bluuebunny/crossref_metadata_2025 huggingface dataset:
607-P: Associations of Gut Microbiome with Glycemic Control in a Carbohydrate-Restricted, High-Protein Diet for Type 2 Diabetes Mellitus
Authors: HOOPS SUSAN L. , KNIGHTS DAN , BANTLE ANNE
Published: June 2024

Objective: The Low Biologically Available Glucose (LoBAG) diet was designed to improve glycemic control of type 2 diabetes mellitus (T2D). We evaluate changes in the gut microbiome when participants with T2D are given the LoBAG diet.

Methods: Thirty-six participants with T2D taking metformin or no glucose-lowering medication were enrolled in a 12-week randomized controlled trial. Participants were randomly assigned to the LoBAG diet (30% low-starch carbohydrate, 30% protein, 40% fat) or a control diet (50% carbohydrate, 15% protein, 35% fat). Fecal samples were collected at weeks 0, 6, and 12 along with the primary outcome, hemoglobin A1c (HbA1c).

Results: Diet groups were significantly distinct in terms of Bray-Curtis dissimilarity in weeks 6 and 12 following the dietary intervention (p<0.001, PERMANOVA), indicating shifts in the microbiome profile following the diet intervention. In particular, abundance of Firmicutes was lower in the LoBAG diet group (Mann-Whitney U test, p < 0.001). The primary outcome, HbA1c, was significantly more reduced in the LoBAG diet group (t-test, p=0.04, week 12 - baseline) following dietary intervention.

Conclusions: Participants with T2D consuming the LoBAG diet had greater reduction in HbA1c over 12 weeks than those consuming a control diet. This difference was also associated with shifts in the gut microbiome, but further studies are needed to explore a relationship between HbA1c and the gut microbiome.

Disclosure

S.L. Hoops: None. D. Knights: None. A. Bantle: None.

Funding

University of Minnesota Department of Medicine (Faculty Research Award); National Center for Advancing Translational Sciences (UL1TR002494 and KL2TR002492); National Institute of Diabetes and Digestive and Kidney Diseases (K23DK115906)
610-P: Effect of Butyrate on GI signs, SIBO, and Diabetes Control—Randomized, Placebo-Controlled Study in Patients with Type 2 Diabetes
Authors: PANUFNIK PAULINA , WIECEK MARTYNA , SZWARC PAULINA , KANIEWSKA MAGDALENA , LEWANDOWSKI KONRAD , FRANEK EDWARD , RYDZEWSKA GRAZYNA
Published: June 2024

Introduction & Objective: Patients with type 2 DM have frequently GI signs/symptoms and small intestinal bacterial overgrowth (SIBO), which may impair beta cell function and diabetes control. The study aimed to evaluate the influence of microencapsulated oral sodium butyrate on GI signs, SIBO incidence, and diabetes control.

Methods: In a prospective, randomized, placebo-controlled double-blind study, 52 patients with type 2 DM treated with diet or oral antidibetics (2 pts. on insulin) and abdominal pain were randomly assigned to butyrate 1.5 g/day (n=29) or placebo (n=23) for 12 weeks. Before and after the intervention the presence of abdominal pain, diarrhoea, constipation and flatulence was assessed, laboratory tests and hydrogen breath tests were performed, HbA1c was assessed.

Results: After the intervention in the butyrate group there was significantly more patients relieved from GI signs and symptoms as in the placebo group (Table 1). Additionally, there was a significant decrease of SIBO prevalence in the butyrate group as compared with placebo group. In the patients treated with butyrate a slight but significant improvement of BMI and HbA1C level was also observed (Table 1).

Conclusion: Oral microencapsulated sodium butyrate supplementation is effective in relieving abdominal signs, treating SIBO, improving body mass and metabolic control in patients with type 2 DM.

Disclosure

P. Panufnik: None. M. Wiecek: None. P. Szwarc: None. M. Kaniewska: None. K. Lewandowski: None. E. Franek: Speaker's Bureau; AstraZeneca. Research Support; BIOTON. Speaker's Bureau; BIOTON, Boehringer-Ingelheim, Berlin-Chemie AG, Merck & Co., Inc., Eli Lilly and Company, Novo Nordisk, Sanofi. G. Rydzewska: Speaker's Bureau; AlfaSigma. Consultant; AbbVie Inc. Speaker's Bureau; Bayer Inc., Pfizer Inc. Consultant; Takeda Pharmaceutical Company Limited. Speaker's Bureau; Janssen Pharmaceuticals, Inc.

Funding

The sodium butyrate preparation and placebo was provided by the Bioton company.
632-P: Beta-Cell Function Is a Stronger Predictor Than Insulin Resistance for Development of Type 2 Diabetes in Obese Indian Population—A Matched-Pair Cohort Analysis
Authors: TRIPATHI PRAMOD , KADAM NIDHI S. , VYAWAHARE ANAGHA R. , KATHRIKOLLY THEJAS , TIWARI DIPTIKA , SHARMA BABY , GANLA MALHAR H. , HIREMATH MAMATA , SABOO BANSHI D.
Published: June 2024

Background: Insulin resistance is often thought to be the primary factor in the development of type 2 diabetes, especially in obese individuals.

Aim: To determine the relationship between the homeostatic assessment model and diabetes, as well as the associated comorbidities, using matched-pair analysis in an obese Indian population.

Methods: The present study retrospectively analyzed data from 451 gender-age-BMI matched pairs (with and without diabetes) of obese patients (BMI > 25 kg/m², aged 40-60 years) enrolled in a one-year online lifestyle intervention program at the Freedom from Diabetes Clinic, India. Baseline anthropometric data, biochemical parameters, and medical history were used for the analysis. The homeostatic assessment model was used to calculate HOMA-IR and HOMA2-B. Insulin resistance was defined as HOMA-IR>2.5, while good beta cell function was defined as HOMA2-B >50.

Results: The mean age and BMI of the patients was 47.7±5.7 years and 31±4.5 kg/m², respectively; patients with diabetes had a mean disease duration of 7.9 years. Patients with diabetes had a significantly higher prevalence of insulin resistance (72.5%), inflammation (hs-CRP >3) (62%), hypertension (36%), and dyslipidemia (43%) than those without diabetes (37.5%, 47%, 27%, and 22%, respectively) (p<0.05). In contrast, good beta-cell function was observed in those without diabetes (96%) than those with diabetes (55.4%; 81% of them were on OHA) (p<0.05).

