GlaxoSmithKline Research Articles

Remineralization Effect of Bioactive Glass With and Without Fluoride and Casein Phosphopeptide-Amorphous Calcium Phosphate (CPP-ACP) on Artificial Dentine Caries: An In Vitro Study.

Background/objectives Dentine hypersensitivity (DH) is a common dental condition marked by transient, sharp pain arising from dentinal exposure. Bioactive materials are capable of remineralization. This study aims to explore the remineralization effect of bioactive glass (BAG) with and without fluoride and casein phosphopeptide-amorphous calcium phosphate (CPP-ACP), using dentine discs as the test substrate. Materials and methods In this in vitro experimental study, 28 dentine discs were prepared from premolar teeth. Artificial caries were induced by subjecting the dentine discs to demineralization in acid for 72 hours. After demineralization, the discs were treated with various remineralizing dentifrices to evaluate their effects. The dentine discs (n=28) were divided into four groups: group 1 = BioMin (BioMin Technologies, London, United Kingdom), group 2 = NovaMin/Sensodyne Repair (GlaxoSmithKline plc, London, England, United Kingdom), group 3 = Recaldent (CPP-ACP; GC Orthodontics Inc., Alsip, Illinois, United States), and group 4 = deionized water (control group). All discs underwent a 28-day remineralization process using the respective dentifrices assigned to each group. The microhardness of the discs was measured using Vickers microhardness testing at three stages: baseline, post-demineralization, and post-remineralization. Results There was no significant difference in terms of microhardness between groups both at the baseline (F (3, 24) = 1.079, p = 0.995) and after the demineralization process (F (3, 24) = 1.310, p = 0.294). However, a significant difference was identified between the groups after the remineralization process (F (3, 24) = 34.008, p = 0.001). Additionally, the least significant difference (LSD) multiple comparison test was performed. There were significant differences identified in the remineralization condition, with group 1 having the highest values, followed by group 2, group 3, and group 4. Conclusion The results indicate that the remineralization effect on artificially induced dentine caries was more pronounced with bioactive glass containing fluoride compared to bioactive glass without fluoride and CPP-ACP.

Re-emergence of Oropouche virus between 2023 and 2024 in Brazil: an observational epidemiological study

Oropouche virus is an arthropod-borne virus that has caused outbreaks of Oropouche fever in central and South America since the 1950s. This study investigates virological factors contributing to the re-emergence of Oropouche fever in Brazil between 2023 and 2024. In this observational epidemiological study, we combined multiple data sources for Oropouche virus infections in Brazil and conducted in-vitro and in-vivo characterisation. We collected serum samples obtained in Manaus City, Amazonas state, Brazil, from patients with acute febrile illnesses aged 18 years or older who tested negative for malaria and samples from people with previous Oropouche virus infection from Coari municipality, Amazonas state, Brazil. Basic clinical and demographic data were collected from the Brazilian Laboratory Environment Management System. We calculated the incidence of Oropouche fever cases with data from the Brazilian Ministry of Health and the 2022 Brazilian population census and conducted age-sex analyses. We used reverse transcription quantitative PCR to test for Oropouche virus RNA in samples and subsequently performed sequencing and phylogenetic analysis of viral isolates. We compared the phenotype of the 2023-24 epidemic isolate (AM0088) with the historical prototype strain BeAn19991 through assessment of titre, plaque number, and plaque size. We used a plaque reduction neutralisation test (PRNT50) to assess the susceptibility of the novel isolate and BeAn19991 isolate to antibody neutralisation, both in serum samples from people previously infected with Oropouche virus and in blood collected from mice that were inoculated with either of the strains. 8639 (81·8%) of 10 557 laboratory-confirmed Oropouche fever cases from Jan 4, 2015, to Aug 10, 2024, occurred in 2024, which is 58·8 times the annual median of 147 cases (IQR 73-325). Oropouche virus infections were reported in all 27 federal units, with 8182 (77·5%) of 10 557 infections occurring in North Brazil. We detected Oropouche virus RNA in ten (11%) of 93 patients with acute febrile illness between Jan 1 and Feb 4, 2024, in Amazonas state. AM0088 had a significantly higher replication at 12 h and 24 h after infection in mammalian cells than the prototype strain. AM0088 had a more virulent phenotype than the prototype in mammalian cells, characterised by earlier plaque formation, between 27% and 65% increase in plaque number, and plaques between 2·4-times and 2·6-times larger. Furthermore, serum collected on May 2 and May 20, 2016, from individuals previously infected with Oropouche virus showed at least a 32-fold reduction in neutralising capacity (ie, median PRNT50 titre of 640 [IQR 320-640] for BeAn19991 vs <20 [ie, below the limit of detection] for AM0088) against the reassortant strain compared with the prototype. These findings provide a comprehensive assessment of Oropouche fever in Brazil and contribute to an improved understanding of the 2023-24 Oropouche virus re-emergence. Our exploratory in-vitro data suggest that the increased incidence might be related to a higher replication efficiency of a new Oropouche virus reassortant for which previous immunity shows lower neutralising capacity. São Paulo Research Foundation, Burroughs Wellcome Fund, Wellcome Trust, US National Institutes of Health, and Brazilian National Council for Scientific and Technological Development. For the Portuguese translation of the abstract see Supplementary Materials section.

The comparison of the quality of selected brands of antibiotics in Tanzania sourced from different geographical regions.

