Diabetes最新文献

{"title":"Sustained Weight Loss With Combined LEAP2 and Semaglutide Treatment in Mice","authors":"Stephanie K. Holm, Valdemar B. I. Johansen, Pablo Ranea-Robles, Charlotte Svendsen, Christoffer Merrild, Rebecca Rohlfs, Mauro Lo Conte, Wouter F. J. Hogendorf, Myrte Merkestein, Alexander N. Zaykov, Andreas M. Fritzen, Bharath K. Mani, Christoffer Clemmensen","doi":"10.2337/db24-1056","DOIUrl":"https://doi.org/10.2337/db24-1056","url":null,"abstract":"The recent identification of liver-expressed antimicrobial peptide 2 (LEAP2) as an endogenous antagonist and inverse agonist of the growth hormone secretagogue receptor (GHSR) has revived interest in targeting the ghrelin-GHSR pathway for obesity treatment. Here, we assessed the preclinical efficacy of treatment with a long-acting LEAP2 (LA-LEAP2) analog for weight loss and explored its potential as an adjunct to semaglutide to enhance weight reduction and mitigate weight regain. We found that LA-LEAP2 lowered body weight in obese mice, which was reflected in reduced energy intake and preserved energy expenditure. While not uniformly observed across all experiments, some studies demonstrated superior weight reduction with the combination of LA-LEAP2 and semaglutide compared with semaglutide monotherapy. Notably, the combination also attenuated weight regain more effectively than semaglutide alone. Importantly, no signs of discomfort or behavioral aversion were detected following LA-LEAP2 administration. Collectively, these data indicate that LEAP2 analogs have the potential to enhance the efficacy of glucagon-like peptide 1 receptor agonism and support durable weight loss. ARTICLE HIGHLIGHTS Liver-expressed antimicrobial peptide 2 (LEAP2) is an endogenous ghrelin receptor (GHSR) antagonist and inverse agonist, and represents a novel strategy to modulate the GHSR system for treatment of cardiometabolic disease. A long-acting LEAP2 (LA-LEAP2) analog induces significant weight reduction in rodent models without causing aversion. LA-LEAP2–mediated weight loss is driven by decreased energy intake alongside preservation of energy expenditure during weight loss. Combined LA-LEAP2 and semaglutide therapy supports durable weight loss, addressing a critical gap in obesity treatment.","PeriodicalId":11376,"journal":{"name":"Diabetes","volume":"66 1","pages":""},"PeriodicalIF":7.7,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144533064","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fasting Lowers Glucagon Levels Under Basal Conditions and During Insulin-Induced Hypoglycemia in Individuals With Type 1 Diabetes","authors":"Nicole Sheanon, Shana O. Warner, Yufei Dai, Nat H. Whitsett, Shahriar Arbabi, Blair Hoeting, Shailendra B. Patel, Diana Lindquist, Jason J. Winnick","doi":"10.2337/db25-0251","DOIUrl":"https://doi.org/10.2337/db25-0251","url":null,"abstract":"Short-term fasting (<24 h) is common in individuals with type 1 diabetes (T1D), but it is associated with increased risk of hypoglycemia. Current strategies to mitigate this risk include changing the timing and/or dose of insulin; however, it is unclear whether counterregulatory hormone secretion is diminished, which would also contribute to this elevated risk. The current experiments were conducted to determine whether short-term fasting affects the hormonal and hepatic responses to insulin-induced hypoglycemia in those with T1D. Nine C-peptide–negative individuals with T1D gave their informed consent to participate in a randomly assigned crossover-design metabolic trial. In one study, participants ate an isocaloric breakfast and lunch before undergoing a hyperinsulinemic/hypoglycemic metabolic challenge in the evening (FED); in the other, they fasted before the hypoglycemic challenge (FAST). Immediately before insulin-induced hypoglycemia, glucagon concentrations were 43% lower in FAST compared with FED (31 ± 5 and 54 ± 6 pg/mL, respectively; P < 0.001), and endogenous glucose production (EGP) was 28% lower (3.4 ± 0.2 and 4.6 ± 0.3 mg/kg/min, respectively; P < 0.01). During insulin-induced hypoglycemia, the area under the curve for glucagon remained lower by 42% in FAST compared with FED (1,598 ± 229 and 2,768 ± 422 pg/mL ∗ 60 min, respectively; P < 0.01), as did EGP (41 ± 4 and 78 ± 12 mg/kg ∗ 60 min, respectively; P = 0.01). These data demonstrate that fasting lowers glucagon concentrations and EGP under euglycemic/normoinsulinemic metabolic conditions and during insulin-induced hypoglycemia. This reduction in metabolic flexibility, in addition to hyperinsulinemia, enhances susceptibility to fasting-induced low blood glucose in individuals with T1D and should be considered when developing strategies to avoid hypoglycemia. Article Highlights