bluuebunny/crossref_metadata_2025 huggingface dataset:
660-P: Association between Livable Wage and Quality of Life in Adults with Diabetes
Authors: CAMPBELL JENNIFER A. , EGEDE LEONARD E.
Published: June 2023

Background: Livable wage, compared to federal minimum wage, is income required to cover basic needs without outside assistance. There is limited data on the relationship between livable wage and health outcomes in adults with diabetes. This study tested the relationship between livable wage and quality of life in adults with diabetes.

Methods: MEPS data from 2011-2020 were used. Federal minimum wage was based on the federal 2022 level of $7.25. Livable wage was based on the MIT living wage calculator level of $24.16. Both were multiplied by 280 to account for 40 hours per week for 52 weeks. Outcomes were physical component score (PCS) and mental component score (MCS) of the SF-12. Dependent variable was livable wage categorized as: 1) <federal minimum=“” wage=“” (<$15,080);=“” 2)=“” <livable=“” (=livable wage (≥$50,252). Covariates included: demographics, region, education, insurance, and comorbidities. Multiple linear regression was used to test the relationship between living wage and PCS/MCS adjusting for covariates.

Results: Study sample was 20,327, representing 244,622,755 US adults with diabetes. By livable wage category, 64.1% reported wages <federal minimum=“” wage,=“” 22.6%=“” reported=“” wages=“” =livable wage. In unadjusted models, PCS and MCS were 37.5 and 48.5 for < minimum wage; 45.9 and 51.9 for =livable wage. In adjusted models, PCS and MCS were 39.3 and 48.7 for < minimum wage; 43.7 and 52.2 for =livable wage. Differences between groups were statistically significant for PCS and MCS in unadjusted models and only for PCS in fully adjusted models.

Conclusions: These findings show that livable wage is associated with significantly improved physical and mental health, yet 86% of the population are not receiving a livable wage. As the field moves forward to address structural inequalities, emphasis on economic stability via livable wage is critical to optimize patient outcomes.

Disclosure

J.A.Campbell: None. L.E.Egede: None.

Funding

National Institutes of Health (K24DK093699, R01DK118038, R01DK120861, K01DK131319, R01MD013826)
682-P: Intersectionality among Health-Related Social Needs Predicts Poor Mental Health among Youth and Young Adults with Diabetes
Authors: BROWN ANDREA D. , FRONGILLO EDWARD A. , FLORY KATE , LOHMAN MATTHEW , WEI JINGKAI , MENDOZA JASON A. , REBOUSSIN BETH A. , JENSEN ELIZABETH T. , DOLAN LAWRENCE M. , BELLATORRE ANNA , MALIK FAISAL , LIESE ANGELA D.
Published: June 2023

Little is known about how multiple health-related social needs may overlap to contribute to increased risk for poor mental health outcomes among youth and young adults (YYA) with diabetes. This study aims to understand how household food insecurity (HFI) intersects with other health-related social needs to influence poor mental health among YYA with type 1 diabetes (T1D). Analyses included a total of 829 YYA with T1D from the SEARCH Food Security Cohort study. Classification tree analysis was used to identify patterns among 11 health-related social needs, demographic, and socioeconomic characteristics that distinguish between moderate-to-severe and minimal-to-mild depressive symptoms. Health-related social needs included HFI, housing insecurity, need for reliable transportation, and experiences of discrimination. HFI was measured using the USDA Household Food Security Survey Module and experiences of discrimination were measured using the Everyday Discrimination Scale. The outcome of depressive symptoms was assessed using the Center for Epidemiological Studies-Depression (CES-D) scale. Overall, 35.6% reported moderate-to-severe depressive symptoms and 27.6% of YYA with T1D had anxiety symptoms; however, in the food insecure group, 73% and 56% were affected, respectively. Discrimination intersected with HFI among YYA with T1D such that 86% of YYA experiencing greater discrimination and HFI reported moderate-to-severe depressive symptoms (compared to 47% among the food secure group). In those reporting less discrimination, this corresponded to 56% and 17%, respectively. Adding discrimination to the model that included HFI, demographic, and socioeconomic measures improved the prediction accuracy (AUC= 0.71 versus AUC= 0.64). Study findings have implications for interventions to address multiple health-related social needs to decrease mental health problems among YYA with T1D.

Disclosure

A.D.Brown: None. A.Bellatorre: None. F.Malik: None. A.D.Liese: None. E.A.Frongillo: None. K.Flory: None. M.Lohman: None. J.Wei: None. J.A.Mendoza: None. B.A.Reboussin: None. E.T.Jensen: Consultant; Regeneron. L.M.Dolan: None.

Funding

National Institute of Diabetes and Digestive and Kidney Diseases (1R01DK117461-01, 1UC4DK108173); National Institute of General Medical Sciences (T32GM081740)
7-LB: Sodium–Glucose Cotransporter-2 Inhibitors (SGLT2i) Decrease Kidney Oxygen Consumption in Adults with Type 2 Diabetes (T2D)—A Randomized Clinical Trial Using 11C-Acetate Positron Emission Tomography (PET) Imaging
Authors: HESP ANNE , SNEL LARS I.P. , SCHOBER PATRICK , SCHWARTE LOTHAR A. , BOELLAARD RONALD , BJORNSTAD PETTER , VAN RAALTE DANIËL
Published: June 2023

Kidney hypoxia has been proposed as key pathophysiological mechanism in the development of chronic kidney disease, potentially stemming from a mismatch between oxygen delivery and oxygen consumption. SGLT2i are kidney protective drugs that initially lower glomerular filtration rate (GFR). Accordingly, we hypothesized that SGLT2i lower kidney oxygen consumption by reducing GFR and associated tubular workload. Twenty adults with T2D (sex 80% male, age 68±6 years, BMI 30±4 kg/m2, HbA1c 7.5±0.9%, eGFR 76 ± 11 mL/min/1.73m2) received a 4-week treatment with SGLT2i ertugliflozin (ERTU) and matched placebo (PLB) in a randomized, double-blind cross-over study. Participants were treated with metformin and received maximal tolerable dose of an angiotensin receptor blocker. Whole-kidney oxygen consumption (Kmono) was measured by PET using 11C-acetate. GFR was measured by gold-standard iohexol clearance. Tubular sodium transport (TNa) was calculated by kidney sodium load (([arterial Na]*mGFR) - urinary sodium excretion). Kidney efficiency calculated as TNa/ Kmono. GFR was lower during ERTU (94 ± 14 mL/min) vs. PLB (99 ± 15 mL/min) treatment (p=0.02). Kmono was 0.086 ± 0.006 min-1 during ERTU and 0.091 ± 0.009 min-1 during PLB (p<0.01). Kidney sodium load (12.9 ± 1.90 vs 13.7 ± 2.22 mmol/min) and TNa (12.7 ± 1.87 vs 13.6 ± 2.18 mmol/min) were lower during ERTU (p=0.02 for both), while urinary sodium excretion (p=0.1) and TNa/ Kmono remained unchanged (p=0.7). TNa strongly associated with Kmono (r=0.50; p<0.0001).