The quality of amoxicillin capsules, ceftriaxone for injection, and ciprofloxacin tablets was evaluated to determine whether there is any difference in quality when comparing the country of origin. This was undertaken because it has been claimed that antibiotics manufactured in Europe are of superior quality to those originating from Africa or Asia. Samples of amoxicillin capsules, ceftriaxone for injection, and ciprofloxacin tablets were collected from three randomly selected wholesale pharmacies in each city, namely Arusha, Dar es Salaam and Mwanza, Tanzania. The collected samples of collected brands were subjected to quality control testing as per their respective pharmacopoeial monographs. Amoxil 250 mg capsules (Glaxo Wellcome, Mayenne, France), Rocephin (Roche, Switzerland) and Cipro-Denk 500 (Allphamed Pharbil Arzneimittel GmbH, Gottingen, Germany) were used as reference brands for the other generic brands of amoxicillin, ceftriaxone and ciprofloxacin, respectively. A total of 31 brands (10 different brands of amoxicillin capsules, 9 of ceftriaxone sodium injections, and 12 of ciprofloxacin tablets) were collected from the targeted regions and subjected to quality control testing. All samples of collected brands complied with the requirements of their respective pharmacopoeial monographs. There was no significant difference in quality between brands of amoxicillin capsules, ceftriaxone for injection, and ciprofloxacin tablets manufactured in Africa and Asia against those manufactured in Europe in terms of compliance with the respective pharmacopoeial monographs.

Characterization of Endothelial to Mesenchymal Transition in Air Pollution Mediated Atherosclerosis: Insights from Trajectory Inference and Functional Analyses in Single cell RNA Sequencing Data

Background: Air pollution is the world’s leading environmental risk factor for atherosclerotic cardiovascular disease (ASCVD). Regressive transcriptional reprogramming and transition of cells to primordial states has been identified as a driver of atherosclerosis. Endothelial cell to mesenchymal cell transition (EndoMT) whereby an endothelial cell transforms to a mesenchymal-like cellular phenotype is one such mechanism. However its relevance to air pollution exposure remains uncharacterized. Methods: Male ApoE−/− mice were inhalationally exposed to concentrated particulate matter &lt;2.5μ component (PM2.5) or filtered air (FA, controls) using a Versatile Aerosol Concentration Enrichment System (VACES, 5–6 h/day, 5 d/week for 36 weeks, n = 7/group. PM2.5 concentrations were 70-80 μg/m3 or ~10X ambient levels. Following euthanasia, single-cell RNA-sequencing of aortic cells was performed using the 10-X platform (CA). For all subsequent analyses, aortic cell samples were integrated. Unsupervised clustering (k-NN) and low-dimensional space visualization (UMAP) were performed with a supervised graph method (Minimum Spanning Tree and Principal Curves) to infer and visualize trajectory analysis of novel cell lineages (branching and cell ordering in pseudotime/pseudospace). Functional analyses were carried out by statistical enrichment analysis using Over Representation Analysis (ORA) and Gene Set Enrichment Analysis (GSEA) against databases of Gene Ontologies (GO), Biological Pathways, putative regulatory motifs, proteins, or disease annotations to find over-representation of terms and functions. Pseudotime distribution assessed along exposure groups and cell-types lineages were statistically compared using GLM models. Differential Expression Analysis within lineages and between groups were tested by GLM and GAM models and FDR correction, followed by functional analyses. Results: Comparison of the pseudotime lineage with lineage root node at the endothelial cells revealed a similarity between observed endothelial (EC) to vascular smooth muscle (VSMC) cell transition with the differential transition noted with PM2.5 from FA. This overlap suggests a potential exaggeration of EC to VSMC transition in response to PM2.5 exposure. Differential gene expression profiling upon PM2.5-exposure in EC revealed significant changes in GO terms related to cell differentiation, cell migration, and regulation of cell population proliferation. Specific genes with variable patterns of expression (4481) were identified along the EC to VSMC lineage. KEGG pathway analysis along the lineage revealed enriched pathways including PI3K/Akt signaling pathway, MAPK signaling pathway, and Rap1 signaling pathway which are all implicated in the development and progression of atherosclerosis. Conclusion: Single-cell analysis reveals that chronic exposure to PM2.5 results in the exaggeration of EC to VSMC transition consistent with the EndoMT paradigm that may help explain the acceleration of ASCVD in response to air pollution exposure. Additional analysis of cell specific pathways may provide improved understanding of mechanisms progression of atherosclerosis in response to environmental exposures. NIH: 1R35ES031702-01, R01 HL155450, 3R35ES031702-02S1; Burroughs Wellcome Fund: 1060485. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

P116 Effectiveness and safety of biosimilar etanercept GP2015 in patients with rheumatoid arthritis in the UK: results from the COMPACT study