Conclusion: The majority of matched patients without diabetes exhibited good beta cell function. These findings emphasize that beta-cell function rather than insulin resistance may be the primary deficit leading to the development of diabetes in obese individuals.

Disclosure

P. Tripathi: None. N.S. Kadam: None. A.R. Vyawahare: None. T. Kathrikolly: None. D. Tiwari: None. B. Sharma: None. M.H. Ganla: None. M. Hiremath: None. B.D. Saboo: None.
640-P: Disordered Eating Screening within a Pediatric Diabetes Clinic
Authors: ANDORKO NICOLE , PANTESCO ELIZABETH J. , WILLI STEVEN M. , GENUARIO KIMBERLY , JENSSEN BRIAN , POWELL MAURA A. , DIFIORE GABRIELLE , GETTINGS JULIE M.
Published: June 2024

Adolescents with type 1 (T1D) and type 2 diabetes (T2D) are at elevated risk for mood and eating disorders, which are associated with numerous negative outcomes. Depression screening is now standard within pediatric diabetes clinics, yet formal screening for disordered eating is rare. Due to the comorbidity between these presentations, depression screening may effectively identify youth with disordered eating concerns. Goals were to describe the frequency of depressive and disordered eating symptoms for adolescents with T1D and T2D and examine associations between these symptoms. In a retrospective analysis of clinical data from outpatient medical visits in patients with T1D and T2D aged 13.0 to 18.9 years, body image and extreme weight control behaviors were assessed from a self-reported adolescent health questionnaire (AHQ; DiFiore et al., 2023) and depressive symptoms via the Patient Health Questionnaire-9 Adolescent Version (PHQ-9; Johnson et al., 2002). On average, patients with T1D (n = 216) were 15.9[1.25] years old, had diabetes for 7.7 [4.08] years, and an average BMI%ile of 75.95 [22.03]; while those with T2D (n = 85) were 16.1 [1.16] years old with diabetes for 2.7 [1.29] years, and an average BMI%ile of 98.05 [3.26]. Regarding depressive symptoms, 6.0% (T1D) and 11.8% (T2D) scored at or above threshold (≥ 11) on the PHQ-9. Concerns of body image were reported in 13.0% (T1D) and 42.4% (T2D) and of extreme weight control behaviors in 6.0% (T1D) and 27.1% (T2D). Linear regressions adjusted for relevant background variables including BMI indicated higher PHQ-9 scores were associated with both increased body image concerns (T1D: B = 4.14, p < .001; T2D: B = 3.41, p = .004) and extreme weight control behaviors (T1D: B = 3.49, p = .002; T2D: B = 4.30, p < .001). These findings highlight concern for disordered eating, especially within T2D, and routine screening is indicated. If clinic constraints limit multiple screenings, follow up disordered eating screening for those with concerning depressive symptoms may be appropriate.

Disclosure

N. Andorko: None. E.J. Pantesco: None. S.M. Willi: Advisory Panel; MannKind Corporation. Other Relationship; Medtronic. Advisory Panel; Boehringer-Ingelheim. Other Relationship; National Institute of Diabetes and Digestive and Kidney Diseases. K. Genuario: None. B. Jenssen: None. M.A. Powell: None. G. DiFiore: None. J.M. Gettings: None.
665-P: Inequities in Access to CGMs, Pump, and Insulin Pens among Type 1 Diabetes Adult Population at a Southeastern Academic Medical Center
Authors: HALL MEGAN , RODRIGUEZ CARLA , GONDER-FREDERICK LINDA
Published: June 2024

Introduction & Objective: Academic medical centers have identified disparities in access to diabetes technology. This analysis performed a self-assessment of potential inequities in access to diabetes technology at this medical center, including CGMs, insulin pumps, and insulin pens, to guide our community outreach efforts.

Methods: This study analyzed deidentified EMR data using multivariable logistic regressions to determine the association of social determinants (age, sex, race-ethnicity, insurance, and neighborhood socioeconomic disadvantage) with technology use among adults (ages≥18) with T1D.

Results: Of 1,480 patients with T1D seen at UVA Health in 2022, 479 accessed CGMs, 370 used pumps, and 133 used insulin pens. For CGMs, older age (80+ years), Non-Hispanic Black (NHB) race-ethnicity, public insurance and uninsured status related to lesser use/access. For pumps, female gender related to higher usage while NHB race-ethnicity and public insurance and uninsured status were associated with less use. Hispanic ethnicity was associated with higher pen use while Medicare/uninsured status related to with less use. (Fig 1.)

Conclusion: The majority of center patients do not use advanced technology for diabetes management, indicating that outreach efforts should target all racial-ethnic/SES groups with extra effort focusing on NHB groups and those with public/no insurance.

Disclosure

M. Hall: None. C. Rodriguez: None. L. Gonder-Frederick: None.

Funding

Lomar Foundation
678-P: Feasibility of Integrating Social Needs Interventions in Community-Based Diabetes Programs
Authors: VERDECIAS NIKO
Published: June 2024

Addressing diabetes disparities requires a holistic approach that recognizes the challenges faced by marginalized populations in integrating diabetes self-management education (DSME) into their daily lives. Unmet social needs such as food insecurity, unstable housing, and utility instability impact diabetes self-management behaviors and health outcomes. The purpose of this study is to understand the perspectives of community-based organizations (CBOs) that provide DSME to marginalized populations to identify social needs of their patients and approaches taken to address social needs. Semi-structured 1-on-1 interviews were conducted with (n=15) DSME facilitators and leadership from urban and rural CBOs. Using a Strengths, Weaknesses, Opportunities, and Threats (SWOT) framework, thematic analysis was performed to explore the feasibility of implementing a social needs intervention alongside DSME. Participants acknowledged the impact of social needs on their clients' self-management behaviors and highlighted the urgent need for intervention. Results revealed that the existing organizational structure and DSME programs provide flexibility for implementing a social needs intervention, but the CBOs expressed uncertainty about where to begin. Opportunities that could transform weaknesses into strengths included leveraging existing partnerships and establishing new ones to foster a greater sense of community within the CBOs to benefit their clients. Also, partnering with an expert to develop a concise standardized process and to train staff to screen and address social needs to strengthen CBO's rapport with their clients for personalized goal-setting. Needed is a focus on evaluating the effectiveness of integrating a social needs intervention into CBO services to improve DSM. This research aims to enhance the support provided to marginalized populations and address the multifaceted challenges they face in managing their diabetes.