In conclusion, SGLT2i lowers mGFR, TNa, and kidney oxygen consumption, potentially decreasing hypoxia risk. SGLT2i treatment did not lower overall kidney efficiency, despite the ATP efficiency of cortical sodium transport. Additional data on cortex and medulla-specific oxygen consumption and multiparametric kidney MRI data will be presented at ADA.

Disclosure

A. Hesp: None. L. I. P. Snel: None. P. Schober: None. L. A. Schwarte: None. R. Boellaard: None. P. Bjornstad: Advisory Panel; AstraZeneca. Consultant; Bayer Inc., Bristol-Myers Squibb Company. Advisory Panel; Novo Nordisk, Lilly, Horizon Therapeutics plc, Boehringer Ingelheim (Canada) Ltd., LG Chem. D. van Raalte: Consultant; Boehringer Ingelheim and Eli Lilly Alliance, AstraZeneca, Merck & Co., Inc. Research Support; Boehringer Ingelheim and Eli Lilly Alliance, AstraZeneca, Merck & Co., Inc.

Funding

MSD
724-P: Baseline Findings from ACT1VATE—A Novel RCT for Diabetes Distress
Authors: SORIANO EMILY C. , FORTMANN ADDIE L. , SANDOVAL HALEY , ANTRIM MCKAYLA G. , GUZMAN SUSAN , POLONSKY WILLIAM H. , SPIERLING BAGSIC SAMANTHA R. , PHILIS-TSIMIKAS ATHENA
Published: June 2023

Recent interventions for diabetes distress (DD) have achieved dramatic improvements in DD, but not A1c. Further, none have been rigorously tested in the healthcare settings where individuals receive their diabetes care. An in-progress RCT will compare diabetes education (DSME/S) to an Acceptance and Commitment Therapy group program (ACT1VATE) in improving glycemic management in N = 484 adults with type 1 diabetes, A1c ≥ 8, and significant DD. We predict that ACT1VATE will be superior to DSME/S in improving DD and glycemic management given its 1) goal to change one's relationship with difficult diabetes thoughts/emotions driving problematic health behaviors and 2) linkage of diabetes self-care behavior to one's personal values, thus eliciting intrinsic motivation for meaningful, lasting health behavior changes. Thus far, enrolled participants (N = 105) are predominantly female (65%), non-Hispanic (83%), and employed (63.8%), but heterogeneous in terms of education (49.5% completed college, 26.1% high school or less), household income (24% < $50k, 38% > $100k), and age (20 to 83; M = 45.9±16.1 years). Mean baseline A1c = 9.2±1.4 and Diabetes Distress Scale total = 2.8±0.9 (indicating “moderate/severe” distress). The Acceptance and Action Diabetes Questionnaire (AADQ) measured psychological processes targeted in ACT1VATE (psychological inflexibility, experiential avoidance). Consistent with our theoretical framework, at baseline, greater diabetes acceptance/action (higher AADQ) was significantly correlated with lower A1c (r = -.30) and diabetes distress (r = -.63), fewer missed insulin doses (r = -.38), healthier diet (r = .29) and better overall well-being (r = .55), ps < .01. As the first large scale DD RCT integrated in a real-world setting, this study will build on prior well-controlled efficacy trials and provide rich information about implementation. These findings will inform healthcare systems’ attempts to meet ADA recommendations to integrate DD screenings and interventions into routine care.

Disclosure

E.C.Soriano: None. A.L.Fortmann: Employee; Dexcom, Inc. H.Sandoval: None. M.G.Antrim: None. S.Guzman: Consultant; Abbott Diabetes. W.H.Polonsky: Consultant; Abbott Diabetes, Boehringer Ingelheim and Eli Lilly Alliance, Eli Lilly and Company, Insulet Corporation, Intuity Medical, Inc., MannKind Corporation, Provention Bio, Inc., Sanofi-Aventis U.S., Vertex Pharmaceuticals Incorporated. S.R.Spierling bagsic: None. A.Philis-tsimikas: Advisory Panel; Dexcom, Inc., Novo Nordisk A/S, Sanofi, Other Relationship; Medtronic, Research Support; Novo Nordisk A/S, Lilly, Viking Therapeutics, NIH - National Institutes of Health.

Funding

National Institutes of Health (1R01DK127491)
727-P: Improvement in Psychosocial Functioning of Youth with Diabetes and Their Caregivers with Multiple Social Risk Factors
Authors: REED ALISON , NOYA CAROLINA E. , WAGNER DAVID V. , LIM JENNIFER H. , GLOCKER VIVIEN , BAL KAVENPREET S. , GONZALES GRANADOS MARYSOL , STONE ANNEMARIE , MCGRATH MAUREEN T. , HARRIS MICHAEL A. , LODISH MAYA , WONG JENISE C.
Published: June 2023

Background: Social determinants of health (SDOH) lead to health disparities. Novel Interventions in Children's Healthcare (NICH) is a community-based program for youth with chronic conditions such as diabetes, with a high degree of social risk. We describe changes in depressive symptoms, diabetes distress, and diabetes strengths in youth with diabetes and their caregivers who completed one year in NICH at UCSF.

Methods: NICH participants in this analysis had diabetes and were ≥12 years old. All completed the Patient Health Questionnaire-8 (PHQ-8), Problem Area in Diabetes-Teen (PAID-T), and those ≥14 years completed the Diabetes Strength and Resilience measure for adolescents (DSTAR-Teen) at baseline and one year. Caregivers completed the parent PAID-T (P-PAID-T). Paired t-tests were used to compare scores at baseline and one year when scores for both time points were available.

