Citations

Abstract Disclosure: E.M. Lewiecki: Amgen Inc, Radius Health, Inc. K. Tough DeSapri: Amgen Inc, Radius Health, Inc. S. Denning: Amgen Inc, Radius Health, Inc. S.T. Harris: Amgen Inc, Radius Health, Inc. J.G. Sfeir: None. Y. Wang: Radius Health, Inc. J.A. Chiodo: Radius Health, Inc. F. Cosman: Amgen Inc, Biocon, Curateq, Enterabio, Radius Health, Inc, Theramex, UCB. Objectives: Studies have shown that the sequence of osteoporosis (OP) treatment can affect clinical outcome measures and likelihood of attaining therapeutic targets. The aim of this descriptive study was to evaluate the long-term OP treatment patterns in US patients prescribed anabolic therapies (ie, abaloparatide [ABL], teriparatide [TPTD], romosozumab [ROMO]). Methods: Anonymized patient claims data from a subset of ICON’s Symphony Health Patient Source Integrated Dataverse database was utilized. Men and women, aged ≥50 years with at least one prescription claim for ABL, TPTD, or ROMO from May 1, 2019 to April 30, 2021 were included. The index date was the date of the first anabolic treatment claim. For study inclusion, patients were required to have medical and pharmacy record information from 5 years prior to the start of, and 1 year after discontinuation of, anabolic treatment. Patients with a history of anabolic therapy in the 5 years prior to the index date were excluded. Results: 42,400 patients (ABL, n=16,673; TPTD, n=19,575; ROMO, n=6152) were included, of which 80%–90% were women. Persistence rates were low for all anabolic therapies. Overall mean (standard deviation [SD]) duration was 6.5 (5.8), 6.2 (5.6), and 6.0 (4.5) months for the ABL, TPTD, and ROMO groups, respectively, with approximately 45% of patients in the ABL and TPTD groups and 40% of patients in the ROMO group receiving therapy for ≤3 months. Only 18% (ABL) and 17% (TPTD) of patients received over 12 months of anabolic treatment, and 27% of patients in the ROMO group received over 9 months of treatment. In the 5 years prior to anabolic therapy, 35% (ABL), 34% (TPTD), and 47% (ROMO) of patients had prior OP treatment, with the majority having received an oral bisphosphonate (ABL, 26%; TPTD, 25%; ROMO, 21%) for a mean (SD) treatment duration of 15.8 (13.7), 15.5 (13.3), and 16.6 (14.4) months, respectively. The second most prescribed prior therapy was denosumab (ABL, 7%; TPTD, 7%; ROMO, 24%). In the 12 months after anabolic therapy, only 21% of patients in the ABL and TPTD groups received subsequent OP medication, the majority with either denosumab (9%) or oral BP (9%), and 49% of patients treated with ROMO received subsequent treatment, most of which was with denosumab (36%). Conclusions: The pattern of prescriptions of anabolic therapy in US adults identifies significant gaps in the treatment of skeletal fragility. Despite current clinical practice guidelines, the mean duration of anabolic treatment was less than 7 months, and a large majority of patients did not receive subsequent OP prescription following anabolic therapy. Additional research is needed to understand and overcome the obstacles in applying standard of care practices. Further analyses will reveal the clinical outcomes of these treatment patterns. Presentation: Saturday, July 12, 2025

Abstract Disclosure: K. Yu: None. J. Saini: None. E.J. Atkinson: None. S.J. Achenbach: None. V. Fell: None. I. Bancos: None. Background: Data on cognition in patients with primary aldosteronism (PA) are scarce. Mild autonomous cortisol secretion (MACS), defined based on post-dexamethasone cortisol >1.8 mcg/dL, is diagnosed in 20-30% of patients with PA. The impact of MACS on the cognition of patients with PA is unclear. Objectives: 1) to assess cognition in patients with PA versus sex-matched referent subjects with hypertension, 2) determine the differences in cognition of patients with PA (with and without MACS) and patients with MACS. Methods: A cross-sectional study, 2019-2023. Cognition was assessed by National Institute of Health Toolbox Cognition Battery and reported as T-score corrected for age, sex, race, and education. Only subjects with