Disclosure

N. Verdecias: None.
680-P: PAID-ing Off through Personalized Chronic Disease Management—Promising Preliminary Analysis in Alleviating Diabetes-Related Distress
Authors: BENOWITZ KYRA , WONG SHIRLEY , YOUNG CLIPPER F.
Published: June 2024

Objective: To examine whether a personalized chronic disease management approach induces a change in diabetes-related distress (DRD).

Methods: This pilot analysis - embedded in a clinical pharmacy program delivering care via telehealth and home visits, the Pharm2Home Initiative - utilizes a prospective design, comparing outcomes between two time points. DRD is measured using the Problem Areas in Diabetes 5-Item Scale (PAID-5). Inferential statistics were used to detect whether differences existed in each pair of PAID-5 item data and the total score.

Results: The primary and secondary outcomes are summarized below.

Conclusion: This preliminary analysis detected a significant difference in the total PAID-5 score with a 35% reduction from baseline, suggesting the personalized chronic disease management approach positively impacts participants’ DRD. Also, with no significant difference being detected in all measures within the secondary outcome, this intervention potentially induces a legacy effect where participants at least maintained a similar level of DRD three months after the intervention period. The outcomes thus far reflect an interprofessional effort, partnering clinical pharmacists with diabetologists and primary care providers to co-manage chronic diseases. Continuous monitoring is warranted to determine the program's impact on DRD.

Disclosure

K. Benowitz: None. S. Wong: None. C.F. Young: Other Relationship; Abbott.
712-P: Assessing the Relationship between Social Support, Depressive Symptoms, and Type 2 Diabetes Outcomes among Older Adults
Authors: SMALLS BRITTANY L. , TAYLOR ZOE M. , GONZABATO NELSON , SCHAEFER JILL
Published: June 2024

Type 2 diabetes (T2D) is an epidemic across the U.S. with a 11.6% prevalence for adults nationally, compared to 13.6 -23.6% spanning urban and rural areas in Kentucky. Additionally, older adults are disproportionately affected, where 1 in 4 have T2D. Kentucky also has high rates of depression, which literature has shown a bi-directional relationship with T2D. Therefore, this study sought to evaluate the relationship between social support, depressive symptoms, and T2D outcomes among older adults living in Kentucky.  Social support and depression were assessed using the MOS Social Support Survey and the Geriatric Depression Scale (GDS). Respondents were also asked to name up to 3 individuals in their support network. Mean raw MOS scores were enumerated and subscale means were converted to percentages. Spearman correlation was used to assess associations. There were 55 participants with a mean A1C of 7.02%. Of those, 49.09% reported three social support members, and only 7.27% reported zero social support. MOS revealed generally increasing scores highlighting a robust network size has direct impact on diabetes management. Social network size was negatively correlated with GDS scores (r= -0.13, p=0.38) and positively correlated with all MOS subscales. The overall MOS score was negatively correlated with A1c (r= -0.19, p=0.2) as was network size (r= -0.09, p=0.54). GDS scores showed a weak negative correlation with A1c (r= -0.10 p=0.52). Social support was associated with fewer depressive symptoms and improved glycemic control. Future longitudinal studies with larger and more diverse samples could further clarify these relationships.

Disclosure

B.L. Smalls: None. Z.M. Taylor: None. N. Gonzabato: None. J. Schaefer: None.

Funding

National Institutes of Diabetes and Digestion and Kidney Disease (5K01DK116923-05)
751-P: Benefits of HR17031, a Fixed-Ratio Combination of INS068 and SHR20004, vs. Its Components Alone in Patients (pts) with Type 2 Diabetes (T2D) Uncontrolled on Oral Antidiabetic Drug(s) (OADs)
Authors: JI LINONG , HUANG DEBING , LIN XIANG , DONG XUE , LI LU , SUN QINGYUAN , SUN XIAODONG , MAO LI , ZHAO SHI , WANG QUANREN , YE ZI
Published: June 2024

Introduction & Objective: HR17031 is a once-daily, novel combination of basal insulin analogue (INS068) and GLP-1 receptor agonist (SHR20004). This trial assessed efficacy and safety of HR17031 vs INS068 and SHR20004 in pts with T2D.

Methods: In this randomized phase 2 trial, 455 Chinese adults with T2D (HbA1c 7.5%-11.0%; previous metformin±another OAD) were randomized (2:2:1) to daily injections of HR17031 (n = 183), INS068 (n = 182) or SHR20004 (0.12 mg/d; n = 90). Primary outcome was HbA1c change at 26 weeks.

Results: After 26 weeks, greater reduction in HbA1c from baseline was achieved with HR17031 compared with INS068 and SHR20004 (-2.4% vs -1.5% and -1.7%; Fig 1), indicating superiority for HR17031 vs both INS068 (difference [D] = -0.9%) and SHR20004 (D = -0.7%). More pts reached HbA1c target <7% and <6.5% with HR17031 (<7%, 81.4%; <6.5%, 74.3%) than INS068 (47.8%; 26.4%) and SHR20004 (55.6%; 41.1%). HR17031 led to weight loss in contrast to INS068 (-0.1 vs 2.0 kg). Insulin dose of HR17031 was lower than INS068 (30.3 vs 38.1 U/d). All the above results were statistically significant (all P <0.001). Documented <3.0 mmol/L hypoglycemia was similar with HR17031 (5.5%) and INS068 (4.4%). No unexpected safety issues occurred.

Conclusion: HR17031 is effective and well-tolerated in pts with T2D uncontrolled on OAD(s).

