bluuebunny/crossref_metadata_2025_split huggingface dataset:
750-P: Association of Glucagon-Like Peptide 1 Receptor Agonists with Incident Parkinson’s Disease in U.S. Older Adults with Type 2 Diabetes
Authors: TANG HUILIN , LU YING , OKUN MICHAEL S. , DONAHOO WILLIAM T. , RAMIREZ-ZAMORA ADOLFO , HUANG YU , ARMSTRONG MELISSA J. , SVENSSON MIKAEL , VIRNIG BETH , BIAN JIANG , GUO JINGCHUAN 
Published: June 2024

Background: Previous studies suggested the possibility of disease-modifying effects for glucagon-like peptide-1 receptor agonists (GLP-1RAs), but the evidence on the association between GLP-1RAs and risk of Parkinson’s disease(PD) remains to be clarified.
Methods: This population-based new-user cohort study included individuals with T2D who were newly prescribed a GLP-1RA or a dipeptidyl peptidase 4 inhibitor (DPP4i) using Medicare administrative data from Jan 2016 to Dec 2020. The primary endpoint was a new diagnosis of PD. A stabilized inverse probability of treatment weighting (sIPTW) - adjusted Cox proportional hazards regression was employed to estimate the hazard ratio (HR) of PD and 95% confidence intervals (CI) between GLP-1RA users and DPP4i users. Stratified analyses were performed, such as by age, sex, race/ethnicity, glucose-lowering drug (GLD) use at baseline, obesity at baseline, and molecule of GLP-1RA.
Results: A total of 89,074 Medicare beneficiaries who initiated either GLP-1RA inhibitor (n=30,091) or DPP4i (n=58,983) were included in the analysis. The crude incidence rate of PD was lower among GLP-1RA users (2.85 cases per 1000 person-years) when compared to DPP4i users (3.92 cases per 1000 person-years). An sIPTW-adjusted Cox model showed that GLP-1RA users were associated with a 23% lower risk of PD than DPP4i users (HR, 0.77; 95%CI, 0.63-0.95). Our findings were largely consistent across different subgroup analyses except for GLD use at baseline. A significantly lower risk of PD was observed among those using insulin at baseline and those with no GLD use at baseline, while no significant difference was detected among the groups using 1 GLD at baseline and ≥ 2 GLDs at baseline.
Conclusion: New use of GLP-1RAs was significantly associated with a lower risk of PD compared to new use of DPP4i in a large cohort of older adults with T2D.

Disclosure
H. Tang: None. Y. Lu: None. M.S. Okun: None. W.T. Donahoo: None. A. Ramirez-Zamora: None. Y. Huang: None. M.J. Armstrong: None. M. Svensson: None. B. Virnig: None. J. Bian: None. J. Guo: None.

Funding
American Foundation for Pharmaceutical Education Predoctoral Fellowship, PhRMA Foundation Predoctoral Fellowship, National Institutes of Health (NIH)/National Institute on Aging (NIA) (R01AG076234), and NIH/National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (R01DK133465).
752-P: Evaluating the Efficacy of Oral Semaglutide in Chinese Patients with Type 2 Diabetes by Baseline Characteristics—Post Hoc Analysis of PIONEER 11 and 12
Authors: JI LINONG , YUAN GUOYUE , LIU JUN , ZHANG BINGJIE , LIU WENYAN , SHEN ZEWEI 
Published: June 2024

Introduction & Objectives: Oral semaglutide, the only oral glucagon-like peptide-1 receptor agonist (GLP‑1RA) available for the treatment of T2D, is efficacious and has a safety profile consistent with the GLP-1RA class. This post hoc analysis of Chinese patients with T2D included in the PIONEER 11 and 12 trials investigates the efficacy of oral semaglutide vs comparators by different baseline (BL) characteristics.
Methods: Chinese patients with T2D (HbA1c 7.0-10.0% in PIONEER 11; 7.0-10.5% in PIONEER 12), aged ≥18 years, were randomized to once-daily oral semaglutide 3, 7 or 14 mg or comparator (placebo [PIONEER 11] or sitagliptin 100 mg [PIONEER 12]). Estimated change from BL in HbA1c and body weight were analyzed at week 26 by subgroups of BL characteristics, including age, GI disease and HbA1c.
Results: In total, 390 (PIONEER 11) and 1,084 (PIONEER 12) Chinese patients were evaluated. At baseline, mean HbA1c and body weight values were similar across most BL subgroups (data not shown). Overall, greater reductions in HbA1c and body weight were seen with oral semaglutide vs placebo or sitagliptin across the BL subgroups (Table 1).
Conclusion: Significant reductions in HbA1c and body weight were observed with oral semaglutide across BL subgroups, including age, GI disease and HbA1c,vs comparator.