hypertension were included. Results: Cognitive assessment was performed in 52 patients with PA (including 11 patients with both PA and MACS, median age of 51 yrs, 30, 58% women), 47 patients with MACS (median age of 57 yrs, 31, 66% women), and 52 referent subjects (median age of 66 yrs, 30, 58% women). When compared to referents, and after age adjustment, patients with PA had lower cognition: fluid composite cognition β of -6.3 (P=0.014) and total composite of -5.6 (P=0.016). When compared to patients with MACS, and after age and sex adjustment, patients with PA had a similar total composite cognition score (β=3.6, P=0.108) but a higher fluid composite score (β=4.7, P=0.044). No differences in cognition were found between patients with PA with and without MACS, possibly due to low sample size. Conclusion: Patients with PA demonstrate lower cognition when compared to referents with hypertension. Patients with PA had a higher fluid cognition compared to patients with MACS. Future studies should delineate the impact of hyperaldosteronism vs MACS on cognition of patients with PA. Presentation: Monday, July 14, 2025

Abstract Disclosure: H. Ahmad: None. M. Kakakhel: None. A. Ullah: None. M. Saeed: None. J. Ikram: None. A. Qadeer: None. M. Khawar: None. H. Jawad: None. S. Haider: None. R. Haider: None. F. Ahmed: None. R.W. Kirchoff: None. Background: Type 1 diabetes mellitus (T1DM) is an autoimmune disease characterized by the destruction of insulin-producing cells in the pancreas. It is a global health concern with regional variation in incidence and prevalence. This study aims to analyze the regional incidence and prevalence of T1DM among adolescents and young adults (15-39 years) from 1990 to 2021 in 26 regions. Methods: Global Burden of Disease (GBD) data for 2021 were analyzed to assess regional incidence and prevalence of T1DM among adolescents and young adults. The Annual Average Percentage Change (AAPC) was calculated to evaluate trends from 1990 to 2021, with statistical significance determined using p-values. Results: In 2021, middle socio-demographic index (SDI) has the highest incidence (54541) as well as prevalence (1.86 million), followed by Low-middle SDI (I: 48416, P: 1.80 million) and South Asia (I: 46310, P: 1.73 million). Oceania has the lowest incidence (356) as well as prevalence (12885), followed by Andean Latin America (I: 911, P: 31954) and Caribbean regions (I: 1214, P: 54610), respectively. The largest increase in AAPC of incidence was showed by Southern Latin America (2.23, CI: 2.11-2.30), High-income Asia Pacific (2.22, CI: 2.18-2.26), and Western Europe (1.80, CI: 1.73-1.84) regions, while Western Europe (1.72, CI: 1.66-1.75), Eastern Europe (1.64, CI: 1.63-1.66), and Australasia (1.38, CI: 1.36-1.40) showed largest increase in AAPC of prevalence. The Caribbean region had the greatest decline in AAPC of prevalence (-0.11, CI: -0.08 to -0.12) followed by Eastern Sub-Saharan Africa (-0.07, CI: -0.06 to -0.09) and Central Latin America (-0.04, CI: -0.02 to -0.07). There was no region with decline in incidence. All AAPC values were statistically significant (p < 0.000001). Conclusion: Middle SDI region exhibited the highest incidence and prevalence, highlighting the vulnerability of these populations, while Oceania and Andean Latin America bore the least burden. Notably, several regions, particularly in Europe, experienced substantial increases in both incidence and prevalence, emphasizing the need for targeted interventions. Conversely, some regions, such as the Caribbean, showed encouraging declines in prevalence, suggesting that effective prevention and control strategies can be implemented. These findings underscore the importance of tailored approaches to address the evolving burden of T1DM. Presentation: Saturday, July 12, 2025