Results: Participants included 15 youth with type 1 and 1 with type 2 diabetes. Mean age was 15.4 ± 1.6 years, 88% were from historically marginalized racial or ethnic groups, and 94% had public insurance. Families had a mean of 8 ± 4.8 social risk factors at baseline, the most common being educational barriers, mental health needs, and trauma. Mean PHQ-8 scores decreased from 8.4 ± 6.4 at baseline to 4.3 ± 5.4 at one year (p=0.014, n=10). Mean PAID-T scores trended towards decreasing from baseline (70.7 ± 19.8) to one year (58.8 ± 22.9, p=0.24, n=10), and mean P-PAID-T scores significantly decreased from 57.3 ± 17.8 to 45.3 ± 16.8 (p=0.044, n=6). Mean DSTAR-Teen scores increased from 44.6 ± 6.3 to 48.9 ± 8.1 at one year (p=0.065, n=8).

Conclusions: Participation in NICH is associated with fewer depressive symptoms, less caregiver diabetes distress, and a trend towards reduced distress in youth and improved diabetes-specific strengths. Further research on SDOH among underrepresented populations is needed, as interventions mitigating social risk have potential to improve psychosocial outcomes.

Disclosure

A.Reed: None. M.A.Harris: None. M.Lodish: None. J.C.Wong: Research Support; Dexcom, Inc., Tandem Diabetes Care, Inc. C.E.Noya: None. D.V.Wagner: None. J.H.Lim: None. V.Glocker: None. K.S.Bal: None. M.Gonzales granados: None. A.Stone: None. M.T.Mcgrath: None.

Funding

The Leona M. and Harry B. Helmsley Charitable Trust
73-OR: Multiancestry Genetic Clustering of Type 2 Diabetes Loci Highlights the Contribution of Non-European Variants to Disease Heterogeneity
Authors: SMITH KIRK , KIM HYUNKYUNG , WESTERMAN KENNETH E. , HSU SARAH , MANDLA RAVI , SCHROEDER PHILIP H. , MAJARIAN TIM , KAUR VARINDERPAL , FLOREZ JOSE C. , MANNING ALISA , MERCADER JOSEP M. , UDLER MIRIAM
Published: June 2023

To identify potential subtypes of type 2 diabetes (T2D) anchored in genetics but informed by physiology, we previously used a soft clustering method to cluster T2D single nucleotide variants (SNVs) by their associated metabolic traits. The resulting European-based clusters represent likely disease mechanistic pathways. However, ancestry-specific SNVs, phenotype characteristics and prevalence rates suggest that a portion of the T2D’s heterogeneity is population-based, requiring expansion of this work to non-European populations.

We created a semi-automated Bayesian non-negative matrix factorization (bNMF) pipeline to generate new ancestry-specific clusters in European (EUR, 390 SNVs), East Asian (EAS, 326 SNVs) and African (AFR, 172 SNVs), as well as trans-ancestry (TA, 498 SNVs), using up to 89 T2D-related traits. We validated the clusters by replicating their trait associations in the Mass General Brigham Biobank cohort (MGBB, N=62,252).

The new ancestry-specific and TA clusters captured previously identified clusters, as well as novel clusters related to possible mechanisms of insulin resistance. In the 11 TA clusters, 127/498 SNVs were from non-EUR T2D studies, with 87 SNVs not represented in the EUR clusters. In the non-European subset of MGBB (N=8,990), 8 of 10 TA cluster pPS were more strongly associated with T2D compared to the corresponding EUR cluster pPS. We assessed in MGBB whether the proportion of cumulative genetic risk attributed to each cluster differed between sub populations. A significantly higher proportion was attributed to the Lipodystrophy cluster in EAS, to the Obesity cluster in EUR, and to the Liver/Lipid cluster in AFR (all t-test P<10-15).

By expanding our previous clusters to include non-European SNVs, we were able to identify new genetic clusters and improve the predictive ability of cluster pPS. Our results suggest that polygenic processes contribute in different proportions across populations.

Disclosure

K.Smith: None. A.Manning: None. J.M.Mercader: None. M.Udler: None. H.Kim: None. K.E.Westerman: None. S.Hsu: None. R.Mandla: None. P.H.Schroeder: None. T.Majarian: Employee; Vertex Pharmaceuticals Incorporated. V.Kaur: None. J.C.Florez: Consultant; AstraZeneca, Novo Nordisk, Other Relationship; AstraZeneca, Merck & Co., Inc.

Funding

National Institute of Diabetes and Digestive and Kidney Diseases (R03DK131249)
745-P: The Impact of COVID-19 and the Public Health Emergency on the Medicare Diabetes Prevention Program
Authors: JACOBS SARA , HOERGER THOMAS J. , ALLAIRE BENJAMIN T. , AMICO PETER , MARKOVICH PATRICIA , ROMAIRE MELISSA
Published: June 2023

Background: The MDPP has been significantly affected by the COVID-19 public health emergency (PHE). Prior to the PHE, the MDPP was designed as an in-person program delivered to participants in community settings. The Centers for Medicare & Medicaid Services (CMS) moved quickly in March 2020 to waive the in-person requirement for MDPP sessions and allow classes to continue on a virtual basis. CMS also permitted beneficiaries to temporarily pause participation.

Purpose: To examine the impact of the COVID-19 PHE on MDPP suppliers and on beneficiary participation, attendance, and weight loss.

Methods: We analyzed data collected as part of the MDPP evaluation and Medicare claims from April 2018 to December 2021. Results: In the 6 months following the start of the PHE, new enrollment fell to 11 beneficiaries per month, a decrease of 236% from the same period in 2019. In addition, 32% of suppliers had more than half of the MDPP beneficiaries drop out, and 22% of suppliers had more than half of their MDPP beneficiaries pause for at least 30 days. In comparison, in 2019, only 2% of suppliers had more than half of their MDPP beneficiaries drop out, and 8% of suppliers had more than half of their beneficiaries pause. For participants who continued or returned after a pause, the share of virtual sessions increased from <1% prior to March 2020 to 92% in April 2020. Thereafter, the percentage of virtual sessions declined, but the overall percentage still exceeded 50% through December 2021. Among beneficiaries who started in January or February and continued in the program without dropping out or pausing, weight loss is very similar between those that participated in 2019 (6.4%; n=245) compared to those in 2020 (6.5%; n=188). Conclusions: Although the PHE altered the way MDPP sessions were delivered and substantially reduced new enrollment in the program, changes in session delivery mode (e.g., in-person to virtual) did not appear to impact overall weight loss among continuing beneficiaries.