Disclosure

L. Ji: None. D. Huang: None. X. Lin: Employee; Jiangsu Hengrui Pharmaceuticals Co., Ltd. X. Dong: Employee; Jiangsu Hengrui Pharmaceuticals Co., Ltd. L. Li: Employee; Jiangsu Hengrui Pharmaceuticals Co., Ltd. Q. Sun: None. X. Sun: None. L. Mao: None. S. Zhao: None. Q. Wang: Employee; Jiangsu Hengrui Pharmaceuticals Co., Ltd. Z. Ye: Employee; Jiangsu Hengrui Pharmaceuticals Co., Ltd.

Funding

Jiangsu Hengrui Pharmaceuticals Co., Ltd (sponsor)
766-P: Long-Term Effectiveness Associated with Maintenance Doses of Once-Weekly Semaglutide in U.S. Adults with Poorly Controlled Type 2 Diabetes
Authors: TAN XI , CAO YIWEN , DUNN TYLER J. , LIANG YUANJIE , NOONE JOSHUA , GAMBLE CORY L. , KING AARON A.
Published: June 2024

Introduction & Objective: To evaluate long-term effectiveness associated with maintenance doses of once-weekly semaglutide (sema) in US adults with poorly controlled type 2 diabetes (T2D).

Methods: Observational cohort study (Optum Clinformatics® Data Mart, Jan 2017-Dec 2022). Eligibility criteria: confirmed diagnosis of T2D, HbA1c ≥9.0% and newly initiated sema. Exclusion criteria: T1D and pregnancy. HbA1c outcomes were assessed in the 2nd year of follow-up in three groups reaching: 0.5 mg only; ≥0.5 mg; and 1 mg. Time to initiation (TTI) of new glucose‑lowering therapy (GLT) was assessed in patients (pts) reaching 1 mg within 1 year.

Results: Among 2311 pts, the 1 mg group (50.2%) had worse overall health and T2D at baseline vs the 0.5 mg-only group (32.5%). There was a ~2.5% reduction in HbA1c in the second year of follow‑up, across all groups (Table). After reaching 1 mg sema, 29.5% of pts newly initiated any GLT, 14.9% initiated SGLT-2i and 6.9% insulin. Average TTI of any new GLT was 208 days. TTI of insulin or SGLT-2i after dose escalation to 1 mg was 235 days and 234 days, respectively, and from sema initiation was 312 and 310 days, respectively.

Conclusion: In pts with poorly controlled T2D, sema maintenance doses were associated with a considerable reduction in HbA1c and delay in insulin initiation in a 2-year follow-up, highlighting the importance of a maintenance dose in such pts.

Disclosure

X. Tan: Employee; Novo Nordisk, Merck & Co., Inc. Y. Cao: None. T.J. Dunn: Employee; Novo Nordisk. Y. Liang: Employee; Novo Nordisk. J. Noone: Employee; Novo Nordisk. C.L. Gamble: Employee; Novo Nordisk. A.A. King: Speaker's Bureau; Abbott, MannKind Corporation, Novo Nordisk. Advisory Panel; Novo Nordisk. Speaker's Bureau; Lilly Diabetes. Advisory Panel; Lilly Diabetes. Speaker's Bureau; Dexcom, Inc. Advisory Panel; Dexcom, Inc. Speaker's Bureau; Astellas Pharma Inc.

Funding

Novo Nordisk Inc.
768-P: A Phase 1b/2a Trial to Assess the Safety, Tolerability, Pharmacokinetics, and Efficacy of PB-718, a GLP-1R/GCGR Dual Agonist in Subjects with Obesity
Authors:   STUDY GROUP PB-718, DING KE
Published: June 2024

Introduction: PB-718 is a fixed dose combination of PB-119 (GLP-1 receptor agonist) and PB-722 (glucagon receptor agonist in clinical development. Compared with a single molecule approach, PB-718 may offer the balance between GLP-1 and GCGR through adjusting the molar ratio of PB-119 and PB-722 to achieve optimal efficacy and safety. Linear pharmacokinetics, good tolerability and promising effect of weight loss have been demonstrated in a phase 1 study conducted in US. Here we report a phase 1b/2a study in Obesity

Methods: Thirty-six patients with obesity (BMI 30.5-40.0 kg/m2) without diabetes were randomized to this 3-sequential cohorts study (NCT06147544). In each cohort, 12 subjects were randomized (3:1) to receive PB-718 (PB-119/PB-722 600/1560 μg, 900/2340 μg or 1600/4160 μg) or placebo SC. injections once a week for 12-18 weeks. The primary endpoints were safety and PK profile. The secondary efficacy endpoints included changes in body weight (BW), BMI, lipids and HbA1c levels. Liver MRI-PDFF and body composition analysis were also assessed.

Results: Both PB-119 and PB-722 demonstrated dose-proportional increases in AUC0-last and Cmax ,showing linear, and synergic pharmacokinetics. At 12 weeks, BW, FPG, HbA1c, Lipid, insulin level and HOMA-IR all decreased dose-dependently, and significant reduction in BW of over 4-6% were observed. Serum uric acid was also decreased. Liver fat content and visceral fat mass also showed significant and dose-related reduction with PB-718 treatment. Meanwhile, PB-718 groups lost more fat mass than lean mass. GI side effects were the most common AEs, and were all grade 1 in severity.

Conclusions: PB-718 was safe, had predicted PK profile, and led to greater reductions in BW, HbA1c, blood lipids, uric acid, liver fat content and visceral fat mass. These data highlight the potential for PB-718 to provide additional benefit, and support the development of PB-718 as a promising treatment for obesity and NASH.

Disclosure

K. Ding: None.
776-P: Potent Weight Loss and Favorable Glycemic Control Effects of a Novel Long-Acting GLP-1/GIP/GCG Triple Agonist, HM15275, in Animal Models
Authors: HYUN PARK SANG , KIM YOHAN , KUK KIM JUNG , LEE DAHAE , PARK EUNJIN , KIM JEONG A. , HONG SUNGHEE , CHOI JAEHYUK , BAE SUNGMIN , HYUN LEE SANG , YOUNG CHOI IN
Published: June 2024

Introduction & Objective: The prevalence of obesity is increasing worldwide, urging development of obesity drugs with better efficacies and weight loss qualities. HM15275 is a GLP-1/GIP/Glucagon triple agonist designed to have well-harmonized activities and long-acting property for maximized body weight reduction. To elaborate the effects, a series of studies were conducted to evaluate (1) proper target engagement, (2) pharmacokinetics, and (3) body weight loss effects in DIO mice.