Abstract Disclosure: M. Kakakhel: None. S. Cheema: None. R. Haider: None. R. Noor: None. S. N.l: None. S.M. Irshad: None. A. Ullah: None. H. Jawad: None. A. Nawaz: None. M. Khawar: None. A. Qadeer: None. H. Ahmad: None. R. Alcaraz: None. F. Ahmed: None. Background: Bone density and structure-related disorders, such as osteoporosis and related fractures, significantly contribute to morbidity and mortality, particularly among aging populations. Monitoring temporal trends and geographic variations in mortality is essential to inform targeted public health interventions. In this study, we aimed to examine temporal and geographic variations in mortality associated with bone density and structure-related disorders in the United States from 1999 to 2022. Methods: Using ICD-10 codes M80-M85, this retrospective ecological study utilized mortality data extracted from the CDC WONDER database for the years 1999-2022. Age-adjusted mortality rates (AAMRs) were calculated and stratified by demographic variables (age, sex, and race/ethnicity) and geographic regions. Temporal trends were analyzed using Joinpoint regression to estimate annual percent changes (APCs). Geographic variations were visualized using choropleth maps, and subgroup analyses were performed to explore disparities. Statistical significance was set at p < 0.05. Results: Age-adjusted mortality rates (AAMRs) for bone density and structure-related disorders decreased overall from 1999 to 2019, with a subsequent rise observed in 2020 and 2022. Joinpoint regression revealed a significant negative trend from 2007-2016 (APC = -7.46%, p < 0.000001), followed by a positive reversal from 2019-2022 (APC = 3.78%, p = 0.013). Both males and females experienced declines in mortality, but females had a slightly higher APC of -3.10% compared to -2.82% for males. Asian/Pacific Islander groups exhibited the most pronounced decrease in mortality (APC = -11.92%, p < 0.000001) from 2009-2015, with a positive rebound in recent years. Black or African American populations had the smallest decline (APC = -1.35%). The Southern U.S. experienced the steepest decline in mortality from 2010-2016 (APC = -10.92%, p < 0.000001), followed by a strong positive trend from 2019-2022 (APC = 6.61%, p < 0.000001). Conversely, the West and Northeast regions showed milder trends with less pronounced reversals. Older age groups (65-74, 75-84) showed significant decreases in mortality, particularly the 65-74 group, which reversed to a positive trend (APC = 6.97%) from 2019-2022. The highest number of deaths occurred at the decedent’s home (3,330 in 2022). Subgroup analyses indicated significant temporal shifts in the mortality patterns across different racial/ethnic groups and geographic regions. Hispanic/Latino and Asian/Pacific Islander populations exhibited an increase in mortality rates post-2019, particularly in 2020. Conclusion: From 1999 to 2022, mortality from bone density and structure-related disorders in the U.S. exhibited significant temporal and geographic variations. These findings highlight the need for targeted public health strategies. Presentation: Monday, July 14, 2025

Abstract Disclosure: A. Ullah: None. R. Haider: None. M. Khawar: None. M. Abid: None. M. Hadeed Khawar: None. M. Shaukat: None. M. Asad Cheema: None. A. Komel: None. M. Ahmed Khan: None. R. Noureen: None. A. Batool: None. M. Mubashir: None. A. Qadeer: None. R. W. Kirchoff: None. Background: The role of dissecting the right paraesophageal lymph node (RPELN) in managing papillary thyroid carcinoma (PTC) remains a subject of debate. This meta-analysis examines both established and novel risk factors associated with RPELN metastasis. Methods: Relevant studies published up to December 2024 were retrieved using PubMed, Embase, Ovid, and Scopus search engines. Data were extracted and evaluated using the Newcastle-Ottawa scale. Statistical analysis was performed using Review Manager 5.4, with heterogeneity assessed through the Q-test and I²-test. Sensitivity analysis was conducted using the leave-one-out method, and the Egger regression test was used to generate a funnel plot for publication bias assessment. Results: Out of 2,444 articles screened, 26 studies involving 16,427 patients were included in the meta-analysis. The overall RPELN metastasis rate was 12.98% (2,133/16,427). The pooled analysis revealed significant associations between RPELN