Disclosure
L. Ji: None. G. Yuan: None. J. Liu: None. B. Zhang: None. W. Liu: Employee; Novo Nordisk A/S. Z. Shen: Employee; Novo Nordisk A/S. Stock/Shareholder; Novo Nordisk A/S.
757-P: Near-Normoglycemia and Insulin Regression Induced by Tirzepatide in Basal Insulin–Treated Type 2 Diabetes
Authors: ROSENSTOCK JULIO , TOFE SANTIAGO , WYSHAM CAROL H. , THIEU VIVIAN , KILJANSKI JACEK I. , LEE CLARE , WANG HUI , PATEL HIREN 
Published: June 2024

Introduction & Objective: In the SURPASS-6 trial, addition of tirzepatide (TZP) to basal insulin glargine U100 in participants with inadequately controlled long-standing type 2 diabetes (T2D), substantially improved HbA1c and body weight. We evaluated degrees of insulin dose reductions and the efficacy and safety of TZP based on residual insulin use at Week 52.
Methods: “Insulin regressor” was defined as basal insulin discontinuation or &lt;10 IU/day, and “insulin non-regressor” as ≥10 IU/day, at 52 weeks. Included only participants receiving TZP at Week 52 (≥75% compliance) without rescue medication. Efficacy analyses used a mixed model for repeated measures.
Results: Overall, 145 and 496 TZP-treated participants were included in the insulin regressor vs. insulin non-regressor groups, respectively. At baseline, mean age was 58.4 vs. 58.2 years, and median basal insulin dose was 40.0 vs. 48.0 IU/day. From baseline to Week 52 in the insulin regressor and insulin non-regressor groups, respectively, mean HbA1c of 8.5% and 8.9% was reduced to 5.9% and 6.7%, while weight was substantially reduced by 16 kg and 8 kg. Clinically significant hypoglycemia was also less frequent in the insulin regressor group (Table).
Conclusion: In basal insulin-treated T2D, participants who regressed on insulin use also achieved near-normoglycemia and substantial weight loss.

Disclosure
J. Rosenstock: Research Support; Biomea Fusion, Inc. Other Relationship; Lilly Diabetes. Research Support; Merck & Co., Inc., Novartis Pharmaceuticals Corporation, Corcept Therapeutics. Other Relationship; Novo Nordisk. Research Support; Pfizer Inc. Other Relationship; Sanofi, Boehringer-Ingelheim. Research Support; Shionogi & Co., Ltd. Other Relationship; Structure Therapeutics, Inc. Advisory Panel; Terns Pharmaceuticals, Zealand Pharma A/S. Other Relationship; Applied Therapeutics, Hanmi Pharm. Co., Ltd., Oramed Pharmaceuticals. Advisory Panel; Scholar Rock. S. Tofe: None. C.H. Wysham: Research Support; Eli Lilly and Company. Speaker's Bureau; Eli Lilly and Company. Research Support; Novo Nordisk. Consultant; Novo Nordisk. Speaker's Bureau; Novo Nordisk. Advisory Panel; Abbott. Research Support; Bayer Inc. Advisory Panel; Biomea Fusion, Inc. Research Support; Corcept Therapeutics, AbbVie Inc. V. Thieu: Employee; Eli Lilly and Company. J.I. Kiljanski: Employee; Eli Lilly and Company. Stock/Shareholder; Eli Lilly and Company. C. Lee: Employee; Eli Lilly and Company. Stock/Shareholder; Eli Lilly and Company. H. Wang: None. H. Patel: None.
760-P: TERN-501 Enhances Weight Loss Efficacy of a GLP-1R Agonist in Obese Mice via Increased Fat Mass Loss without Additional Loss of Lean Mass
Authors: JONES CHRISTOPHER , OSBORN OLIVIA , QUINN KEVIN P. , FEIGH MICHAEL , NYGAARD MADSEN ANDREAS , JASPER JEFFREY R. 
Published: June 2024