Abstract Background/Aims COMPACT is a non-interventional, multinational cohort study to evaluate effectiveness, safety and quality of life (QoL) outcomes in patients with rheumatic diseases treated with GP2015, an approved etanercept (ETN) biosimilar, under real-world conditions. Here, we present data from patients in the UK with rheumatoid arthritis (RA) enrolled in the COMPACT study, focusing on those who switched to GP2015 from reference ETN or another biosimilar ETN. Methods The COMPACT study included patients (≥18 years of age) with rheumatic diseases treated with GP2015. This analysis includes patients from the UK diagnosed with RA who were in treatment Group A (patients in clinical remission or low disease activity under treatment with reference ETN or other biosimilar ETN, who switched to GP2015 prior to study enrolment). Effectiveness and QoL outcomes were assessed using Disease Activity Score 28-joint count (DAS28) and health assessment questionnaire-disability index (HAQ-DI), respectively, and are presented up to Week 24. Safety outcomes were assessed, including rates of adverse events (AEs) and serious AEs (SAEs). Results A total of 112 patients with RA who switched to GP2015 from reference ETN or another biosimilar ETN (Group A) were enrolled in the UK. The mean ± standard deviation (SD) age was 62.9 ± 11.3 years and 74.1% of patients were female. The mean ± SD DAS28 score remained unchanged from baseline (2.6 ± 1.3) to Week 24 (2.5 ± 1.6). The mean ± SD HAQ-DI score displayed no major difference between baseline (1.2 ± 0.8) and Week 24 (0.9 ± 0.8). Overall, 67.9% (n = 76) of patients experienced ≥1 AE and 9.8% (n = 11) of patients experienced ≥1 SAE (Table). Conclusion Over 24 weeks of treatment with GP2015, disease activity remained low and stable in patients with RA previously switched from reference ETN or from another biosimilar ETN, with no new safety concerns observed. These results from a cohort of patients with RA treated in the UK are consistent with effectiveness, QoL and safety data reported previously for the total population in the COMPACT study. Disclosure A. Askari: None. C. Both: None. A. Martin: None. D.A. Walsh: Consultancies; Consultancy fees paid to University of Nottingham: Contura International A/S, Glaxo SmithKline, AKL Research and Development Ltd, Consultancy fees paid to University of Nottingham: Pfizer Ltd, Abbvie Ltd, Ely Lilly &amp; Co.Ltd, Galapagos Ltd., Reckitt Benckiser Health Ltd. Honoraria; Speaker fees paid to David Walsh: Irish Society of Rheumatology, Speaker fees paid to University of Nottingham: Medscape International, Pfizer Ltd, Abbvie Ltd. Grants/research support; Grants paid to University of Nottingham: Versus Arthritis, UKRI, NIHR, Nuffield Foundation, Pfizer Ltd, Ely Lilly &amp; Co Ltd, UCB Pharma, Grants paid to University of Nottingham: GlaxoSmithKline Research and Development, Orion Corporation. T. Sheeran: None.

No additional risk of congenital anomalies after first-trimester dydrogesterone use: a systematic review and meta-analysis.

No additional risk of congenital anomalies after first-trimester dydrogesterone use: a systematic review and meta-analysis.

A real-world study of quality of life following treatment with xylometazoline hydrochloride in individuals with common cold.

The common cold is a frequent, acute, and mild upper respiratory human disease. Nasal congestion has been considered the most bothersome symptom in the common cold, impacting quality of life (QoL). Topical decongestants containing steroids benefit QoL in allergic rhinitis, but no published research has assessed the impact of topical decongestants on QoL in the common cold. To evaluate the effects of xylometazoline hydrochloride 0.1% (Otrivin, GSK Consumer Healthcare SARL, Switzerland) for up to 7 days on QoL in participants with nasal congestion associated with the common cold. This was a decentralized, longitudinal, open-label study. The study enrolled 136 participants (⩾18 years) with early symptoms of the common cold, of which 102 were included in the modified intention-to-treat (mITT) population. Within 24 h of study product receipt, participants confirmed a 'plugged nose' and ⩾1 other common cold symptom. Primary endpoints were Wisconsin Upper Respiratory Symptom Survey-21 (WURSS-21) total score, total and individual symptom scores, and total QoL score. Secondary endpoints were additional QoL scores. Exploratory and post hoc analyses included median days to resolution for each QoL factor and analyses of five QoL categories. Consistent improvements in symptoms and QoL were seen in the mITT population. From day 1, improvements were seen in the 'plugged nose' symptom (p = 0.0023), WURSS-21 total QoL score, and all individual QoL scores (p < 0.0001 for all). After the last dose needed, significant improvements were seen in sleep quality (73%), vitality (76%), physical activity (71%), social activity (80%), and sensation (81%). No serious or unexpected adverse events were reported. This study is the first to demonstrate in a real-life setting that treating nasal congestion in adults with xylometazoline hydrochloride 0.1% during the common cold positively impacts QoL factors relevant to daily living [Otrivin: Quality of Life (QoL) Impact in a Real-World Setting; https://clinicaltrials.gov/study/NCT05556148].

Marketing Modernity, Selling Hazeline: A Comparative Study of Indian and Chinese Markets, 1908–1957

AbstractThis article explores how the experiences of colonial modernity were constituted through global advertising by examining the transnational marketing of Hazeline Snow in early twentieth-century India and China. Manufactured by London-based pharmaceutical company Burroughs Wellcome Company (BWC), Hazeline Snow was a globally circulated medical-cosmetic commodity that showcased the advance of colonial modernity in Asia in the early twentieth century. Focusing on the convergences and divergences in the textual and visual representations of gender, beauty, and race in Chinese and Indian Hazeline Snow advertisements, this article illustrates the uneven ways in which capitalism created, disseminated, and adapted to different knowledge systems in distinct colonial contexts. It argues that modern beauty ideals promoted by cosmetics advertising were not simply the diffusion of a hegemonic Western modernity driven by the symbiotic expansion of capitalism and colonialism, but were shaped by the entanglement of global transformations and local conditions, including pre-colonial aesthetic value systems, inter-Asia exchanges, and competition from both local and other colonial actors. As ‘Snows’ became a specific kind of Asian commodity in their own right, the meanings of being modern and being beautiful was no longer the preserve of a specific company or a generalized ‘West’.