Method: Target receptor engagement of HM15275 was tested by cAMP assay with or without antagonist for each receptor. Plasma concentrations of HM15275 in rat and mouse were measured after a single subcutaneous dosing of HM15275. In DIO mice, body weight loss by HM15275 was compared with semaglutide and tirzepatide after 3 weeks treatment.

Results: Maximal in vitro activities of HM15275 significantly reduced in the presence of selective GLP-1, GIP, or Glucagon antagonist (hGLP-1R: 94.56% to 0.81%, hGIPR: 97.85% to 14.07%, hGlucagonR: 95.16% to 4.14%), indicating proper target engagement. In addition, protracted pharmacokinetic profiles were observed in rodent models, (half-life in mouse: 12 ~ 16 hr and rat: 17 ~ 19 hr). In DIO mice, HM15275 remarkably decreased body weight compared to semaglutide or tirzepatide at week 3 (-39.9%, -15.0%, and -25.3% vs. baseline). Furthermore, pair-fed study showed both food intake inhibition dependent and independent weight loss by HM15275. Energy balance evaluation revealed enhanced energy expenditure by HM15275. ipGTT results indicated favorable glycemic control of HM15275.

Conclusion: As a novel long-acting triple agonist, the molecular characteristics of HM15275 had been elucidated, demonstrating superior weight loss compared to currently available anti-obesity drugs. Therefore, HM15275 could be a valuable therapeutic option for weight control and human study is ongoing to assess clinical relevance of such findings.

Disclosure

S. Park: None. Y. Kim: None. J. Kim: None. D. Lee: None. E. Park: None. J.A. Kim: None. S. Hong: None. J. Choi: None. S. Bae: None. S. Lee: None. I. Choi: None.
785-P: Preclinical Safety, Pharmacokinetics (PK), and Pharmacodynamics (PD) Assessments of Sustained-Released Formulation of Once-Monthly Injectable Semaglutide (PT403)
Authors: LEE JIHYANG , CHO JAEPYOUNG , JANG EUNSEO , KIM MIRI , BAE JIHYUN , CHOI MYUNG-JOO , CHANG SEUNG-GU , G JUNG JIN
Published: June 2024

Objective: Advancements in GLP-1RA research, shifting from daily to weekly injectables, have improved therapeutic outcomes and expanded market potential, paving the way for monthly injectable drug development. This study evaluates the clinical potential of PLGA-encapsulated once-monthly injectable semaglutide through extensive non-clinical assessments, including safety profiling and pharmacokinetic/pharmacodynamic evaluations.

Methods: Semaglutide was solubilized in acetic acid with a diverse biodegradable PLGA polymer mixture and processed using ultrasonic spray-drying to create microspheres encapsulating semaglutide. The optimized formulation, PT403, with a proper drug loading and no initial burst was developed. Subsequent assessments, including PK, PD, and toxicology, were conducted in mouse, rat, and/or minipig.

Results: PT403 exhibits favorable physicochemical properties, including uniform microsphere size (20μm), one-year stability, and extended release up to 70 days in minipigs. In a Single Ascending Dose (SAD) study in mice, PT403 induced a 20% body weight reduction at doses ranging from 24 to 192 mg/kg. No other notable critical signs were observed, ensuring a safe profile even up to 192 mg/kg. Moreover, simulated release profiles suggest PT403's potential as a once-a-month injectable, with a Peak-to-Trough ratio of 1.4. Both semaglutide and PT403 demonstrated consistent reductions in body weight (30%) and cumulative food intake across 28 repeated injections of semaglutide and double injections of PT403.

Conclusion: PT403, featuring uniform microsphere size and favorable drug loading, exhibited safety in mice at the highest dose. Simulations support this formulation, and consistent pharmacodynamic effects across semaglutide and PT403 groups in repeated injections suggest its promise for clinical development as a monthly injectable for diabetes and obesity.

Disclosure

J. Lee: None. J. Cho: None. E. Jang: None. M. Kim: None. J. Bae: None. M. Choi: None. S. Chang: None. J. Jung: None.
800-P: Post Hoc Analysis of Phase III Study of Liraglutide Biosimilar with Reference Biologic in Obese Type 2 Diabetes Mellitus Indians
Authors: JOSHI SHASHANK R. , BARKATE HANMANT V. , MANE ABHISHEK , PETARE ANUP U. , CHOUDHARI SANJAY Y.
Published: June 2024

Background: Biosimilar of Liraglutide developed in India has demonstrated non-inferiority in terms of safety, efficacy and quality compared to reference biologic. Basis this biosimilar of Liraglutide has been approved in India for management of T2DM. Data generated in Indian obese T2DM was further analyzed to see efficacy & safety with biosimilar of Liraglutide

Methods: This post hoc analysis assessed the efficacy & safety of Liraglutide biosimilar & reference biologic in obese T2DM Indians. Aim of this analysis was to assess mean change in glycemic parameters from baseline to week 24 in both the groups.

Results: Total 179 Obese patients (BMI 25 kg/m2 and above) were included in the post-hoc analysis. As shown in table 1 the change in HbA1c, FPG & PPBG at week 24 was significant compared to baseline in obese patients with biosimilar of Liraglutide & reference biologic (p<0.001). However, there was no significance between the change in glycemic parameters when intergroup comparison done for biosimilar of Liraglutide & reference biologic treatment.

Conclusion: Biosimilar of Liraglutide demonstrated comparable glycemic control with respect to the reference biologic in terms of reduction in HbA1c, FPG and PPBG from baseline to Week 24 in obese T2DM patients.