Introduction & Objective: GLP-1R agonists suppress food intake resulting in weight loss but efficacy is limited by metabolic adaptation, a compensatory process that lowers energy expenditure (EE). Thyroid hormone receptor beta (THRβ) regulates EE providing a potential mechanism to mitigate metabolic adaptation. TERN-501, a highly selective THRβ agonist, has shown excellent safety and significant liver fat reduction in a Ph2a study in patients with metabolic dysfunction-associated steatohepatitis. The combined effects of TERN-501 and GLP-1R agonism may offer benefits over either agent alone in reducing body weight.
Methods: Male C57BL/6JRj mice were fed high fat diet (60% HFD) for 24 weeks prior to study start. Mice (~55 g BW) were treated once daily with vehicle, TERN-501 (6 mg/kg PO), semaglutide (sema, 30 nmol/kg SQ), or 501+sema for up to 6-weeks at thermal neutrality. Body weight and food intake were measured daily. Body composition was assessed by EchoMRI and EE was measured in metabolic chambers.
Results: TERN-501 significantly enhanced the weight loss efficacy of sema (-26% vs -33%, p &lt;0.05) with increased fat mass loss (-11.8 g vs -15.2 g, p &lt;0.05) without additional loss of lean mass. In contrast, the effect of TERN-501 alone on body weight was similar to vehicle (-1.6% vs 1.5%, p &gt;0.05). In mice with higher initial body weight, 501+sema resulted in an additional 17% body weight loss vs sema alone. In combination with sema, TERN-501 prevented lowering of EE typically induced by weight loss and was associated with increased levels of UCP-1 expression in subcutaneous adipose tissue.
Conclusion: In obese mice, TERN-501 significantly improved the efficacy of a GLP-1R agonist by normalizing EE, resulting in greater weight loss, increased fat mass loss, and relative preservation of lean mass. These results suggest that TERN-501, a potent and highly selective THRβ agonist, may be an ideal combination partner for GLP-1 therapies.

Disclosure
C. Jones: Employee; Terns Pharmaceuticals. O. Osborn: None. K.P. Quinn: None. M. Feigh: Employee; Gubra. A. Madsen: None. J.R. Jasper: Employee; Terns Pharmaceuticals. Advisory Panel; Rubedo Life Sciences.
764-P: Discovery of ASC30, a Highly Potent and Orally Available Novel Nonpetide GLP-1 Receptor Biased Agonist
Authors: JASON WU JINZI 
Published: June 2024

Introduction & Objective: Injectable peptidic GLP-1 receptor (GLP-1R) agonists are established treatments for Type 2 Diabetes Mellitus (T2DM) and obesity. An nonpeptide oral GLP-1R agonist without injection and cold chain storage offers many benefits for patients. Here we report the discovery of ASC30, a highly potent and orally available novel nonpeptide GLP-1R biased agonist as a potential once-daily oral therapy.
Methods: ASC30 was tested for its activity against GLP-1 receptor by cAMP assay in Flp-In-293-GLP1R cells and for β-arrestin recruitment in cell-based assay. Further, ASC30 was tested in an intravenous glucose tolerance test (IVGTT) in nonhuman primates (NHPs). Orforglipron was used as a reference compound.
Results: ASC30 strongly activated GLP-1R Gαs cAMP pathway with a mean EC50 of 0.011 nM (n=8), compared to a mean EC50 of 0.024 nM (n=8) for orforglipron. Both ASC30 and orforglipron did not induce measurable β-arrestin recruitment signaling (EC50 &gt; 30,000 nM), which indicated both were GLP-1R biased agonists. In IVGTT NHP model, efficacy of ASC30 on insulin secretion, C-peptide secretion and glucose control was compared to orforglipron. With a single i.v. bonus injection of 1.5 mg/kg ASC30 and 6 mg/kg orforglipron, ASC30 stimulated statistically and significantly more insulin secretion than vehicle control (p&lt;0.01) and orforglipron (p&lt;0.05). Further, ASC30 stimulated statistically and significantly more C-peptide secretion than vehicle control (p&lt;0.001) and orforglipron (p&lt;0.01). After a single oral dosing in rats, ASC30’s exposure over 48 hours (AUC0-48h) is 14-fold of that of orforglipron. Overall, ASC30 demonstrated more potent in vitro cAMP activation and more in vivo efficacy in stimulating insulin and C-peptide secretion than orforglipron.
Conclusion: ASC30 is a highly potent and orally available GLP-1R biased agonist. Human clinical trials are warranted to further evaluate ASC30 as a potential oral therapy for T2DM and obesity.