OR19-05 Human Induced Pluripotent Stem Cell-derived Granulosa-like Cells From Ligand-based Differentiation Express FOXL2 After Inhibition Of DKK1

Abstract Disclosure: H. Kubo: None. M.M. Laronda: None. Premature ovarian insufficiency (POI) is characterized by the loss of ovarian function prior to an individual reaching the age of 40. POI can have serious ramifications on health, reducing average life expectancy, and can develop from iatrogenic treatments or genetic variants. POI patients can receive hormone replacement therapies (HRTs), but current methods are not dynamic, responsive, or comprehensive. Contrastingly, cell-based therapies have the potential to produce hormones other than estrogen or progesterone and respond dynamically to each patient. Using human induced pluripotent stem cells (hiPSCs) to generate such cell-based therapies may mitigate rejection upon transplantation and allow for personalized therapies for POI patients. Therefore, we propose to differentiate hiPSCs into granulosa like cells (GLCs) that are functionally the same as granulosa cells (GCs), which are responsible for aromatizing androgens into estrogens. One factor critical to steroidogenesis in GCs is FOXL2, which in mice is suppressed by DKK1, a WNT inhibitor. Therefore, we hypothesized that FOXL2 expression and subsequent steroidogenic functions in our GLCs will be influenced by DKK1. To generate GLCs, we treated the cells with WNT agonist CHIR99021 for two days which has been shown to induce the intermediate mesoderm, and then BMP4 and FST for three days to induce the ovarian somatic lineage. We analyzed our cultures for self-renewal (POU5F1), intermediate mesoderm (PAX2, LHX1, WT1), coelomic epithelium (EMX2), genital ridge (GATA4, NR5A1), and GC (FOXL2) markers using qPCR to assess correct lineage commitment. At day 2, we observed approximately 4000-fold induction of PAX2, 20-fold induction of LHX1, 35-fold increase of WT1, 3000-fold induction of GATA4, and 3.5-fold induction in FOXL2 transcript expression. At day 5, we observed 10-fold induction of NR5A1. We also observed a 7000-fold increase of DKK1 at day 2. Addition of Gallocyanine, a DKK1 inhibitor, from days 2 to 5 resulted in induction of FOXL2 protein expression at day 5, captured by immunofluorescence imaging. Analysis of the images showed that Gallocyanine-treated cells were 42.4% positive for FOXL2, while cells untreated were 0.325% positive for FOXL2. This data suggests that DKK1 does suppress FOXL2 expression in these hiPSC-derived GLCs and demonstrates the potential of these cells as a model to investigate mechanisms important to GC development and maintenance. Future steps include testing the steroidogenic abilities of the GLCs and identification of culture conditions needed to maximize steroidogenesis. This work is supported by the NIH/NICHD R01HD104683 (MML), HuBMAP U01HD110336 (MML), Warren and Eloise Batts Endowment (MML), a Debicki Foundation Grant (MML), the Burroughs Wellcome Fund Career Award at the Scientific Interface (MML), Gesualdo Family Research Scholar (MML), and NIH/NCI training grant T32 CA009560 (HK). Presentation Date: Saturday, June 17, 2023

Bioequivalence Study of Salbutamol 400 mg Tablet in Healthy Indonesian Volunteers by Liquid Chromatography Tandem with Mass Spectrometry

This study objective was to determine the bioequivalence of Salbutamol 4 mg Tablet manufactured by PT Kimia Farma Tbk compared to Ventolin® 2x2 mg Tablet manufactured by Glaxo Wellcome Indonesia, in healthy Indonesian volunteer. The pharmacokinetic parameters calculated in this study are AUC0-24, AUC0-inf, Cmax, Tmax, and T1/2. The study was conducted in a randomized, single-dose, open-label, two-way crossover design (2 treatments, 2 periods, and 2 sequences) under fasting state with 7 (seven) days washed-out period. The number of subjects who participated in the study were 24 volunteers ((12 males and 12 females). The participants were provided with an overview of the study and signed the informed consent form. The study participants underwent a minimum 8-hour fasting period prior to receiving both the test drug and the reference drug, and blood samples were collected at 14 specified time points: 0 hours (before drug administration), minutes-20, minutes-40, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, and 24 hours after drug administration. Plasma concentrations of the drug were determined by LCMS/MS method. The acceptance criteria for the bioequivalence test are 80.00 - 125.00% for AUC0-t and Cmax with 90% Confidence Interval (CI) with α = 5.00%. The mean SD value of AUC0-24, AUC0-inf, Cmax, Tmax, and T1/2 respectively for test drug is 84.49 ±18.99 ng.mL-1.hour; 89.66 ±21.29 ng.mL-1.hour; 13.85 ±4.25 ng/mL; 2.00 ±0.71 hour and 5.08 ±1.27 hour. The mean SD values of AUC0-24, AUC0-inf, Cmax, Tmax, and C1/2 respectively for reference drug are 88.81 ±26.50 ng.mL-1.jam; 93.78 ±27.97 ng.mL-1.jam; 13.39 ±5.39 ng/mL; 2.63 ±1.45 hour and 5.03 ±1.16 hour. Meanwhile, the geometric mean ratio of test drug to reference drug (90% confidence interval) is 96.35% (90.55- 102.53%) for AUC0-24 and 105.39% (93.62-118.65%) for Cmax. Based on the AUC0-24 and Cmax values, Salbutamol 4 mg Tablet manufactured by PT Kimia Farma Tbk is bioequivalent to Ventolin® 2x2 mg Tablet manufactured by Glaxo Wellcome Indonesia.

280-LB: Efficacy of a Respiratory Syncytial Virus (RSV) Prefusion F Protein Vaccine (RSVPreF3 OA) in Older Adults with Preexisting Medical Conditions

