None. F.R. Kandeel: Advisory Panel; Vertex Pharmaceuticals Incorporated.
883-P: Brain-Directed AAV-FGF21 Gene Therapy Reverses Type 2 Diabetes, Obesity, and Cognitive Decline
Authors: BOSCH FATIMA , SACRISTAN VICTOR , RIBERA ALBERT , MARCÓ COSTA SARA , JAMBRINA CLAUDIA , JIMENEZ VERONICA , CASANA ESTEFANIA , LEON XAVIER , ELIAS GEMMA , FERRE TURA , FRANCKHAUSER SYLVIE , ELIAS IVET 
Published: June 2024

Introduction: Type 2 Diabetes (TD2) and obesity are closely related metabolic diseases with an increasing worldwide prevalence. TD2 and obese patients have high risk of developing cognitive decline in the long-term. Fibroblast growth factor 21 (FGF21) has become a promising therapeutic agent for the treatment of obesity and T2D. It has been reported that FGF21 can act in different brain regions to regulate whole body metabolism.
Methods: Two-month-old C57Bl6 mice were fed either a chow or a HFD. Ten weeks later, mice were intra-cerebrospinal fluid (CSF) administered with adeno-associated viral (AAV) vectors encoding FGF21 (AAV-FGF21) and remained in HFD up to 14 months. Body weight, metabolic parameters and behavioral changes were determined at different time points after treatment.
&lt;u&gt;&lt;/u&gt; Results: Intra-CSF administration of AAV-FGF21 allowed specific overexpression of FGF21 in the CNS, without an increase in FGF21 circulating levels. Brain FGF21 expression resulted in normalization of body weight, adiposity, adipose tissue inflammation and hepatic steatosis and fibrosis. Moreover, AAV-FGF21 treatment counteracted HFD-induced insulin resistance, glucose intolerance and islet hyperplasia. This was parallel to enhanced energy expenditure resulting from FGF21 signaling in the CNS. Moreover, brain FGF21 expression also counteracted obesity-associated cognitive decline, prevented short-term and long-term memory loss, improved learning capacity and decreased anxiety-like behavior.
Conclusion: All these results underscore the potential of brain-directed AAV-FGF21 gene therapy to treat obesity, insulin resistance, T2D, and associated cognitive decline.

Disclosure
F. Bosch: None. V. Sacristan: None. A. Ribera: None. C. Jambrina: None. V. Jimenez: None. E. Casana: None. X. Leon: None. G. Elias: None. T. Ferre: None. S. Franckhauser: None. I. Elias: None.
916-P: SGLT2 Inhibitors and Parkinson’s Disease (PD) Risk in Older Populations with Type 2 Diabetes (T2D)
Authors: GUO JINGCHUAN , TANG HUILIN , SHAO HUI , LU YING , SHI LIZHENG , FONSECA VIVIAN , GUO YI , BIAN JIANG 
Published: June 2024

Background: Diabetes increases the risk of Parkinson’s disease (PD). SGLT2 inhibitors show neuroprotective effects in animal models. Yet evidence is limited regarding the effect of SGLT2 inhibitors on PD risk. We thus aimed to assess the association between SGLT2 inhibitors and PD risk in T2D patients.
Methods: In this retrospective cohort study, we used 2016-2020 national Medicare Claims data to identify beneficiaries with T2D and without preexisting PD. We compared the risk of PD between new users of SGLT2 inhibitors vs. DPP4 inhibitors. We employed 1:1 propensity score matching to balance the baseline confoundings between the treatment groups and applied Cox regression models to estimate the PD risk.
Results: After 1:1 propensity score matching, 26,619 individuals were included in each of the two treatment groups, the PD incidence was 2.48 and 3.54 per 1000 person-years in the SGLT2 inhibitor group and DPP4 inhibitor group, respectively. In the Cox model (Figure), the SGLT2 inhibitor group was associated with a significantly lower risk of incident PD (HR 0.70 [95% CI 0.55-0.89]) than the DPP4 inhibitor group. The risk reduction of PD was particularly profound in non-Hispanic Black individuals (HR 0.24 [95% CI 0.07-0.86]) and insulin users (HR 0.49 [95% CI 0.32-0.77]).
Conclusion: Compared to DPP4 inhibitors, SGLT2 inhibitors were associated with a significantly lower risk of indecent PD in people with T2D.

Disclosure
J. Guo: None. H. Tang: None. H. Shao: Consultant; Eli Lilly and Company. Y. Lu: None. L. Shi: None. V. Fonseca: Consultant; Abbott, Bayer Inc. Stock/Shareholder; BRAVO4HEALTH, LLC. Consultant; Corcept Therapeutics. Speaker's Bureau; Eli Lilly and Company. Research Support; Fractyl Health, Inc. Consultant; Sun Pharmaceutical Industries Ltd. Stock/Shareholder; Amgen Inc. Y. Guo: None. J. Bian: None.

Funding
National Institute of Diabetes and Digestive and Kidney Diseases (R01DK133465)
923-P: Effects of Ipragliflozin and Metformin on Hepatic Steatosis and Liver Fibrosis
Authors: KOSHIZAKA MASAYA , HIRAYAMA KIICHI , ISHIBASHI RYOICHI , SAKURAI KENICHI , YOKOTE KOUTARO 
Published: June 2024

Introduction & Objective: Diabetes and the liver are related. Obesity may affect the progression of metabolic dysfunction-associated steatotic liver disease (MASLD)/metabolic associated steatohepatitis (MASH). The effects of sodium-glucose transport protein 2 inhibitors (SGLT2is) on hepatic steatosis and liver fibrosis were examined in a subanalysis of a study that evaluated visceral fat area reduction related to ipragliflozin (SGLT2i) or metformin.
Methods: Overall, 103 Japanese patients with type 2 diabetes, a body mass index of &gt;22 kg/m2, and 7-10% glycated hemoglobin level were randomized to receive ipragliflozin 50 mg or metformin 1000 mg for 24 weeks. As hepatic steatosis indices, fatty liver index (FLI), hepatic steatosis index (HSI), and NAFLD-liver fat score (LFS) and as liver fibrosis indexes, AST to platelet ratio index (APRI) and fibrosis-4 (FIB-4) were compared between the groups.
Results: At baseline, intergroup differences in background characteristics or any index were insignificant. As the table shows, after 24 weeks, FLI, HSI, LFS, and APRI significantly improved in the ipragliflozin group.
Conclusion: Compared with metformin, ipragliflozin significantly improved multiple hepatic steatosis and liver fibrosis indexes, suggesting that ipragliflozin may alleviate hepatic steatosis, prevent liver fibrosis progression, and improve glycemic control. Therefore, it may prevent MASLD/MASH.

Disclosure
M. Koshizaka: None. K. Hirayama: None. R. Ishibashi: Research Support; Astellas Pharma Inc., Taiho Pharmaceutical Co. Ltd. K. Sakurai: None. K. Yokote: Research Support; Taisho Pharmaceutical Holdings Co., Ltd., Mitsubishi Tanabe Pharma Corporation, Boehringer-Ingelheim, Sumitomo Dainippon Pharma Co., Ltd., Kowa Company, Ltd. Speaker's Bureau; Kowa Company, Ltd., Sumitomo Dainippon Pharma Co., Ltd., Novo Nordisk, Novartis Pharmaceuticals Corporation, Daiichi Sankyo.