Disclosure
J. Wu: None.
772-P: GLP1RA Use and Risk of Pancreatitis and Biliary Disease in Adults with Type 2 Diabetes and Low to Moderate CV Risk
Authors: PAIK JULIE M. , TESFAYE HELEN , JANE CROMER SARA , DICESARE ELYSE O. , ALIX CAROLINE , WEXLER DEBORAH J. , PATORNO ELISABETTA 
Published: June 2024

Introduction & Objective: Glucagon-like peptide-1 receptor agonists (GLP1RA) may increase pancreatitis and biliary disease risk. We investigated the association between GLP1RA initiation and the risk of pancreatitis or biliary disease among patients with type 2 diabetes (T2D) at low-to-moderate cardiovascular (CV) risk, a population that remains largely unexplored in clinical trials.
Methods: We estimated hazard ratios (HRs), rate differences (RD) and 95% confidence intervals (CI) of acute pancreatitis or biliary disease among 1:1 propensity score-matched adults initiating GLP1RA vs. dipeptidyl peptidase-4 inhibitor (DPP4i) or sodium glucose cotransporter 2 inhibitor (SGLT2i) in Medicare and 2 private health plans (2013-2023).
Results: Over a mean follow-up of ~11 months, the HR for pancreatitis in the GLP1RA group was 1.19 (95%CI 1.00-1.42; RD 0.20 per 1,000 person-years (PY) [0.01-0.39]) compared with the DPP4i group and 0.99 (0.82-1.20; RD -0.01 per 1,000 PY [-0.17-0.16]) compared with the SGLT2i group (Table). The HR for biliary disease in the GLP1RA group was 1.10 (0.96-1.26; RD 0.13 per 1,000 PY [-0.10-0.37]) compared with the DPP4i group and 1.12 (0.97-1.30; RD 0.22 per 1,000 PY [0.01-0.43]) in the SGLT2i group.
Conclusion: GLP1RA initiation was not associated with meaningful differences in the risk of acute pancreatitis or biliary disease in patients with T2D and low-to-moderate CV risk.

Disclosure
J.M. Paik: None. H. Tesfaye: None. S. Cromer: Other Relationship; Johnson & Johnson Medical Devices Companies. Advisory Panel; Alexion Pharmaceuticals, Inc. Other Relationship; Wolters Kluwer Health. E.O. DiCesare: None. C. Alix: None. D.J. Wexler: Other Relationship; Novo Nordisk. E. Patorno: Research Support; Boehringer-Ingelheim, Food and Drug Administration (FDA), National Institutes of Health, Patient-Centered Outcomes Research Institute.

Funding
Patient Centered Outcomes Research Institute (DB-2020C2-20326)
773-P: Trends in Obesity Drug Initiation after the Approval of Tirzepatide in Adults without Type 2 Diabetes
Authors: PAIK JULIE M. , ORTEGA-MONTIEL JANINNE , TESFAYE HELEN , ALIX CAROLINE , DICESARE ELYSE O. , JANE CROMER SARA , WEXLER DEBORAH J. , PATORNO ELISABETTA 
Published: June 2024