metastasis and the following factors: age under 55 years (P < 0.00001), male gender (P < 0.00001), tumor size >1 cm (P < 0.00001), multifocality (P < 0.00001), capsular invasion (P < 0.00001), vascular invasion (P < 0.00001), extra-thyroidal extension (P < 0.0001), central lymph node metastasis (P < 0.00001), lateral lymph node metastasis (P < 0.00001), Hashimoto’s thyroiditis (P = 0.002), micro-calcifications (P = 0.01), and altered echogenicity (P = 0.03). Conversely, no significant associations were observed for tumor location in the right lobe (P = 0.07), superior pole (P = 0.08), middle pole (P = 1.00), inferior pole (P = 0.28), or tumor margins (P = 0.93) (all P > 0.05). Conclusion: Factors such as age <55, male sex, tumor size >1 cm, multifocality, capsular invasion, vascular invasion, extra-thyroidal extension, central lymph node metastasis, lateral lymph node metastasis, and Hashimoto’s thyroiditis are significantly associated with RPELN metastasis. These should be carefully considered during RPELN dissection in PTC management. Presentation: Sunday, July 13, 2025

Abstract Disclosure: A.A. Khan: Alexion Pharmaceuticals, Inc., Amgen Inc, Amolyt Pharma, Ascendis Pharma. B.L. Clarke: Amolyt Pharma, Ascendis Pharma, EnteraBio, Extend Bio, Takeda. M.R. Rubin: Ascendis Pharma, MBX Biosciences. P.E. Schwarz: Aventis Pharmaceuticals, Genmab, Novo Nordisk. D.M. Shoback: Ascendis Pharma. C. Gagnon: Amgen Inc, Ascendis Pharma, Novo Nordisk, Shire, Takeda. A. Palermo: None. L.G. Abbott: Abbott Laboratories, Ascendis Pharma, Clarus, Shire, Takeda. L. Kohlmeier: Amgen Inc, Ascendis Pharma, Radius Health, Inc. E. Tsourdi: Alexion Pharmaceuticals, Inc., Ascendis Pharma, Kyowa Kirin, Takeda, UCB. F. Cetani: None. R. Jain: Amgen Inc, Ascendis Pharma. C. Zhao: Ascendis Pharma. B. Lai: Ascendis Pharma. M.A. Makara: Ascendis Pharma. J. Ukena: Ascendis Pharma. C.T. Sibley: Ascendis Pharma. A.D. Shu: Ascendis Pharma. L. Rejnmark: Amolyt Pharma, Ascendis Pharma, BridgeBio, Kyowa Kirin, Takeda. Background: Hypoparathyroidism is an endocrine disease caused by insufficient levels of parathyroid hormone (PTH) and is associated with reduced quality of life and a high comorbidity burden. Conventional therapy for hypoparathyroidism (active vitamin D and elemental calcium) aims to alleviate hypocalcemia but does not address insufficient PTH and may increase the risk of renal complications. Palopegteriparatide is a prodrug of PTH(1-34), administered subcutaneously once daily, designed to provide active PTH within the physiological range for 24 hours/day. It is approved by the Food and Drug Administration, European Commission, and Medicines and Healthcare products Regulatory Agency. This analysis evaluated the long-term efficacy and safety of palopegteriparatide in adults with chronic hypoparathyroidism through week 156 of the PaTHway trial. Methods: PaTHway is a phase 3 trial with a 26-week randomized, double-blind, placebo-controlled period followed by an ongoing open-label extension period. Serum biochemistries were assessed at baseline and regular intervals. Renal function was assessed by estimated glomerular filtration rate (eGFR). Safety assessments included 24-hour urine calcium and treatment-emergent adverse events (TEAEs). Results: At week 156, 89% (73/82) of participants remained in the trial; of those, 96% were independent from conventional therapy (no active vitamin D and ≤600 mg/day elemental calcium) and 88% had normal albumin-adjusted serum calcium levels (8.3-10.6 mg/dL) with a mean (SD) of 8.9 (0.6) mg/dL. Mean (SD) serum phosphate (3.4 [0.6] mg/dL) and calcium x phosphate product (30.6 [5.4] mg2/dL2) levels remained within normal ranges through week 156. Mean (SD) eGFR at week 156 was 78.0 (14.5) mL/min/1.73 m2, reflecting a mean (SD) increase of 8.8 (11.9) mL/min/1.73 m2 from baseline (P<0.0001); 59% and 43% of participants had an increase in eGFR of ≥5 mL/min/1.73 m2 and ≥10 mL/min/1.73 m2, respectively. Among participants with baseline eGFR <60 mL/min/1.73 m2 (n=23), the mean (SD) increase in eGFR was 14.0 (8.9) mL/min/1.73 m2 from baseline to week 156. Mean (SD) 24-hour urine calcium levels normalized with palopegteriparatide treatment, remaining below the upper limit of normal (≤250 mg/day) through week 156 (162.1 [117.8] mg/day). TEAEs were mostly grade 1 or 2, with no new safety signals identified. Conclusion: Through year 3 of the PaTHway trial, retention rate was high and palopegteriparatide demonstrated consistent longer-term safety and efficacy, which included the maintenance of serum and urine biochemistries within normal levels and sustained improvement in renal function. Presentation: Saturday, July 12, 2025