Disclosure

S.Jacobs: None. T.J.Hoerger: Research Support; Gilead Sciences, Inc. B.T.Allaire: None. P.Amico: None. P.Markovich: None. M.Romaire: None.

Funding

Centers for Medicare & Medicaid Services (HHSM-500-2014-0037I/75FCMC18F0003)
756-P: A Phase 1c Evaluation of a Novel GLP-1 Analog Ecnoglutide (XW003) for Weight Loss in Adults with Overweight and Obesity
Authors: WANG GUANG , HU WEI , QIN HONG H. , ZHENG QING , NING JING , MENGYING GUO , BU YUE , JONES CATHERINE , FENAUX MARTIJN , XU SUSAN , JUNAIDI MOHAMMED K.
Published: June 2023

Ecnoglutide (XW003) is a novel, long-acting GLP-1 analog being developed for the treatment of type 2 diabetes and obesity.

We conducted a Phase 1c randomized, double-blind, placebo-controlled study of ecnoglutide, which enrolled 60 nondiabetic adults with BMI 24-35 kg/m2. The study was conducted in China. PK, change in mean body weight and BMI, safety, and tolerability were evaluated. Participants received 1.8 or 2.4 mg ecnoglutide or placebo as once weekly injections for 14 weeks, including dose escalation. This core treatment was followed by an open-label extension of the ecnoglutide groups, for a total duration of 26 weeks.

At baseline, participants had a mean body weight of 84.61 ± 10.44 kg and BMI of 29.53 ± 1.73 kg/m2. After 14 weeks of core treatment, mean weight reduction from baseline was -8.29 ± 0.52 kg in the 1.8 mg ecnoglutide group and -7.24 ± 0.56 kg in the 2.4 mg group, compared to -0.61 ± 0.82 kg for placebo (P<0.0001 vs placebo for both doses). At Week 14, the proportion of participants achieving ≥5% weight loss from baseline was 87.5% (95% CI, 67.6 to 97.3) and 70.0% (95% CI, 45.7 to 88.1) for 1.8 and 2.4 mg ecnoglutide, respectively, and 22.2% (95% CI, 2.8 to 60.0) for placebo. Continued weight reduction was observed until the end of study at Week 26, with a mean percent change from baseline of -15.0% (95%CI, -16.8 to -13.2) and -13.2% (95% CI, -15.3 to -11.1) for 1.8 and 2.4 mg ecnoglutide, respectively. At Week 26, ≥5% weight loss was observed for 94.7% (95% CI, 74.0 to 99.9) of participants in the 1.8 mg group and 100.0% (95% CI, 75.3 to 100.0) in the 2.4 mg group.

At steady state, ecnoglutide showed a mean Cmax of 310 - 468 ng/mL, Tmax of 26 - 29 h, and half-life of 139 - 162 h.

Overall, ecnoglutide was safe and well tolerated. The proportion of participants reporting any AE was similar between cohorts (95.2 to 100% for ecnoglutide vs 90% for placebo). The most frequent AEs were gastrointestinal, including diarrhea and vomiting. No drug-related SAE or drug-related AEs ≥Grade 3 were reported.

Disclosure

G. Wang: None. W. Hu: None. H.H. Qin: Employee; Sciwind Biosciences, Sichuan Anerobic Biotech. Q. Zheng: Employee; Sciwind Biosciences. J. Ning: None. G. Mengying: None. Y. Bu: Employee; Sciwind Biosciences. C. Jones: Employee; Sciwind Biosciences. M. Fenaux: Employee; Sciwind Biosciences. Stock/Shareholder; Terns Pharmaceuticals. S. Xu: Employee; Sciwind. M.K. Junaidi: None.

Funding

Sciwind Biosciences
778-P: Efficacy and Safety of Supaglutide as Add-on to Metformin in Patients with Type 2 Diabetes
Authors: ANWAR DILBAR , BAO YUQIAN , ZHOU YUE , CHEN SI , ZHOU JIAN , LI LIANG , CHENG ZHIFENG , DONG XIAOLIN , SHI XIAOXIA , SU XIUHAI , LI LIPING , WANG HAIFANG , WANG YIHUA , LI SHU , LI QINGJU , LI XING , LIU MING , SUN JIAO , ZHAO NAIQING , YANG YEHONG , MA JIANHUA , LI YIMING , WANG QINGHUA , JIA WEIPING
Published: June 2023

GLP-1 is an incretin hormone with broad pharmacological potential. GLP-1 receptor agonists (GLP-1RA) are successfully in clinical use for T2D and obesity. Several GLP-1-based therapies are in clinical evaluation for treating metabolic diseases. Supaglutide (supa), a novel GLP-1RA, is in late-stage clinical investigation for T2D. The efficacy and safety are being investigated in 340 patients with T2D inadequately controlled on metformin in this randomized, double-blind, placebo-controlled phase 3 clinical trial (NCT04998032). Supa 3 mg QW treatment resulted in a statistically significant reduction in HbA1c of -1.81% from baseline at week 24 (p<0.001). Body weight was decreased by 3.80% from baseline in supa 3 mg group, with a significant difference versus placebo group (p<0.001). Supa also significantly improved glucose excursion, and increased meal-stimulated insulin and C-peptide secretion as determined by MMTT, suggesting improved glucose tolerance and enhanced β-cell function. Overall TEAEs occurred in 66.7% and 73.4% with placebo and supa 3 mg, respectively. The most common TEAEs with supa were GI symptoms, such as nausea, vomiting, diarrhea and decreased appetite mostly in mild or moderate severity. Supa 3 mg improved glycemic and metabolic control and was well tolerated in T2D inadequately controlled on metformin, suggesting supa as a novel alternative therapy for T2D and metabolic disorders.