Introduction & Objective: Tirzepatide was approved for the treatment of type 2 diabetes (T2D) (May 2022) and more recently for obesity (November 2023). However, tirzepatide has been used off-label for the treatment of obesity in adults without T2D prior to November 2023. The utilization trends and uptake among adults without T2D is unknown.
Methods: Using a US commercial claims database, we identified adults without T2D who initiated anti-obesity drugs between 1/2021 and 6/2023 and 1) plotted monthly drug initiation trends before and after tirzepatide approval for T2D (May 2022), and 2) compared the uptake of tirzepatide to the historical uptake of other GLP-1RA during their first 13 months after FDA approval.
Results: From 1/2021 to 6/2023, semaglutide initiation decreased (from 26.9% to 23.5%), whereas tirzepatide use increased dramatically (from 0.3% to 45.4%) (Figure A). Compared with the uptake of other GLP-1RA drugs among patients without T2D during their first 13 months after FDA approval, the uptake of tirzepatide was steep and sustained (Figure B). All other medications were initiated less frequently, with liraglutide and phentermine experiencing notable declines after the approval of tirzepatide.
Conclusion: Off-label use of tirzepatide increased sharply among adults without T2D during its first 13 months on the market, even though it was not approved for the treatment of obesity until November 2023.

Disclosure
J.M. Paik: None. J. Ortega-Montiel: None. H. Tesfaye: None. C. Alix: None. E.O. DiCesare: None. S. Cromer: Other Relationship; Johnson & Johnson Medical Devices Companies. Advisory Panel; Alexion Pharmaceuticals, Inc. Other Relationship; Wolters Kluwer Health. D.J. Wexler: Other Relationship; Novo Nordisk. E. Patorno: Research Support; Boehringer-Ingelheim, Food and Drug Administration (FDA), National Institutes of Health, Patient-Centered Outcomes Research Institute.
774-P: Impact of Newer GLP-1 RAs on HbA1c in U.S. Adults with Type 2 Diabetes—A Population-Level Time-Series Analysis
Authors: LV LEI , WANG YAN , XIE LIN , NOONE JOSHUA , ALVAREZ SARA B. , ZHANG YUEHAN , SONG YAN , ROTROFF DANIEL M. 
Published: June 2024

Introduction & Objective: It is unclear whether glucagon-like peptide 1 receptor agonist (GLP-1 RA) treatments improve population-level diabetes-related outcomes. This study examined the impact of GLP-1 RA uptake on population-level HbA1c in US adults with type 2 diabetes.
Methods: This retrospective study used data from the Optum Clinformatics® Data Mart (01/2004-12/2022). Time series regressions were used to examine associations between HbA1c-related outcomes and the proportion of patients on newer GLP-1 RAs of interest (dulaglutide, once-weekly or oral semaglutide, and tirzepatide). Interrupted time series analyses were used to assess temporal trends in population-level HbA1c outcomes. Both analyses were adjusted for potential confounders.
Results: With more patients taking newer GLP-1 RAs, average population-level HbA1c decreased significantly (at 7-9 months of lag), and the proportion of patients with HbA1c &lt;7% increased significantly (at 5-9 months of lag; Fig 1A). Interrupted time series analyses (Fig 1B-C) showed that average HbA1c decreased and the proportion of patients with HbA1c &lt;7% increased after the introduction of newer GLP-1 RAs in 2014.
Conclusion: Increased adoption of newer GLP-1 RAs is associated with lower average HbA1c and higher proportion of HbA1c &lt;7% at the population level. Population-level HbA1c control was improved after the first newer GLP-1 RA approval.

Disclosure
L. Lv: Employee; Novo Nordisk. Y. Wang: Other Relationship; Novo Nordisk. L. Xie: None. J. Noone: Employee; Novo Nordisk. S.B. Alvarez: Employee; Novo Nordisk. Y. Zhang: Other Relationship; Novo Nordisk. Y. Song: Other Relationship; Novo Nordisk. D.M. Rotroff: Consultant; Novo Nordisk. Research Support; Bayer Inc.
779-P: Clinical Characteristics and Treatment Patterns among Glucagon-Like Peptide Receptor Agonist (GLP-1RA) Users in a U.S. EHR and Claims Linked Database
Authors: GIRGUIS MARIAM S. , LILLIE MARK , BODNER ERIC , KASRAI CORDIE K. , SPENCER JESSICA R. , PAULA CANCINO NUNEZ ANA , O'KELLY JAMES 
Published: June 2024