Abstract Disclosure: M. Kakakhel: None. S. Fatima: None. H. Ahmad: None. A. Ibrahim: None. W. Rahman: None. R. Haider: None. H. Jawad: None. A. Qadeer: None. M. Khawar: None. F. Ahmed: None. J. Ikram: None. R. Kirchoff: None. Background: Across the world, type 1 diabetes mellitus (T1DM) is a major health problem for teenagers and young people. This study aims to examine the incidence and prevalence of T1DM by gender in the 15-39 age range between 1990 and 2021. Methods: We analyzed data from the Global Burden of Disease (GBD) to evaluate incidence and prevalence rates of T1DM in each gender from 1990 to 2021. The Annual Percentage Change (APC) and The Annual Average Percentage Change (AAPC) was used to assess trends, with p-values determining the statistical significance. Results: From 1990 to 2021, the global prevalence of T1DM was found to be increased steadily for both genders, with the highest rates recorded in 2021: 247.32 per 100,000 for females and 246.47 per 100,000 for males. Incidence rates in 2021 showed a contrasting pattern, with males exhibiting higher rates (7.18 per 100,000) compared to females (5.98 per 100,000). AAPC analysis showed that males exhibit a faster rise in both prevalence and incidence compared to females over the study period. The difference in AAPC between males and females is more pronounced for prevalence (+0.3748%) compared to incidence (+0.1956%), with all AAPC values being statistically significant (p < 0.000001). Following the APC analysis, other significant trends were revealed. Male incidence experienced the greatest increase during 2015-2021, with an APC of +1.9033% (p < 0.000001), whereas female incidence increased most between 2011 and 2014 (APC = +1.3050%; p < 0.000001). In contrast, the most significant decline in incidence was observed in females during 1990-1992, with an APC of +0.1665% (p = 0.006799), which was the lowest increase in the dataset. For prevalence, males exhibited the highest increase during 2015-2021, with an APC of +1.3938% (p < 0.000001), whereas females had their peak increase during 2006-2009, with an APC of +0.8957% (p < 0.000001). The slowest increase in prevalence for females occurred during 2014-2019, with an APC of +0.4591% (p < 0.000001). Conclusion: The prevalence and incidence of T1DM among people aged 15-39 increased significantly between 1990 and 2021, with a greater increase in males. This highlights the need for gender-specific strategies in T1DM prevention and management, and research into the factors driving these disparities. Presentation: Sunday, July 13, 2025

Abstract Disclosure: M. Kakakhel: None. S. Fatima: None. H. Ahmad: None. M. Khan: None. A. Rai: None. A. Qadeer: None. R. Haider: None. M. Khawar: None. U. Habib: None. H. Jawad: None. J. Ikram: None. F. Ahmed: None. R. Kirchoff: None. Introduction: Type 1 Diabetes Mellitus (T1DM) is a disease that affects people all over the world. This condition causes significant morbidity, as measured by Disability-Adjusted Life Years (DALYs) and mortality rates, and its severity varies worldwide. The purpose of this study is to examine trends in T1DM-related death rates and DALYs across 26 geographical areas from 1990 to 2021 in order to provide a current picture of the disease's consequences and identify regional differences. Methods: This study examined DALYs and mortality rates per 100,000 people in individuals aged 15-39 years using data from the Global Burden of Disease Study from 1990 to 2021. Trends were assessed using the Average Annual