Disclosure

S.R. Joshi: Consultant; Twin Health, Marico, Franco Indian, Zydus Cadila, Glenmark Pharmaceuticals. Other Relationship; Novo Nordisk, Sanofi, MSD, Abbott Nutrition, Abbott, Biocon, Alkem, USV Private Limited, Boehringer-Ingelheim. H.V. Barkate: Employee; Glenmark Pharmaceuticals. A. Mane: None. A.U. Petare: Employee; Glenmark Pharmaceuticals. S.Y. Choudhari: Employee; Glenmark Pharmaceuticals, Sun Pharmaceutical Industries Ltd.

Funding

Glenmark Pharmaceuticals Ltd.
804-P: Understanding Off-Label Use of GLP-1 (Glucagon-Like Peptide-1 Receptor) Agonists among Providers Participating in the T1D Exchange Quality Improvement Collaborative (T1DX-QI)
Authors: PAT GALLAGHER MARY , BASINA MARINA , OSPELT EMMA L. , RIOLES NICOLE , BREIDBART EMILY , ZUPA MARGARET , ENG DONNA , NG JASON , LEVY CAROL J. , EBEKOZIEN OSAGIE , COLLABORATIVE T1DX-QI
Published: June 2024

Background: The use of glucagon-like peptide-1 agonists (GLP-1a) as adjunctive therapy to insulin is not yet standard for people with type 1 diabetes (PwT1D) but is being explored.

Methods: T1DX-QI Collaborative administered a Qualtrics survey to providers at 55 centers Jul.-Sept. 2023 to determine current opinions and practices regarding the use of GLP-1a in PwT1D. Descriptive analysis was performed.

Results: Fifty of 55 centers (91%) completed the survey. Fifty percent of pediatric and 75% of adult centers reported that GLP-1a have a role in T1D management as an adjunctive therapy to insulin. Both pediatric and adult centers reported that they would consider adding a GLP-1a to insulin therapy in PwT1D, based on BMI and total daily insulin dose. Adult providers were more likely to consider the PwT1D’s desire to lose weight, personal or family history of early ASCVD, and presence of NAFLD compared with pediatric providers (Fig. 1). Both adult and pediatric centers reported insurance coverage as a barrier even when PwT1D meet criteria for GLP-1a treatment for weight loss based on BMI.

Conclusions: A large percentage of centers report that GLP-1a have a role in T1D management. Providers consider a range of factors when adding GLP-1a to insulin therapy in PwT1D, including data that BMI is an independent risk factor for early ASCVD in PwT1D.

Disclosure

M. Gallagher: None. M. Basina: None. E.L. Ospelt: None. N. Rioles: None. E. Breidbart: None. M. Zupa: None. D. Eng: None. J. Ng: Research Support; Sanofi-Aventis U.S., T1D Exchange. C.J. Levy: Research Support; Dexcom, Inc. Consultant; Dexcom, Inc. Research Support; MannKind Corporation, T1D Exchange, Tandem Diabetes Care, Inc., Abbott, Insulet Corporation. O. Ebekozien: Advisory Panel; Sanofi, Medtronic. Research Support; Vertex Pharmaceuticals Incorporated. Speaker's Bureau; Vertex Pharmaceuticals Incorporated. Research Support; Medtronic, Lilly Diabetes, Abbott, Dexcom, Inc.

Funding

The Leona M. and Harry B. Helmsley Charitable Trust
805-P: Development of a Semaglutide-Releasing Long-Acting Injectable, IVL3021, and Its Physicochemical and Pharmacokinetic Studies
Authors: KIM MINSUNG , LEE SLGIRIM , HEE KIM JU
Published: June 2024

For many chronic conditions, microsphere-based long-acting injectables (LAIs) have been employed to replace repetitive daily or weekly therapies with long-term therapies (e.g. 1 month). The key technology to develop LAIs is controlling release profiles since it is significant not only to patient adherence and efficacy but also to the safety of the medications by minimizing the burst exposure of the drug and keeping its drug level within the therapeutic range. The focus of the current study is on semaglutide (Sema), an FDA-approved glucagon-like peptide-1 (GLP-1) receptor agonist for managing diabetes and obesity. Most annoying adverse events that Sema induces are gastrointestinal AEs, which can be mitigated by using LAIs. However, encapsulating it into microparticles and controlling the release have presented challenges, given its physicochemical properties. In this study, we introduce a novel one-month LAI of Sema, named IVL3021, developed using IVL-DrugFluidics® technology. This microfluidics-based manufacturing approach enables precise control of drug release through size and morphology-regulated microspheres. Our study demonstrates the smooth uniform spherical morphology of IVL3021 microspheres, with an encapsulation efficiency exceeding 97.0%. Importantly, in preclinical pharmacokinetic studies, IVL3021 maintains plasma concentrations of Sema within the therapeutic range over 4 weeks without an initial burst release.

In conclusion, IVL3021 showed its potential to be used as a 1-month LAI of Sema for obesity and diabetes management. The current study also suggested the potential of IVL-DrugFluidics® Technology in creating size-controlled peptide-encapsulating microspheres. Based on the positive results, further preclinical evaluation is ongoing.

Disclosure

M. Kim: Employee; Inventage Lab Inc. S. Lee: Employee; Inventage Lab Inc. J. Kim: Board Member; Inventage Lab Inc.
814-P: What Are the Early Selection Predictors of GLP-1 Receptor Agonists in Real-World Data for Japanese Individuals with Type 2 Diabetes?
Authors: SUGANUMA YUKA , ISHIGURO MIZUKI , OHNO TAKAYUKI , NISHIMURA RIMEI
Published: June 2024

Introduction & Objective: The objective of this study is to elucidate the prescription order of GLP-1 receptor agonists (GLP-1RA) and predictors affecting their selection in Japanese type 2 diabetes (T2D) using real-world data.

Methods: The subjects were extracted from individuals with T2D attending our 4 hospitals (approximately 10,000/month in outpatient attendance) newly prescribed GLP-1RA between 2016 and 2019, excluding those initiated during hospitalization. Using clinical information databases, we examined patient backgrounds and changes over time in selection orders of GLP-1RA among antidiabetic drugs, as well as concurrent drugs. To identify predictors for GLP-1RA being the first or second choice, multiple regression analysis was performed with variables such as age, gender, prescription year, medical history, BMI, HbA1c, presence of chronic kidney disease (CKD), and insulin use as independent variables.