Introduction & Objective: Certain glucagon-like peptide receptor agonists (GLP-1RA) are indicated in different formulations for the treatment of obesity and diabetes. The study objective was to describe real-world demographics, clinical characteristics, and treatment patterns among GLP-1RA users by indication (type 2 diabetes mellitus [T2DM] and chronic weight management [CWM]).
Methods: This was a descriptive retrospective cohort study using Optum’s Market Clarity database, which has linked EHR and claims data. Patients with ≥1 prescription for GLP-1RAs of interest (semaglutide and liraglutide) between 2010 and 2020 were included in the cohort if they had at least 90 days of enrollment/clinical activity prior to index and 365 days of follow-up. Analyses were stratified by GLP-1RA indication.
Results: There were 517,876 GLP-1RA users identified, 473,355 for T2DM and 44,521 for CWM. BMI was similar, while CWM patients were younger, more likely to be female, and have lower prevalence of certain comorbidities compared to T2DM patients (Table). GLP-1RA duration differed by indication for use ≥6 months (T2DM: 46%, CWM: 28%) and &gt; one year (T2DM: 29%, CWM: 13%).
Conclusion: Real-world patients using GLP-1RAs for T2DM and CWM have comparable BMI despite differences in age, sex, and clinical characteristics. Duration of GLP-1RA use is short in clinical practice.

Disclosure
M.S. Girguis: Employee; Amgen Inc. M. Lillie: Employee; Amgen Inc. E. Bodner: None. C.K. Kasrai: None. J.R. Spencer: None. A. Cancino Nunez: Employee; Novo Nordisk. Stock/Shareholder; Novo Nordisk. Employee; Amgen Inc. Stock/Shareholder; Amgen Inc. J. O'Kelly: Employee; Amgen Inc. Stock/Shareholder; Amgen Inc.
790-P: The Effect of Tirzepatide vs. Placebo on Changes and Shifts in BMI Category in Adults with Type 2 Diabetes—A Post Hoc Analysis of the SURMOUNT-2 Study
Authors: GALINDO RODOLFO J. , LAZARUS ETHAN , WANG HUI , GARCIA-PEREZ LUIS-EMILIO , ZHANG MICHELLE X. , GRANT GARY , MALIK RALEIGH 
Published: June 2024

Tirzepatide (TZP) is a GIP and GLP-1 receptor agonist indicated as an adjunct to a reduced-calorie diet and increased physical activity for chronic weight management in adults. The SURMOUNT-2 (SM-2) trial demonstrated significant reductions in body weight in participants treated with TZP with a BMI ≥27 kg/m2 and T2D. This subgroup analysis explored changes in BMI during the SM-2 trial. Prespecified subgroup analyses were conducted on the mITT population in the SM-2 trial to assess the effects of weekly treatment (TZP 10 or 15 mg vs placebo (PBO)) on change from baseline in BMI category at week 72. Table shows shifts in BMI category from baseline to week 72. At Week 72, TZP 10 and 15 mg each resulted in statistically significant reductions in BMI from baseline versus PBO (-4.87 and -5.66 versus -1.18 kg/m2 respectively, p&lt;0.001). For TZP 10 mg and 15 mg arms, 64.7% and 69.5% of participants shift down at least one BMI category, versus 20.9% for PBO. A normal BMI (&lt;25kg/m2) at endpoint was achieved by 18.0% of participants in the 15 mg, and 12.2% in the 10 mg TZP arm compared with 1.9% for PBO. The most common adverse reactions were GI across subgroups, consistent with the results of SM-2.
In conclusion, participants on TZP had significant mean reductions in BMI from baseline and a greater proportion of participants treated with TZP shifted to a lower BMI category compared with PBO.

Disclosure
R.J. Galindo: Consultant; Abbott. Other Relationship; Dexcom, Inc. Consultant; Bayer Inc. Other Relationship; Novo Nordisk, Eli Lilly and Company. Consultant; Boehringer-Ingelheim, AstraZeneca. E. Lazarus: Speaker's Bureau; Novo Nordisk, Eli Lilly and Company. H. Wang: None. L. Garcia-Perez: Employee; Eli Lilly and Company. Stock/Shareholder; Eli Lilly and Company. M.X. Zhang: Employee; Eli Lilly and Company. Stock/Shareholder; Eli Lilly and Company. G. Grant: Employee; Eli Lilly and Company. Stock/Shareholder; Eli Lilly and Company. R. Malik: Employee; Eli Lilly and Company. Stock/Shareholder; Eli Lilly and Company.

Funding
Eli Lilly and Company