Percentage Change (AAPC), with p-values used to define statistical significance. The study examined 26 regions with varied socioeconomic development indices (SDI). Using confidence intervals to account for data uncertainty, DALYs and mortality were examined to investigate the disease burden across time. Results: In 1990, the Middle SDI region had the highest DALYs at 298,352 (95% CI: 256,144 -349,670), which reached 382,857 (95% CI: 213,704-317,664) by 2021 (AAPC = 0.15, P-value < 0.000001). The region with the highest DALYs in 2021 was the Low-Middle SDI, with 419,772 (95% CI: 344,307- 495,496) cases (AAPC = -2.93, P-value = <0.000001). From 1990 to 2021, Oceania consistently had the lowest DALYs of 1,895 (95% CI: 1,264-2,577) and 4,210(95% CI: 3,011-5,724), respectively (AAPC= 0.15, P-value = 0.0004). Mortality rates in 1990 were highest in the Middle SDI area with 3,758 deaths (95% CI: 3,343-4,332) (AAPC= -1.23, P-value = <0.000001), but by 2021, South Asia had the highest mortality rate at 5,189(95% CI: 4,272-6,087) (AAPC= -0.49). Oceania had the lowest mortality rate of 25 deaths (95% CI 145-35) (AAPC = 0.193, P-value = <0.0004) in 1990, whereas Australasia had the lowest mortality rate of 28 deaths (95% CI 26-29) in 2021 (AAPC = -0.93, P-value = <0.000001). Conclusion: From 1990 to 2021, the global burden of type 1 diabetes—as indicated by DALYs and death rates—underwent a substantial shift, with significant rises in several regions. DALYs were highest in the Middle SDI region in 1990 but have migrated to the Low-Middle SDI region by 2021, reflecting shifting healthcare issues and demographics. Mortality rates followed a similar pattern, with South Asia and the Low-Middle SDI regions experiencing the highest rates in 2021. Over both time periods, however, Oceania and Australasia consistently had the lowest DALYs and death rates. These findings emphasise the critical need for targeted interventions in high-burden areas. Addressing these differences is crucial for decreasing the global burden of T1DM. Presentation: Sunday, July 13, 2025

Abstract Disclosure: H. Ahmad: None. S. Fatima: None. M. Kakakhel: None. I. khan: None. A. Raza: None. Z. Khan: None. R. Haider: None. A. Qadeer: None. M. Khawar: None. F. Ullah: None. H. Jawad: None. J. Ikram: None. F. Ahmed: None. R.W. Kirchoff: None. Background: Type 1 diabetes mellitus (T1DM) is an autoimmune condition, characterized by the destruction of pancreatic beta cells, resulting in lifelong dependency on insulin. It is a significant health burden in adolescents and young adults, with long-term complications affecting quality of life and survival. We aim to explore sex-stratified trends in mortality and disability-adjusted life years (DALYs) due to T1DM from 1990 to 2021. Methods: We obtained sex-stratified data for adolescents and young adults (15-39 years) with T1DM from the Global Burden of Disease (GBD) from 1990 to 2021. The mortality rates were age-standardized and expressed per 100,000 deaths. Trends were analyzed as annual percentage change (APC) and average APC (AAPC) using Joinpoint Regression. Results: From 1990 to 2021, deaths due to T1DM in adolescent and young adult males increased globally from 7,123 to 9,244 per annum, with age-standardized mortality rates (ASMRs) decreasing from 0.64 to 0.61 and standardized DALYs rising from 49.56 to 51. In females, deaths rose from 6,160 to 6,892, with ASMRs declining from 0.57 to 0.47 and DALYs declining from 47.12 to 43.11. Despite the apparent rise in deaths, ASMRs exhibited a significant decline in both sexes, with an AAPC of -0.16% (95% CI: -0.20 to -0.12) in males and -0.62% (-0.68 to -0.55) in females, four times that of in males. The DALYs showed a significant decline in females with an AAPC of -0.31% (-0.35 to -0.26) but a significant increase in males with an AAPC of 0.09% (0.04 to 0.12). Males showed the greatest APC increase in ASMRs of 1.34% from 1990 to 1994, while females showed the greatest APC increase of 0.45% from 1990 to 2000, three times less and over twice the period seen in males. This was followed by the greatest APC decline