Background: Adults with diabetes and other conditions are at increased risk of severe RSV disease and hospitalization. In a phase 3 placebo-controlled study (NCT04886596) in adults ≥60 years, RSVPreF3 OA showed 82.6% vaccine efficacy (VE) against RSV-related lower respiratory tract disease (RSV-LRTD) and 71.7% against RSV-related acute respiratory infection (RSV-ARI). We assessed VE among participants with different BMI and with selected pre-existing metabolic or endocrine conditions (eg, diabetes) that increase the risk of severe RSV disease. Methods: Adults ≥60 years were 1:1 randomized to receive 1 dose of RSVPreF3 OA or placebo before the RSV season. VE against first occurrence of RSV-LRTD and RSV-ARI was calculated for different subgroups (Table). Results: In total, 24,966 participants received RSVPreF3 OA (12,467) or placebo (12,499). Of these, 25.7% (RSVPreF3 OA) and 25.9% (placebo) had ≥1 metabolic or endocrine condition (22.9% diabetes). Mean BMI in both groups was 29.1 kg/m2. In participants with overweight/obesity, VE was 85.6% (RSV-LRTD) and 76.3% (RSV-ARI). In those with ≥1 metabolic or endocrine condition, VE was 100% (RSV-LRTD) and 79.4% (RSV-ARI) (Table). Conclusion: RSVPreF3 OA is highly efficacious against RSV-LRTD and RSV-ARI in adults ≥60 years with overweight/obesity and in those with ≥1 metabolic or endocrine condition. Disclosure R. G. Feldman: Research Support; GSK, Speaker's Bureau; Amgen Inc., GSK. V. Hulstroem: Employee; GlaxoSmithKline plc., Stock/Shareholder; GlaxoSmithKline plc. R. Antonelli incalzi: None. K. Steenackers: Employee; Johnson &amp; Johnson Medical Devices Companies. D. Lee: None. L. Fissette: Employee; GlaxoSmithKline plc., Stock/Shareholder; GlaxoSmithKline plc. M. David: Employee; GlaxoSmithKline plc., Stock/Shareholder; GlaxoSmithKline plc. C. Maréchal: Employee; GlaxoSmithKline plc., Stock/Shareholder; GlaxoSmithKline plc. L. Kostanyan: None. M. Van der wielen: Employee; GlaxoSmithKline plc. Funding GlaxoSmithKline Biologicals SA

524-P: Knowledge, Attitudes, and Perceptions of Respiratory Syncytial Virus (RSV) among U.S. Adults with Diabetes

Rationale: Risk of complications and severe outcomes from respiratory syncytial virus (RSV) infection is increased in older adults and adults with certain chronic conditions in the United States (US). Among adults with diabetes, RSV hospitalization rates are ~2.4-11.4 times higher vs. adults without diabetes. Despite this burden, there are no previous evaluations of RSV knowledge, attitudes, and perceptions (KAP) among adults with diabetes. This study assessed RSV-related KAP among adults at risk of RSV infection, including adults with diabetes. Methods: A cross-sectional, web-based survey of US adults aged 18-89 years was administered between May-June 2022 to evaluate respiratory infection and RSV-related KAP. Target survey sample sizes included ≥200 adults from 4 subgroups: adults aged 18-59 years with diabetes, ≥1 chronic pulmonary, or ≥1 cardiac condition, as well as older adults aged 60-89 years. Results: A total of 339 adults aged 18-89 years with diabetes completed the survey (41.0%; n=339/827). Among those with diabetes, 78.2% (n=265/339) reported being knowledgeable about respiratory infections, although &amp;gt;60% (n=206/339) had never heard of RSV. Among those aware of RSV, 69.9% (n=93/133) rarely consider RSV as a cause of their cold/flu-like symptoms. Examples of identified knowledge gaps included respiratory infection causes (bacterial vs. viral), RSV seasonality, frequency of occurrence, and symptoms. Between 28.6-60.4% perceived that their risk of contracting RSV was lower than for 5 other respiratory infections, but only 19.6-38.9% perceived a lower severity of RSV. Conclusions: This study highlights key RSV knowledge gaps and attitudes/perceptions among US adults with diabetes. Given the increased risk of severe RSV-related outcomes among these adults, findings can be used by health care providers to inform their patient education efforts related to RSV disease awareness. Funding: GlaxoSmithKline Biologicals SA (study: 218693/HE-RSV-004 BOD) Disclosure E.La: Employee; GlaxoSmithKline plc., Stock/Shareholder; GlaxoSmithKline plc. S.Bunniran: Consultant; GlaxoSmithKline plc., Stock/Shareholder; Humana. D.Garbinsky: None. M.Reynolds: None. S.Poston: Employee; GlaxoSmithKline plc. L.Harrington: Employee; GlaxoSmithKline plc.

1072-P: Incidence of Inpatient Hypoglycemia by Specialty Area—A Case for Targeted Inpatient CGM

Inpatient hypoglycemia is traumatic for people with diabetes and increases length of stay, hospital costs and subsequent mortality (at least in the elderly). We report inpatient hypoglycemia by specialty ward in an 800-bed, acute hospital serving a largely deprived population (350,000) with diabetes prevalence 8%. Over 1 year, 21,089 inpatients with diabetes had 176,603 point of care (POC) tests (median 8.4, ward range 1.1-29.2, POC tests/person/stay); and 9.2 (ward range 2.1-24.7)% of subjects experienced hypoglycemia (CBG &amp;lt;72 mg/dl). Patients who experienced hypoglycemia had 2.6 (range 1.2-5.8) episodes of hypoglycemia either from early persistence (failure of protocol-driven hypoglycemia treatment) or late recurrence. There was a strong correlation between POC testing frequency and detection of hypoglycemia (Chi-square, Yates’ correction = 8.4374, p=0.004). Compared with the whole hospital (index 1.0), specialty wards hypo index ranged 10-fold from 0.2 to 5.1. A recent RCT demonstrated CGM superiority over POC testing in preventing recurrent inpatient hypoglycemia. Consistent with this RCT, our data suggest that increased POC testing is associated with increased hypoglycemia detection and our approach might guide initial targeting of CGM to highest risk specialty wards for hospitals unable to deploy CGM simultaneously in every inpatient specialty ward area. Disclosure G.A.Lewis: None. J.Cardwell: None. S.Bujawansa: Stock/Shareholder; Merck &amp; Co., Inc., GlaxoSmithKline plc. K.J.Hardy: Other Relationship; Sanofi, Speaker's Bureau; Napp Pharmaceuticals Limited.