Results: We included 671 participants (259 females) with a median age [25-75 percentile] of 61.0 [50.0-72.0] years and BMI of 27.3 [23.8-31.6] kg/m2. Among GLP-1RA, 62.6% were dulaglutide, while 36.1% were liraglutide. GLP-1RA remained third new prescription from 2016 to 2019, with no changes over time. Switching from other medications accounted for 76.5% (1st: DPP4i, 2nd: rapid-acting insulin), while adding to current treatments constituted 23.5%. When prescribed as the third choice, the most common pre-prescribed combination was biguanide + insulin throughout the study period. The predictors for the early selection of GLP-1RA were older age, given the popularity of low-dose dulaglutide, and presence of CKD.

Conclusion: GLP-1RA was the third choice among antidiabetic drugs, with frequent switches from DPP4i or insulin. It was considered that older age or the presence of CKD were predictors for early selection of GLP-1RA. We will monitor for changes in predictors with introduction of semaglutide and tirzepatide.

Disclosure

Y. Suganuma: None. M. Ishiguro: None. T. Ohno: None. R. Nishimura: Speaker's Bureau; Abbott. Advisory Panel; Abbott Japan Co., Ltd. Speaker's Bureau; Boehringer-Ingelheim, Mitsubishi Tanabe Pharma Corporation, Kowa Company, Ltd., Medtronic, Sanofi, Taiho Pharmaceutical Co. Ltd., Sumitomo Dainippon Pharma Co., Ltd., Teijin Pharma Limited, Eli Lilly and Company, Novo Nordisk A/S. Consultant; Terumo Corporation.
816-P: Health Care Resource Utilization and Costs with Timely vs. Delayed Basal Insulin Initiation
Authors: BILLINGS LIANA K. , SHETH SUNNY T. , BRADY BRENNA , RICHARDS MEGAN , RAJPURA JIGAR R. , MITRI JOANNA
Published: June 2024

Introduction & Objective: Many patients with uncontrolled type 2 diabetes (uT2D) on other glucose-lowering medications (GLMs) eventually require basal insulin, but initiation is often delayed. This study assessed the potential impact of the timing of insulin initiation by examining healthcare utilization and costs among patients with timely vs delayed basal insulin initiation.

Methods: In the 2011-2018 MerativeTM Claims-EHR Database, adults with uT2D who were candidates for basal insulin (HbA1c>7%, ≥2 GLMs totaling ≥180 days’ supply, no new GLM class in the next 90 days) and newly initiated treatment were selected. The index date was the first basal insulin fill. Timely and delayed initiators started treatment <6 months and ≥6 months after meeting criteria for uT2D, respectively. Patients had ≥12 months of pre- and post-enrollment, no claims for type 1 diabetes or pregnancy, and ≥1 claim for T2D. All-cause healthcare utilization and costs were compared between cohorts in the pre- and post-periods.

Results: This study included 1,054 (29.2%) timely and 2,561 (70.8%) delayed initiators. Prior to basal insulin initiation, timely initiators had greater use of inpatient and emergency services, and significantly higher total costs ($26,460±$60,743 vs $21,703±38,825, p<0.01) and mean HbA1c (9.3±1.8 vs 8.9±1.5, p<0.001) compared to delayed initiators. Following treatment, both cohorts had similar utilization, costs and HbA1c values. Total costs from the pre- to post-period decreased in the timely initiator cohort (-$827) despite higher initial costs but increased in the delayed initiator cohort ($4,788).

Conclusion: Given the chronic nature of T2D, decreases in total costs over the study period among timely initiators highlighted the potential benefits of prompt basal insulin initiation for containment of healthcare costs. The same economic benefits were not observed among delayed initiators whose costs increased 22% in the post-period.

Disclosure

L.K. Billings: Advisory Panel; Novo Nordisk, Pfizer Inc. S.T. Sheth: Employee; Novo Nordisk. B. Brady: None. M. Richards: None. J.R. Rajpura: Employee; Novo Nordisk. J. Mitri: Advisory Panel; MannKind Corporation. Consultant; Novo Nordisk. Research Support; Kowa Pharmaceuticals America, Inc. Consultant; Lilly Diabetes, Dianomi-. Employee; sequelmedtech. Consultant; AbbVie Inc., beigene-spouse, cellectar-spouse, kite-spouse, Janssen Pharmaceuticals, Inc., loxo- spouse, AstraZeneca.

Funding

Novo Nordisk Inc.
82-OR: Association of Diabetic Complications and Various Comorbidities with Major Adverse Cardiovascular Events in Type 2 Diabetes and Their Development over Time—A Danish Registry-Based Case-Control Study
Authors: BECH ASGER A. , MADSEN MIA D. , KVIST ANNIKA V. , VESTERGAARD PETER , RASMUSSEN NICKLAS H.
Published: June 2024

Introduction and Objective: Type 2 diabetes mellitus (T2DM) is associated with an increased risk of cardiovascular disease (CVD). This study aimed to investigate the association between risk factors for major adverse cardiovascular events (MACE) over time.

Methods: In this case-control study, data from Danish registries was utilized to identify peopled diagnosed with T2DM between 1999-2018 (n=347,121) and then subdivided into cases and controls for each of two 10-year time periods; TP1: 1999-2008 and TP2: 2009-2018. Cases were defined as having suffered three-point MACE (nTP1=13,584, nTP2=10,823) with controls matched 1:1 on age, gender, and T2DM duration. Exposures were preselected diabetic complications and comorbidities, identified using ICD-10 and/or ATC codes. The association was analyzed using conditional logistic regression.

Results: Comorbidities strongly associated with MACE included hypertension (ORTP1 = 2.32, 95% CI 2.18-2.47 ORTP2 = 1.92, 95% CI 1.81-2.04), hypercholesterolemia (ORTP1 = 1.73, 95% CI 1.60-1.86, ORTP2 = 1.25, 95% CI 1.17-1.32), diabetic complications; nephropathy (ORTP1 = 1.77, 95% CI 1.48-2.11, ORTP2 = 1.74, 95% CI 1.41-2.15), neuropathy (ORTP1 = 2.27, 95% CI 2.06-2.49 ORTP2 = 1.95, 95% CI 1.78-2.13) and retinopathy (ORTP1 = 1.18, 95% CI 1.05-1.34, ORTP2 = 1.51, 95% CI 1.28-1.78). Hypercholesterolemia and hypertension showed a significant decrease between the periods. Additionally, osteoarthritis (ORTP1 = 0.83, 95% CI 0.75-0.92 ORTP2 = 0.81, 95% CI 0.74-0.88) exhibited a significant inverse association with MACE.