Disclosure

D.Anwar: None. X.Su: None. L.Li: None. H.Wang: None. Y.Wang: None. S.Li: None. Q.Li: None. X.Li: None. M.Liu: None. J.Sun: None. N.Zhao: None. Y.Bao: None. Y.Yang: None. J.Ma: None. Y.Li: None. Q.Wang: None. W.Jia: None. Y.Zhou: None. S.Chen: None. J.Zhou: None. L.Li: None. Z.Cheng: None. X.Dong: None. X.Shi: None.
784-P: Characteristics of People with Young-Onset T2D in the SURPASS Program
Authors: GALINDO RODOLFO J. , ZEITLER PHILIP , DAVIES MELANIE J. , LEE CLARE , THIEU VIVIAN , NICOLAY CLAUDIA , ALLEN SHERYL , BERGMAN BRANDON
Published: June 2023

Young-onset T2D, defined as diagnosed before age 40, is increasing around the world. Recent data suggest a faster deterioration in beta-cell function and earlier development of complications in this population, compared to later-onset T2D. This post-hoc analysis evaluated the baseline characteristics of people with young-onset vs later-onset T2D in the SURPASS clinical trial program. Baseline demographics and clinical characteristics were compared in participants with young-onset vs later-onset T2D from the SURPASS-1, -2, -3, and -5 clinical trials (N=4267). Analyses were performed by study. Across the SURPASS program, which included participants at various stages of T2D management, participants with young-onset T2D were younger, had longer duration of diabetes, worse glycemic control, higher mean body weight and BMI, and a worse lipid profile at baseline vs patients with later-onset T2D. Data from SURPASS-1 and SURPASS-2 also showed participants with young-onset T2D had greater insulin resistance (HOMA2-IR) at baseline. Despite their younger age at baseline, participants with young-onset T2D in the SURPASS program had an overall worse health status as compared to patients with later-onset T2D. Early intervention in young-onset T2D may be important to optimize long-term outcomes.

Disclosure

R.J.Galindo: Consultant; Novo Nordisk, Eli Lilly and Company, Sanofi, Pfizer Inc., Bayer Inc., WW (Weight Watchers), Research Support; Novo Nordisk, Eli Lilly and Company, Dexcom, Inc. P.Zeitler: Consultant; Eli Lilly and Company, Boehringer Ingelheim Inc., Johnson & Johnson. M.J.Davies: Advisory Panel; Lilly, Boehringer-Ingelheim, Novo Nordisk, Sanofi, Lexicon Pharmaceuticals, Inc., Pfizer Inc., Medtronic, ShouTi Pharma Inc., Consultant; Lilly, Boehringer-Ingelheim, Novo Nordisk, Sanofi, Research Support; AstraZeneca, Novo Nordisk, Sanofi-Aventis U.S., Boehringer-Ingelheim, Janssen Pharmaceuticals, Inc., Speaker's Bureau; Lilly, Boehringer-Ingelheim, Novo Nordisk, AstraZeneca, Napp Pharmaceuticals Limited, Novartis, Sanofi. C.Lee: Employee; Eli Lilly and Company, Stock/Shareholder; Eli Lilly and Company. V.Thieu: None. C.Nicolay: Employee; Eli Lilly and Company. S.Allen: None. B.Bergman: Employee; Eli Lilly and Company, Stock/Shareholder; Eli Lilly and Company.

Funding

Eli Lilly and Company
785-P: Comparative Effectiveness of Second-Line Glucose-Lowering Medications—Emulation of a Target Trial Using Real-World Data
Authors: DENG YIHONG , POLLEY ERIC , WALLACH JOSHUA D. , HERRIN JEPH , ROSS JOSEPH , MCCOY ROZALINA G.
Published: June 2023

The comparative effectiveness of commonly used 2nd-line type 2 diabetes medications with respect to lowering hemoglobin A1c (HbA1c) is unknown, as the GRADE trial did not include a SGLT2 inhibitor arm and was limited to patients with moderately uncontrolled HbA1c. We used claims and laboratory data OptumLabs® Data Warehouse (a de-identified dataset of enrollees in private and Medicare Advantage health plans across the U.S.) between 3/29/13 and 6/30/21 to compare the effectiveness of initiating glimepiride, sitagliptin, liraglutide, canagliflozin, and insulin glargine by adults with type 2 diabetes, treatment-naïve or on metformin monotherapy, with respect to time to HbA1c ≥7.0%. Propensity scores were estimated using the gradient boosting method and inverse propensity score weighting was used to emulate randomization to the treatment groups, which were then compared using Cox proportional hazards regression. Liraglutide initiators had the lowest 1-year cumulative incidence rate of achieving HbA1c ≥7.0% (0.31 [95% CI, 0.27-0.35]) followed by sitagliptin (0.42 [95% CI, 0.40-0.43]), canagliflozin (0.43 [95% CI, 0.40-0.46]), and glimepiride (0.43 [95% CI, 0.42-0.44]); Figure. The glargine arm was excluded due to insufficient control of confounding, reflecting limitations of emulating trials using real-world data if study conditions are not represented in practice.

Disclosure

Y.Deng: None. E.Polley: None. J.D.Wallach: Consultant; Hagens Berman Sobol Shapiro LLP and Dugan Law Firm APLC, Other Relationship; Johnson & Johnson, Research Support; NIH - National Institutes of Health, Arnold Ventures. J.Herrin: Consultant; Johnson & Johnson Medical Devices Companies. J.Ross: Research Support; Johnson & Johnson. R.G.Mccoy: Consultant; Emmi.

Funding

National Institute of Diabetes and Digestive and Kidney Diseases (K23DK114497)
791-P: Comparing the Real-World Effects of Once-Weekly GLP-1 RAs and DPP-4 Inhibitors on Ischemic Stroke and Myocardial Infarction in Individuals with T2D and ASCVD
Authors: TAN XI , LIANG YUANJIE , RAJPURA JIGAR R. , YEDIGAROVA LARISA , NOONE JOSHUA , XIE LIN , DE HAVENON ADAM
Published: June 2023

Despite guidelines advocating for their use, there is limited real-world evidence comparing the effects of once-weekly (OW) glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and dipeptidyl peptidase 4 inhibitors (DPP-4is) on the risk of cardiovascular events in individuals with type 2 diabetes (T2D) and atherosclerotic cardiovascular disease (ASCVD). This retrospective cohort study compared the time to incidence of ischemic stroke, myocardial infarction (MI), and 2-point major adverse cardiovascular events (MACE; ischemic stroke or MI) while on treatment in new adult users of OW GLP-1 RAs and DPP-4is who had T2D and ASCVD using data from the Optum Clinformatics® Data Mart (2017-2021). Patients were followed until drug discontinuation, enrollment end, or an event. Inverse probability of treatment weighting was used to balance baseline characteristics, and survival analyses were conducted to compare risks during exposure, defined as continuous use of either drug. We found that users of OW GLP-1 RAs (weighted N=25,287) had significantly lower risks of ischemic stroke (HR=0.74 [95% CI, 0.63, 0.87]), MI (0.78 [0.67, 0.92]), and 2-point MACE (0.76 [0.68, 0.86]) compared with users of DPP-4is (weighted N=39,684; all P<0.01). This study suggests that OW GLP-1 RAs reduce the risk of MI and stroke relative to DPP-4is in individuals with T2D and ASCVD.