1359-P: Gaps in the Use of Evidence-Based Diabetes Medications for NASH

Patients with type 2 diabetes (T2D) and nonalcoholic steatohepatitis (NASH) are at exceedingly high risk of NASH progression to cirrhosis and end-stage liver disease. T2D medications shown to improve histologic features of NASH, such as GLP-1 receptor agonists and pioglitazone, should be considered for use in all patients with T2D and NASH, unless contraindications exist. However, utilization of T2D medications that benefit NASH are poorly understood. Our objective was to address this gap by examining their use in patients with T2D and NASH engaged with Primary and/or Endocrinology care in the Duke University Healthcare System between 1/1/2019 and 1/1/2021. T2D and NASH were defined by ICD-10 codes, E11.xx and K75.81, respectively and 848 patients were included in the analyses. Mean age of our cohort was 60 (SD 12) years, 62% were female (n=525), 13% (n=110) were Black race and 4.7% (n=40) were Hispanic ethnicity. The mean HbA1c was 7.5% (SD 1.5), and the majority followed with Endocrinology (58.5%, n=496) and used insulin (62.4%, n=529). Only 26.3% (n=223) had an appointment with Duke Hepatology during the study period (either new consultation or follow-up visit). The use of evidence-based T2D medications for NASH was low (34.8%, n=295), with only 31.3% (n=265) and 6.5% (n=55) of patients having been prescribed a GLP-1 receptor agonist or pioglitazone during the study period, respectively. Prescriptions of these medications did not significantly vary by race (Black vs. White unadjusted OR 1.08, 95% CI 0.71, 1.64) or Hispanic ethnicity (unadjusted OR, 1.46, 95% CI 0.77, 2.79). In summary, we observed a large gap between recommended and current use of evidence-based medications for NASH in patients with T2D. Use of pioglitazone was particularly low, despite its low cost and longstanding evidence for use in NASH. Future studies should explore reasons for underuse of these evidence-based T2D medications in NASH, and whether this is changing over time with growing evidence supporting their use in NASH. Disclosure A. Alexopoulos: None. A. Parish: None. M. Olsen: None. B. Batch: Advisory Panel; LLENA (AI). C.A. Moylan: Advisory Panel; Boehringer Ingelheim Inc. Research Support; GlaxoSmithKline plc. M.J. Crowley: None. Funding National Institutes of Health (KL2TR002554)

1380-P: Heterogeneity in the Association of Diet and Obesity in Asian, Pacific Islander, and Multiracial People

Background: Disaggregation of Asian, Pacific Islander (PI), and multiracial API people is needed to assess the subgroup-specific impact of diabetes. This study examined the association between diet quality and obesity. Methods: We used CVD case-control data from two integrated healthcare systems. Diet was measured using the Rapid Eating and Activity for Patient Survey. Results: Among all groups, Native Hawaiians had the lowest mean diet quality while Asian Indians had the highest diet quality (Table 1). Better diet was associated with lower odds of obesity in all groups except Japanese, Native Hawaiian, Other PI, and some multiracial groups after adjustment (Table 2). Conclusion: For some race groups better diet quality was associated with lower odds of obesity. Future work should examine groups where this was not the case. Disclosure S.L.Gibbs: None. A.M.Bacong: None. T.B.Frankland: Research Support; Pfizer Inc., Stock/Shareholder; AbbVie Inc., Pfizer Inc., CVS Health Corp, Regeneron Pharmaceuticals Inc. J.Li: None. Y.G.Daida: Research Support; GlaxoSmithKline plc. L.Palaniappan: None. S.P.Fortmann: Research Support; Pfizer Inc. Funding National Heart, Lung, and Blood Institute (R01HL126172)

747-P: Duration of Sustained Weight Loss in Clinical Trials Evaluating Tirzepatide vs. Comparators—An Exploratory Analysis of SURPASS 1–5

Sustained weight loss of ≥5% is highly beneficial in T2D. Here we assess the time spent with weight loss ≥5% in participants with T2D randomized to the GIP/GLP-1 receptor agonist tirzepatide (TZP) vs comparators in SURPASS 1-5. Participants were randomized to TZP (5, 10, or 15 mg) or comparator (placebo in SURPASS 1 and 5, semaglutide (SEMA) 1 mg in SURPASS 2, insulin degludec in SURPASS 3, and insulin glargine in SURPASS 4) with primary treatment durations of 40 or 52 weeks (wks). Continuous time spent with weight loss ≥5% was descriptively analyzed in all participants on treatment without rescue medication, with missing data imputed in this post-hoc analysis. In SURPASS 1-5, 54-88% of T2D participants randomized to all doses of TZP achieved body weight loss of ≥5%. TZP-treated participants experienced longer time with weight loss ≥5% than those randomized to comparators (Table 1). TZP dose-dependently increased time spent with weight loss ≥5% with the greatest durations observed in the 15 mg group (median: 24 and 40 wks in studies of 40 and 52 wks duration, respectively). Whereas, in the SURPASS 2 trial, those randomized to SEMA 1 mg spent a median of 10 weeks with weight loss ≥5%. In conclusion, TZP led to a longer continuous time spent with weight loss ≥5% compared with placebo, SEMA 1 mg, and basal insulins in participants with T2D. Disclosure W.Garvey: Advisory Panel; Boehringer-Ingelheim, Novo Nordisk, Eli Lilly and Company, Merck &amp; Co., Inc., Alnylam Pharmaceuticals, Inc., Fractyl Health, Inc., Inogen, Research Support; Novo Nordisk, Eli Lilly and Company, Epitomee, Pfizer Inc., Neurovalens. R.L.Batterham: Advisory Panel; Novo Nordisk, GlaxoSmithKline plc., Gila Therapeutics Ltd, Pfizer Inc., Consultant; Eli Lilly and Company, Novo Nordisk, Epitomee, Speaker's Bureau; Eli Lilly and Company, Novo Nordisk, GlaxoSmithKline plc. J.Rosenstock: Advisory Panel; Applied Therapeutics Inc., Boehringer Ingelheim Inc., Eli Lilly and Company, Novo Nordisk, Oramed Pharmaceuticals, Sanofi, Zealand Pharma A/S, Intarcia Therapeutics, Inc., Hanmi Pharm. Co., Ltd., Research Support; Applied Therapeutics Inc., Boehringer Ingelheim Inc., Eli Lilly and Company, Merck &amp; Co., Inc., Novartis, Novo Nordisk, Pfizer Inc., Sanofi, Intarcia Therapeutics, Inc. M.Liu: Consultant; Eli Lilly and Company. V.Thieu: None. J.Daly: Employee; Eli Lilly and Company. B.Bergman: Employee; Eli Lilly and Company, Stock/Shareholder; Eli Lilly and Company. Funding Eli Lilly and Company