Conclusion: These results suggested that certain risk factors improved over time. However, there is still a need for further improvement in the prevention of MACE in T2DM.

Disclosure

A.A. Bech: None. M.D. Madsen: None. A.V. Kvist: None. P. Vestergaard: None. N.H. Rasmussen: Other Relationship; Boehringer-Ingelheim. Stock/Shareholder; Novo Nordisk, Eli Lilly and Company.

Funding

This work was supported by a research grant from the Danish Diabetes and Endocrine Academy, which is funded by the Novo Nordisk Foundation (NNF22SA0079901)
831-P: Preferences of People with Type 1 Diabetes for Features of Weekly Insulin
Authors: SCHAPIRO DAVID , PEREZ-NIEVES MAGALY , VASS CAROLINE M. , LING POON JIAT , GELSEY FELICIA , PIERCE ANNA , MANSFIELD CAROL
Published: June 2024

Introduction & Objective: Once-weekly insulin has the potential to increase willingness to initiate and adhere to insulin therapies in people with type 2 diabetes requiring basal-only insulin therapy. However, the role of once-weekly insulin in people already treated with basal-bolus multiple daily injection regimens, such as people with type 1 diabetes (PwT1D), is less understood. This study aimed to quantify the preferences of PwT1D for novel long-acting insulins.

Methods: A discrete choice experiment survey was administered to PwT1D in the United States. The survey included 8 questions offering a choice between experimentally designed pairs of hypothetical, long-acting insulins that varied by 6 attributes: reduction in A1c level after 6 months, daily time in range (TIR), number of serious low blood sugar events, number of nighttime low blood sugar events, weight change over 6 months, and administration frequency. A fixed choice question directly elicited preferences for flexible weekly over daily insulin, holding all other attributes equal. Data were analyzed with random-parameter logits.

Results: The survey was completed by 200 PwT1D (mean: age = 41 years; A1c = 7.6%; 57% female). They were on a basal (100%), mealtime bolus (98%), or intermediate or premixed insulin (2%). Across attributes, respondents ranked achieving the longest TIR as the most important change, followed by equal importance on the largest change in the number of serious low blood sugar events per month, avoiding a 10 pound weight change, the largest change in the number of nighttime low blood sugar events per month, and weekly over daily basal administration. The largest reduction in HbA1c was the least important attribute in respondents’ decisions. In the fixed-choice question, 73% of people preferred flexible weekly over daily dosing for basal insulin.

Conclusion: The most important attributes were changes in TIR and number of serious hypoglycemic events. PwT1D preferred weekly over daily basal insulin when all other attributes were equal.

Disclosure

D. Schapiro: Employee; Eli Lilly and Company. M. Perez-Nieves: Employee; Eli Lilly and Company. Stock/Shareholder; Eli Lilly and Company. C.M. Vass: Other Relationship; Eli Lilly and Company. Consultant; National Institute for Health and Care Excellence (NICE). J. Poon: Employee; Eli Lilly and Company. Stock/Shareholder; Eli Lilly and Company. F. Gelsey: Employee; Eli Lilly and Company. Stock/Shareholder; Eli Lilly and Company. A. Pierce: None. C. Mansfield: None.
84-OR: Performance of FIB-4 Score in Predicting Mortality among Patients with Nonalcoholic
Authors: PAIK JAMES M. , GOLABI PEGAH , JOÃO MENESES MARIA , MACEDO PAULA , HENRY LINDA , YOUNOSSI ZOBAIR
Published: June 2024

Introduction & Objective: T2D in NAFLD is associated with adverse outcomes. FIB-4 score identifies high-risk NAFLD. The association of FIB-4 with mortality among NAFLD with T2D was assessed.

Methods: NHANES III-linked mortality data were used. NAFLD is defined by ultrasound without other causes of liver disease. Low risk FIB-4: <1.30 age <65/2.0 age≥65; high-risk FIB-4 ≥ 2.67.

Results: There were 738 patients with NAFLD and T2D (mean age, 58.6 [11.0] years; 41.3% male; 55.8% obesity). Compared to non-obese NAFLD+T2D, obese NAFLD+T2D were younger (57.5 vs. 60.0 years), female (64.1% vs. 51.8%) with higher hyperlipidemia rates (91.3% vs. 84.4%). No difference in 10-year cumulative mortality by obesity (obese 21.1% vs. non-obese 26.7%, p=0.077). Proportion of low, intermediate, and high-risk groups (obese 79.0%, 17.5%, 3.5% vs. non-obese 82.2%, 14.0%, 3.7%, p-values>0.20). FIB-4 area under the ROC for 10-year mortality was 0.68 [0.62-0.73]) for non-obese NAFLD+T2D and 0.61 [0.56-0.66] for obese NAFLD+T2D. Compared to non-obese NAFLD+T2D, FIB-4 had lower predictive ability for mortality for obese NAFLD+T2D. Per Youden index, lower FIB-4 threshold of 0.92 provided better 10-year mortality risk in both obese and nonobese NAFLD+T2D.

Conclusion: Presence of obesity among NAFLD+T2D negatively impacts FIB-4 performance. Lower FIB-4 threshold improves the predictive value of FIB-4 in both obese and non-obese NAFLD+T2D.

Disclosure

J.M. Paik: None. P. Golabi: None. M. Meneses: None. P. Macedo: None. L. Henry: None. Z. Younossi: Consultant; Gilead Sciences, Inc., Bainan Biotech, AbbVie Inc., Bristol-Myers Squibb Company, Abbott, Novo Nordisk, Madrigal Pharmaceuticals, Inc., Merck & Co., Inc., Siemens Healthcare Diagnostics, Intercept Pharmaceuticals, Inc.