of -1.14% in females from 2001 to 2011, and a non-significant decline of -0.14% till 2021. Males experienced the greatest decline of -1.14% from 2000 to 2013. It then increased significantly from 2013 to 2018 (APC: 0.73%), followed by a significant decline of -0.62% till 2021, almost four times that in females. DALYs showed a similar trend in females with the greatest increase of 0.45% from 1990 to 2000, followed by the greatest decrease of -1.14% till 2011, and then a non-significant decline of -0.14 till 2021. Males showed the greatest increase of 1.24% from 1990 to 1994 and the greatest decrease of 0.63% from 2000 to 2013, followed by a much smaller decline. Conclusion: Although ASMRs declined, the recent decline in ASMRs in females is becoming less pronounced highlighting the importance of ongoing monitoring and improvement strategies. The disparity in DALYs between males and females also demands the need for targeted interventions addressing male-specific challenges to reduce the burden of T1DM. Presentation: Sunday, July 13, 2025

Abstract Disclosure: L. Saba: None. K. Leopold: None. A.N. Lteif: None. A. Al Nofal: None. Objectives: Glucagon-like peptide-1 receptor (GLP-1R) agonists are currently approved for the treatment of type 2 diabetes and obesity in patients aged ≥10 and ≥12 years, respectively. While studies in adults with type 1 diabetes mellitus (T1DM) suggest potential glycemic benefits of GLP-1R agonists, data on their role in pediatric patients with T1DM and concomitant obesity remains limited. This case series evaluates the safety and efficacy of GLP-1R agonists as an adjunct to insulin therapy in pediatric patients with T1DM and obesity. Methods: A single-center retrospective review examined pediatric patients with T1DM and obesity who initiated GLP-1R agonists at <18 years of age. Data were collected from chart review and analyzed from 120 days prior to GLP-1R agonist initiation until medication discontinuation, transfer of care, or January 1, 2025. Results: 5 patients (aged 12-17 years, 4 female) with T1DM and obesity all received the GLP-1R agonist semaglutide at a mean of 5.2 years post-T1DM diagnosis. 3 patients had ≥2 positive T1DM autoantibodies, 1 had positive ZnT8 antibodies only, and 1 lacked autoantibody testing. All patients were receiving insulin therapy; 4 were utilizing insulin pumps. The overall treatment duration ranged from 194-437 days (mean: 9 months), with 3 patients experiencing interruptions (42-187 days) due to insurance or supply issues. Pre- and during-treatment data were compared with a mean interval of 140 days between GLP-1R agonist start date and comparison time point (range: 69-226 days). All patients showed reductions in glucose management indicator or hemoglobin A1c by an average of 1.2%. 3 of 4 patients with available data had decreased weight-adjusted total daily insulin requirements by 30-33% (absolute dose reduction of 0.1-0.3 units/kg/day), while 1 patient had no change. Time in range increased in all 5 patients by an average of 14.2%. The average BMI change was -9%. Adverse effects included nausea, vomiting, and abdominal pain in patient 1 leading to GLP-1R agonist discontinuation; this patient also experienced 4 episodes of diabetic ketoacidosis during treatment. Increased hypoglycemia frequency was observed in patients 2, 3, and 4, however, none required glucagon administration. To mitigate hypoglycemia risk, pump settings were proactively adjusted in patients 1 and 4. Conclusions: Beyond promoting weight loss, GLP-1R agonists show promise as an adjunctive therapy in pediatric patients with T1DM and obesity by improving glycemic control and reducing insulin requirements. The observed reduction in insulin requirements per body weight suggests an underlying degree of insulin resistance in these patients. Preemptive decrease in insulin doses with each increase in GLP-1R agonist dose should be considered to mitigate hypoglycemia risk. Larger studies are needed to assess long-term safety and efficacy in the pediatric population with T1DM and obesity. Presentation: Saturday, July 12, 2025