158-LB: The Effect of Electronic Nudges on Influenza Vaccination Uptake in Older Adults with Diabetes—A Prespecified Analysis of the NUDGE-FLU Trial

Background: Influenza vaccination is associated with reduced risk of all-cause mortality in patients with diabetes mellitus (DM). However, vaccination rates remain suboptimal. Methods: NUDGE-FLU was a nationwide, pragmatic implementation trial among Danish citizens ≥65 years during the 2022/23 influenza season. Households were randomized in a 9:1:1:1:1:1:1:1:1:1 ratio to usual care or 9 different electronic nudge letters. Baseline and outcome data were obtained via nationwide registries. The endpoint was receipt of a seasonal influenza vaccine before Jan. 1, 2023. In this pre-specified sub-study, effect modification by DM status was assessed in a pooled analysis of all intervention arms vs. usual care, and for individual letters. Results: Of 964,870 participants from 691,820 households, 123,974 had DM. During follow-up, 84.2% with DM vs. 81.5% without DM received a vaccine (p&amp;lt;0.001). In the pooled analysis, DM status modified the effect of any electronic letter compared with usual care on vaccine uptake (p=0.030) such that the effect of any letter was attenuated in participants with DM (82.7% vs. 83.0%; difference, -0.23 percentage points; 99.55%CI: -0.94-0.48; p=0.37) vs. without DM (80.0% vs. 79.7%; difference, +0.36 percentage points; (0.07-0.66); p&amp;lt;0.001). In NUDGE-FLU, 2 of the 9 letters (one emphasizing potential cardiovascular benefits of vaccination and a repeated letter) significantly increased vaccine uptake vs. usual care. Point estimates suggested benefits were more pronounced in participants without DM, but no significant interactions were observed in either case (p&amp;gt;0.10). Conclusion: In a pooled analysis, the effect of any electronic nudge was moderately albeit significantly greater in participants without DM. These findings further suggest that the beneficial effects of specific nudges, including repeated messaging and emphasizing cardiovascular benefits, may be more pronounced in participants without DM. Disclosure M. C. H. Lassen: None. J. S. Jensen: None. C. Martel: None. P. Valentiner-branth: None. T. Biering-sørensen: Advisory Panel; Sanofi, Amgen Inc., GlaxoSmithKline plc., Research Support; Sanofi, Amgen Inc., Boston Scientific Corporation, Novo Nordisk, AstraZeneca, Speaker's Bureau; Sanofi, GlaxoSmithKline plc. N. Johansen: None. M. Vaduganathan: Advisory Panel; American Regent, Amgen, AstraZeneca, Bayer AG, Baxter Healthcare, Boehringer Ingelheim, Chiesi, Cytokinetics, Lexicon Pharmaceuticals, Novartis, Novo Nordisk, Pharmacosmos, Relypsa, Roche Diagnostics,, Research Support; American Regent, Amgen, AstraZeneca, Boehringer Ingelheim, Bayer AG, Galmed, Novartis, Bayer AG, Occlutech, Impulse Dynamics, and Roche Diagnostics, Speaker's Bureau; AstraZeneca, Boehringer Ingelheim, Cytokinetics, Novartis, Roche Diagnostics. A. Bhatt: None. D. Midin: None. B. Claggett: Consultant; Corvia, Cardurion, Cytokinetics Inc., Novartis, Intellia. S. I. Samson: Employee; Sanofi. M. Loiacono: Employee; Sanofi. P. Sivapalan: None. Funding Sanofi

751-P: Longer Time Spent in Glycemic Control after Initiating Tirzepatide vs. Comparators—Exploratory Analysis of SURPASS 1–5 Trials