Disclosure

X. Tan: Employee; Merck & Co., Inc. Stock/Shareholder; Merck & Co., Inc. Employee; Novo Nordisk. Stock/Shareholder; Novo Nordisk. Y. Liang: Employee; Novo Nordisk. J.R. Rajpura: Employee; Novo Nordisk. L. Yedigarova: Employee; Novo Nordisk. Stock/Shareholder; AbbVie Inc. J. Noone: Employee; Novo Nordisk. L. Xie: Employee; Pfizer Inc., Novo Nordisk A/S. A. de Havenon: Consultant; Novo Nordisk, Integra Lifesciences Holdings Corp. Other Relationship; UpToDate. Stock/Shareholder; TitinKM, Certus.
824-P: Glycemic Improvement, Insulin Reductions, and Improved Body Weight 48 Weeks after Revita Duodenal Mucosal Resurfacing in T2D patients with Previously Inadequately Controlled Glucose Despite Multiple Glucose-Lowering Agents Including Insulin
Authors: FONSECA VIVIAN , BERGMAN JACQUES , SAEED ZEB I. , RAJAGOPALAN HARITH , SORONDO BARBARA , WHITE KELLY , ZHANG HUI , MINGRONE GELTRUDE
Published: June 2023

Background: Due to the progressive nature of T2D, patients often escalate in disease severity, burden, and complexity. Revita® Duodenal Mucosal Resurfacing (DMR) is a non-pharmacologic, investigational, endoscopic treatment intended to restore normal physiology of the duodenum, a key regulator of metabolic homeostasis. Previous studies to date with >300 patients have shown favorable safety and metabolic efficacy. Here we present initial data from open label phase of a pivotal study designed to improve glycemic control while reducing and/or eliminating insulin treatment burden.

Methods: Inclusion: 21-70yrs, BMI 24-40kg/m2, HbA1c 7.5-9.5%, FPG off insulin ≥180-<270mg/dL, fasting C-peptide ≥0.6 ng/ml, insulin (20-60 U/day) with background glucose lowering agents (GLAs). Prior to procedure, GLAs other than metformin and basal insulin were washed out for ≥8wks followed by 4wk run in. Post DMR, insulin was reinstated if needed by a pre-specified treat-to-target design with preexisting metformin and de novo empagliflozin.

Results: N=9. Median (min, max) baseline characteristics: age 60 (45, 68) yrs, 66.7% male, HbA1c 8.5 (7.6, 9.1)%, C-peptide 1.7 (0.7, 3.2) ng/mL, weight 96 (85, 128) kg, diabetes duration 13 (7, 24) yrs; long-acting insulin dose 33 (20, 60) U/day. No device or procedure related SAEs. Unrelated to DMR procedure, two patients discontinued early. N=7: 48-week median change from baseline (min, max); HbA1c -1.5% (-1.8,-0.4), FPG -82 mg/dL (-104,-48), total body weight -9.3% (-16.8,-2.9). All (7/7) patients reduced insulin dose with 2 patients discontinuing insulin entirely.

Conclusion: Results from open label phase thus far show promising safety and efficacy of Revita DMR and suggest broad metabolic benefit while reducing treatment burden. Further results forthcoming from currently enrolling REVITALIZE-1 study.

Disclosure

V.Fonseca: Consultant; Abbott, Corcept Therapeutics, Eli Lilly and Company, Other Relationship; BRAVO4HEALTH, LLC, Research Support; Fractyl Health, Inc., Stock/Shareholder; Amgen Inc. J.Bergman: Consultant; Endogenex, Fractyl Health, Inc., Digma Medical, Research Support; Endogenex, Fractyl Health, Inc., Digma Medical. Z.I.Saeed: None. H.Rajagopalan: Employee; Fractyl Health, Inc. B.Sorondo: Employee; Fractyl Health, Inc., LG Chem. K.White: Employee; Fractyl Health, Inc. H.Zhang: None. G.Mingrone: Advisory Panel; Fractyl Health, Inc., Board Member; Novo Nordisk, Consultant; Novo Nordisk, Fractyl Health, Inc., ReCor Medical, Inc.

Funding

Fractyl Health, Inc.
831-P: Allogeneic Neo-Islets (NIs), an Immune-Privileged Cellular Therapy for T1DM, Is Safe and Effective in Spontaneously Diabetic Pet Dogs, Reducing Insulin Need by up to 50% over Three Years
Authors: GOOCH ANNA , WESTENFELDER CHRISTOF
Published: June 2023

The purpose of this INAD pilot study was to assess the safety, feasibility and efficacy of NIs in significantly reducing or eliminating a T1DM dog's need for insulin and/or preventing, halting or reversing DM-related damage to a dog's other organs. NIs (3-D organoids made of Mesenchymal Stromal Cells (MSCs) and cultured, partially dedifferentiated islet cells) have been shown preclinically (NOD mouse model) to eliminate the need for exogenous insulin when introduced i.p. Their MSC component provides immune isolation, allowing their allogeneic use without antirejection agents.

Hypothesis: Allogeneically administered NIs would safely, durably, and significantly reduce or eliminate the need for exogenous insulin in spontaneously T1DM dogs, as was found in experimental mice. 6 (4 M, 2 F) spontaneously DM, pet dogs; age 1-12 years were treated under INAD 012-776 and followed 3 years. 2×10e5 NIs/kg bw were introduced under ultrasound guidance to metabolically controlled (blood glucose, triglycerides, thyroid, adrenal functions), sedated animals. Dogs were maintained on insulin as needed, and were followed clinically (CBCs, Chemistry panels, Urinalyses, physical examination, imaging, endocrine function) by the PIs and the dogs’ regular veterinarians.

Results: Over 3 years, daily insulin needs, blood and urine glucose and fructosamine fell significantly in 5 of 6 dogs; renal function, body weights, CBCs, chemistries were unchanged. Urinary protein decreased; no hypoglycemic events, and immune response to NIs were observed; no AEs or SAEs were attributed to NIs. Redosing and dosing strategies are being tested to try to eliminate exogenous insulin need. Allogeneic NIs are safe and durably effective, and has significant translational relevance. Even partial effectiveness protects from end-organ damage and preserves renal function. A successful Pre-IND meeting for NI use in humans has been held.

Disclosure

A.Gooch: Board Member; SymbioCellTech, LLC, Employee; SymbioCellTech, LLC, Stock/Shareholder; SymbioCellTech, LLC. C.Westenfelder: Board Member; SymbioCellTech, LLC., Employee; SymbioCellTech, LLC., Research Support; SymbioCellTech, LLC., Stock/Shareholder; SymbioCellTech, LLC.
834-P: Efficacy and Tolerability of Initial Triple Combination Therapy with Metformin, Dapagliflozin, and Saxagliptin Compared with Conventional Stepwise Add-on Therapy in Drug-Naïve Patients with Type 2 Diabetes—A Randomized, 104-Week, Open-Label, Active-Controlled Trial
Authors: HOON KIM NAM , YOON KIM JI , SUNG MOON JUN , LEE YONG-HO , HEON KWAK SOO , LIM SOO , KYONG MOON MIN , GON KIM SIN
Published: June 2023

Background: Early combination therapy is recommended in type 2 diabetes (T2D) patients with inadequately controlled hyperglycemia to avoid treatment failure and clinical inertia. This study aimed to evaluate the efficacy and tolerability of an initial triple combination with metformin, dapagliflozin and saxagliptin compared with conventional stepwise add-on therapy in drug-naïve patients with T2D.

Methods: This multicenter, randomized, 104-week, open-label trial was conducted at 9 medical centers in South Korea. Eligible patients were aged ≥18 years, inadequately controlled (HbA1c ≥ 8.0% to <11.0%), drug-naïve patients with recent-onset T2D. Eligible participants were randomly assigned (1:1) to triple combination therapy (TCT, 1000mg of metformin, 10mg of dapagliflozin and 5mg of saxagliptin once daily) or conventional stepwise therapy (CST) group. CST was started with metformin followed by glimepiride, and sitagliptin sequentially. The primary outcome was the proportion of patients who achieved HbA1c <6.5% without hypoglycemia, weight gain ≥5% and discontinuation due to adverse events at week 104.

Results: A total of 105 eligible participants were randomly assigned to either TCT or CST groups. 89.6% of participants completed the study and treatment. The primary outcome was achieved in 42.5% of the TCT group and 17.5% of the CST group (p=0.015). The proportion of achieving HbA1c <6.5% at week 104 was 50.0% of the TCT group and 45.0% of the CST group. Hypoglycemia, weight gain >5%, or discontinuation due to adverse events occurred in 14.9% of the TCT group, and 59.2% of the CST group.

Conclusion: Initial combination therapy with metformin, dapagliflozin and saxagliptin effectively lowered HbA1c with higher tolerability compared with conventional stepwise treatment in recent-onset T2D.

Disclosure

N.Kim: None. J.Kim: None. J.Moon: None. Y.Lee: None. S.Kwak: None. S.Lim: None. M.Moon: None. S.Kim: None.

Funding

AstraZeneca Korea Ltd (ESR-15-11420)
839-P: Alpha-1 Antitrypsin Augmentation Therapy in Chronic Pancreatitis Patients Undergoing Total Pancreatectomy and Islet Autotransplantation
Authors: WANG HONGJUN , GOU WENYU , ADAMS DAVID , MORGAN KATHERINE , NIETERT PAUL J. , HIRSCH JASON , STRANGE CHARLIE
Published: June 2023

Stress-induced islet graft loss reduces the efficacy of islet transplants. In this single-center, randomized, double-blind, and controlled clinical trial, we evaluated the safety and efficacy of human alpha-1 antitrypsin (AAT) infusion in chronic pancreatitis (CP) patients undergoing total pancreatectomy and islet autotransplantation (TP-IAT) at the Medical University of South Carolina. Among 48 qualified subjects randomized in a 1:2 (placebo vs AAT) ratio, 43 received TP-IAT. Subjects were given saline or AAT infusion at 60mg/kg weekly for 4 weeks and were followed for 12 months. The primary efficacy endpoint was the islet function measured by the C-peptide area under the curve during a mixed meal tolerance test (MMTT) at Month 12 (M12). Adverse events (AEs) were measured throughout the study. Safety, glycemic control, insulin use, and quality of life (QoL) were compared between groups. Safety evaluation showed no significant differences in the types and severity of participant AEs. The primary efficacy outcome was not significantly different between groups. Baseline characteristics including age, body weight, BMI, HbA1C, etc, were comparable in the randomized populations. The oxygen consumption rate before the transplant was higher in the AAT group. Serum C-peptide (an indicator of islet death) was lower in the AAT group, suggesting less islet injury. AAT subjects trended toward better SF-12 physical QoL and lower insulin use at both 75 and 365 days post-IAT. Despite intensive efforts to get participants to return for the Day 365 MMTT, only 10/14 (71%) in the placebo group and 18/29 (62%) in the AAT group returned for this test. Although we did not observe a statistical difference in islet function using AAT therapy, we gained a better understanding of this patient population. Minimizing numbers of follow-up visits, use of fewer doses of medication with higher doses, and providing travel are all important for future clinical trials in TP-IAT.

Disclosure

H. Wang: None. W. Gou: None. D. Adams: None. K. Morgan: Speaker's Bureau; Johnson & Johnson Medical Devices Companies. P.J. Nietert: None. J. Hirsch: None. C. Strange: None.