Conventional trials in people with T2D typically report HbA1c at study end as the primary outcome. In SURPASS 1-5 trials, 81-97% of adults with T2D treated with the GIP/GLP-1 receptor agonist tirzepatide (5, 10, or 15 mg) achieved an HbA1c &amp;lt;7.0% at the primary endpoint. Here we report the time spent in glycemic control throughout the duration of each trial. Participants were randomized to tirzepatide (5, 10, or 15 mg) or comparator (placebo in SURPASS 1 and 5, semaglutide 1 mg in SURPASS 2, insulin degludec in SURPASS 3, and insulin glargine in SURPASS 4), with primary treatment durations of 40 or 52 weeks (wks). Continuous time spent with HbA1c &amp;lt;7.0% was descriptively analyzed in all patients on treatment without rescue medication, with missing data imputed, in this post-hoc analysis. Participants on tirzepatide 5, 10, or 15 mg spent longer time with HbA1c &amp;lt;7.0% than comparators. In studies of 40 wks duration, median time spent with HbA1c &amp;lt;7.0% was 32 wks for all tirzepatide doses, 28 wks for semaglutide 1 mg, and 0 wks for placebo. In studies of 52 wks, this was up to 44 wks for tirzepatide, 32 wks for insulin degludec, and 12 wks for insulin glargine. Time spent with HbA1c &amp;lt;7.0% was generally similar across all tirzepatide doses in each study. To conclude, tirzepatide allowed greater continuous time spent with HbA1c &amp;lt;7.0% vs placebo, semaglutide 1 mg, and basal insulins. Disclosure J.Rosenstock: Advisory Panel; Applied Therapeutics Inc., Boehringer Ingelheim Inc., Eli Lilly and Company, Novo Nordisk, Oramed Pharmaceuticals, Sanofi, Zealand Pharma A/S, Intarcia Therapeutics, Inc., Hanmi Pharm. Co., Ltd., Research Support; Applied Therapeutics Inc., Boehringer Ingelheim Inc., Eli Lilly and Company, Merck &amp; Co., Inc., Novartis, Novo Nordisk, Pfizer Inc., Sanofi, Intarcia Therapeutics, Inc. W.Garvey: Advisory Panel; Boehringer-Ingelheim, Novo Nordisk, Eli Lilly and Company, Merck &amp; Co., Inc., Alnylam Pharmaceuticals, Inc., Fractyl Health, Inc., Inogen, Research Support; Novo Nordisk, Eli Lilly and Company, Epitomee, Pfizer Inc., Neurovalens. R.L.Batterham: Advisory Panel; Novo Nordisk, GlaxoSmithKline plc., Gila Therapeutics Ltd, Pfizer Inc., Consultant; Eli Lilly and Company, Novo Nordisk, Epitomee, Speaker's Bureau; Eli Lilly and Company, Novo Nordisk, GlaxoSmithKline plc. M.Liu: Consultant; Eli Lilly and Company. B.Bergman: Employee; Eli Lilly and Company, Stock/Shareholder; Eli Lilly and Company. A.Hemmingway: Employee; Eli Lilly and Company, Stock/Shareholder; Eli Lilly and Company. V.Thieu: None. Funding Eli Lilly and Company

44-LB: The Effect of Substituting Water for Diet Beverages on CGM Metrics in People with Type 2 Diabetes (T2D)—The Study of Drinks with Artificial Sweeteners (SODAS)

Objectives: Diet beverages (DB) are the largest contributor to artificial sweetener intake in the U.S. diet. People with T2D are the highest consumers of DB, tending to consume them in place of added sugar, especially sugar-sweetened beverages. However, there is little evidence on the health impact of habitual DB consumption by people with T2D. To inform this topic we conducted a randomized trial. Methods: The SODAS study is a two-arm parallel trial with a run-in period of 2 weeks and 24 week intervention that randomized 181 adults with T2D (HbA1c 6.5 - ≤ 8.5%), age 35+ years, who were usual consumers of commercial DB to receive and consume either: 1) A commercial DB of choice (24 oz. daily); or 2) Unflavored sparkling or flat bottled water of choice (H2O) (24 oz. daily). Outcomes include measures of clinical diabetes control and mechanisms that may alter clinical risk. Here we report preliminary secondary outcome results from continuous glucose monitor (CGM) metrics. Participants wore a blinded, Abbott Freestyle Libre CGM for 3, 2-week periods (run-in, week 12, week 24). We conducted an intent to treat analysis to assess the between-arm difference in change of CGM metric from baseline-week 12- week 24 via linear mixed regression models. Results: 179 participants will have complete data when study finishes collection in late March 2023, and 166 had provided complete data at the time of analysis. Participants were a mean age of 58 years, and 55% were men. Time in range (TIR, % of readings 70-180 mg/dL) decreased in both arms and at week 24 the mean TIR for DB was 71.3 (SE 2.8) v. 64.3 (SE 2.8) for H2O, difference of means 7.0 (95% CI -0.7, 14.8), P=0.08). Glycemic variability (%CV) was 27.0 (SE 0.8) for DB at week 24 v. 28.7 (SE 0.8) for H2O, difference in means 1.6 (95% CI -3.8, 0.5), P=0.13. Conclusions: Preliminarily, in people with T2D who habitually consumed DB, there were no significant differences in CGM metrics when substituting H20 intake for DB. Disclosure A. Odegaard: None. A. Bantle: None. E. R. Seaquist: Consultant; Zucara Therapeutics. A. Reikes: Other Relationship; GlaxoSmithKline plc. M. A. Pereira: None. Funding National Institute of Diabetes and Digestive and Kidney Diseases (R01DK117028)

1242-P: Obesity Disparities in a Multiracial Sample of Asian American and Pacific Islander (API) Adults

Background: Asians have higher diabetes rates than Non-Hispanic white (NHW) people, despite having lower BMI. Studies on Asians often present monoracial groups. We examined obesity rates among mono- and multiracial APIs. Methods: We examined obesity and other factors by self-reported race using case-control data from two integrated healthcare systems with large API populations. Results: Obesity varied by race, ranging from 8.5% (Chinese) to 53.5% (Other Pacific Islander) (Table 1). Obesity was high for multiracial API. Demographic, behavioral, and clinical factors explained some, but not all the differences in obesity rates (Table 2). Conclusion: Multiracial API people had higher obesity rates than monoracial API and NHW people. Robust data on multiracial people are needed to understand health disparities among this group. Disclosure A.M.Bacong: None. S.L.Gibbs: None. T.B.Frankland: Research Support; Pfizer Inc., Stock/Shareholder; AbbVie Inc., Pfizer Inc., CVS Health Corp, Regeneron Pharmaceuticals Inc. J.Li: None. Y.G.Daida: Research Support; GlaxoSmithKline plc. S.P.Fortmann: Research Support; Pfizer Inc. L.Palaniappan: None. Funding National Heart, Lung, and Blood Institute (R01HL126172)