Funding

National Institute of Diabetes and Digestive and Kidney Diseases (1R01DK105183, DK120394, DK118529); U.S. Department of Veterans Affairs (I01BX004536 to H.W.)
841-P: Phenomapping-Derived Tool to Personalize Chiglitazar Treatment in Type 2 Diabetes—A Post Hoc Analysis of Randomised Clinical Trials
Authors: HUANG QI , ZOU XIANTONG , JIA WEIPING , JI LINONG
Published: June 2023

﻿Chiglitazar is a peroxisome proliferator-activated receptor (PPAR) pan-agonist showing comparable glucose-lowering efficacy with ﻿sitagliptin ﻿in patients with type 2 diabetes. To identify the subgroup with higher benefits with chiglitazar thus personalizes drug therapy, ﻿a post-hoc analysis using a machine learning algorithm was applied in ChiglitAzar Monotherapy with Placebo (CAMP) and ﻿ChiglitAzar Monotherapy with Sitagliptin (CAMS) study. We constructed a phenomap based on 13 baseline variables from 1069 patients with diabetes assigned to chiglitazar (32mg or 48mg, n=822) and sitagliptin (n=247). Personalized HbA1c decline at week 24 was estimated using least squares regression weighted for phenotypic distances between each participant. High-benefit group (HBG) was defined as patients with estimated HbA1c decline higher in chiglitazar ﻿than sitagliptin, and low-benefit group (LBG) was defined as the opposite.677 (63.3%) patients were allocated to the HBG and 392 (36.7%) were allocated to the LBG.﻿ Chiglitazar showed higher HbA1c decline than sitagliptin In the HBG and lower HbA1c decline in the LBG (relative decline 0.67%, 95%CI [0.50, 0.83] in HBG and -0.93% [-1.18, -0.68] in LBG, p for interaction<0.001). There was no significant inter-group heterogeneity in changes in HOMA-IR, HDL, ﻿triglyceride and body weight. Dosage analysis suggested the majority (n=635, 77.3%) would gain more glucose-lowering benefits from chiglitazar 48mg than 32mg. To facilitate efficient identification of HBG in the clinic, we developed ML-PANPPAR, a machine learning model based on extreme gradient boosting algorithm (XGBoost). The model showed robust performance (AUC=0.933 in the internal testing subset) to recognise HBG with five simple variables including sex, BMI, HbA1c, HDL and fasting insulin.﻿Our phenomapping-derived tool provides support to ﻿select specific patients to receive chiglitazar for better glucose-lowering efficacy.

Disclosure

Q.Huang: None. X.Zou: None. W.Jia: None. L.Ji: Other Relationship; Eli Lilly and Company, Novo Nordisk, Merck & Co., Inc., Bayer Inc., Sanofi-Aventis U.S., Roche Pharmaceuticals, MSD Life Science Foundation, AstraZeneca, Boehringer Ingelheim Inc., Abbott, Metronics.

Funding

Beijing Nova Cross Program (Z211100002121169); Beijing Nova Program of Science and Technology (Z191100001119026 to X.Z.)
843-P: Effects of Pemafibrate on Glucose Metabolism in Adults with Type 2 Diabetes and Hypertriglyceridemia—Subanalysis of the PARM-T2D Study
Authors: NOMOTO HIROSHI , KITO KENICHI , NAKAMURA AKINOBU , KAMEDA HIRAKU , OMORI KAZUNO , YANAGIYA SHINGO , IESAKA HIROSHI , OE YUKI , KAWATA SHINICHIRO , ATSUMI TATSUYA , MIYOSHI HIDEAKI
Published: June 2023

Background and Aims: Pemafibrate, a novel selective peroxisome proliferator-activated receptor modulator, has been demonstrated to have potent effects on abnormalities of lipid metabolism in adults with type 2 diabetes (T2DM) and hypertriglyceridemia in real-world clinical practice (PARM-T2D study). However, the effects of pemafibrate on glucose metabolism have not been fully clarified.

Materials and Methods: In this multicenter, open-labeled, prospective, observational study, adults with T2DM were treated with pemafibrate (PEMA group) or continued on their current therapy (CTRL group) for dyslipidemia for 52 weeks. This subanalysis consisted of participants who did not change their treatment for diabetes and who did not receive insulin or insulin secretagogues during the study period. Glycemic control, insulin secretion, and insulin resistance were assessed by HbA1c levels, HOMA2-β, and HOMA2-R, respectively. The changes of these parameters between baseline and the end of the study were compared between the groups.

Results: In total, 279 of 650 participants met the criteria for this analysis. There were no statistical differences in baseline characteristics between PEMA (n = 141) and CTRL groups (n = 138). There were no significant changes in HbA1c levels and beta-cell function over 52 weeks between the groups, whereas pemafibrate significantly improved insulin resistance assessed by HOMA2-R versus the CTRL group (−0.20 vs. 0.01; estimated treatment difference, −0.23% [95% confidence interval = −0.44, −0.02]; p<0.05). Pemafibrate also ameliorated lipid profiles and liver dysfunction. Changes in serum triglyceride, HDL-cholesterol, γ-GTP, and ALP levels were significantly correlated with those in HOMA2-R (p = 0.024, p = 0.002, p < 0.001, and p = 0.032, respectively).

Conclusions: Pemafibrate reduced insulin resistance and improved lipid profiles and liver dysfunction in individuals with T2DM and hypertriglyceridemia.

Disclosure

H.Nomoto: Speaker's Bureau; Novo Nordisk, Sumitomo Pharma, Co., Ltd. T.Atsumi: Speaker's Bureau; Eli Lilly Japan K.K., Kowa Company, Ltd. H.Miyoshi: Research Support; Abbott, LifeScan Diabetes Institute, Taisho Pharmaceutical Holdings Co., Ltd., Speaker's Bureau; AstraZeneca, Boehringer Ingelheim Japan, Inc., Eli Lilly Japan K.K., Kowa Company, Ltd., MSD Life Science Foundation, Novo Nordisk, Ono Pharmaceutical Co., Ltd., Sanofi K.K., Mitsubishi Tanabe Pharma Corporation. K.Kito: None. A.Nakamura: Research Support; Abbott Japan Co., Ltd., Boehringer Ingelheim Japan, Inc., Daiichi Sankyo, Taisho Pharmaceutical Holdings Co., Ltd., Teijin Pharma Limited, Kowa Company, Ltd., Mitsubishi Tanabe Pharma Corporation. H.Kameda: None. K.Omori: None. S.Yanagiya: None. H.Iesaka: None. Y.Oe: None. S.Kawata: None.