Fasting is associated with increased risk of hypoglycemia in patients with type 1 diabetes (T1D); however, little is known about how the counterregulatory responses to low blood sugar are affected under these metabolic conditions. During insulin-induced hypoglycemia, fasting (compared with eating normal meals for breakfast and lunch) glucagon concentrations were lower by 42% and endogenous glucose production by 47% in individuals with T1D. The secretion of other counterregulatory hormones during hypoglycemia was not affected by fasting (e.g., epinephrine, norepinephrine, cortisol). Fasting diminishes glucagon levels under hypoglycemic conditions in those with T1D, which may increase their susceptibility to hypoglycemia.","PeriodicalId":11376,"journal":{"name":"Diabetes","volume":"635 1","pages":""},"PeriodicalIF":7.7,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144520338","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"T-Cell Mediated Immunity to Gliadin Is Elicited in the Gut Mucosa of Type 1 Diabetes Patients Only in Presence of Celiac Disease Comorbidity","authors":"Carmen Gianfrani, Alessandra Camarca, Stefania Picascia, Serena Vitale, Ilaria Mottola, Martina Carpinelli, Mariantonia Maglio, Silvia Gregori, Adriana Franzese, Renata Auricchio, Riccardo Troncone","doi":"10.2337/db24-1120","DOIUrl":"https://doi.org/10.2337/db24-1120","url":null,"abstract":"Type 1 diabetes (T1D) and celiac disease (CeD) are two strongly associated autoimmune disorders, as they share genetic risk factors and immunopathogenic mechanisms. Several studies suggest an implication of gluten proteins, the causative antigen of CeD, in T1D pathogenesis. We investigated whether a gliadin-specific T-cell reactivity is present in the gut mucosa of children with T1D, with or without CeD comorbidity. Thirty-three young children were enrolled (median age 10 years) and divided in five groups based on T1D and/or CeD diagnosis. All patients underwent upper endoscopy for suspicion of CeD or gastrointestinal complaints, and duodenal biopsy specimens were processed for analysis of lymphoid cells phenotype and T cell–mediated reactiveness to gliadin. No substantial differences were found in the percentages of various T-cell subsets between the groups. No gliadin T-cell reactivity was found in T1D children negative for CeD, also in the presence of antibodies neutralizing regulatory cytokines interleukin 10 and transforming growth factor β. By contrast, a marked T-cell response to gliadin was detected in T1D with either potential (positive for CeD-associated autoantibodies and normal mucosa histology) or full-blown CeD (villous atrophy). In conclusion, no adaptive immunity to gluten occurs in the small intestine of T1D children in the absence of CeD comorbidity. Article Highlights It has been hypothesized that dietary proteins act as environmental factors in type 1 diabetes pathogenesis. This study investigated whether gliadin-specific T cells are present in the small intestine of children with type 1 diabetes, without or with celiac disease comorbidity. No sign of gliadin-reactive T cells, either proinflammatory or regulatory, was observed in the gut mucosa of children with type 1 diabetes negative for celiac disease autoimmunity. Interferon-γ producing T cells were detected in gut mucosa biopsy specimens of children with diabetes seropositive for antitissue transglutaminase antibodies. Our study does not support a pathogenic role of intestinal T cell–mediated immunity to gluten in type 1 diabetes pathogenesis.","PeriodicalId":11376,"journal":{"name":"Diabetes","volume":"1 1","pages":""},"PeriodicalIF":7.7,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144479186","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"292-OR: Oral Semaglutide and Cardiovascular Outcomes by Baseline A1C and BMI in People with Type 2 Diabetes in the SOUL Trial","authors":"SILVIO E. INZUCCHI, ROHANA ABDUL GHANI, JOHN DEANFIELD, MADS D.M. ENGELMANN, G. KEES HOVINGH, OLE K. JEPPESEN, MONIKA KELLERER, KABIRDEV MANDAVYA, JOHANNES F. MANN, NIKOLAUS MARX, CHANTAL MATHIEU, DARREN K. MCGUIRE, VISWANATHAN MOHAN, SHARON L. MULVAGH, RODICA POP-BUSUI, NEIL R. POULTER, MARIA SEJERSTEN RIPA, GABRIELA ROMAN, RÓBINSON SÁNCHEZ GARCÍA, MICHAEL SHECHTER, JOHN B. BUSE","doi":"10.2337/db25-292-or","DOIUrl":"https://doi.org/10.2337/db25-292-or","url":null,"abstract":"Introduction and Objective: In SOUL (NCT03914326), oral semaglutide (sema) 14 mg QD, a GLP-1 receptor agonist, reduced major adverse cardiovascular (CV) event (MACE) risk by 14%. GLP-1RAs are routinely prescribed to reduce A1c and BMI in type 2 diabetes (T2D). Whether the CV benefits of oral sema are influenced by baseline A1c or BMI is not fully known. Methods: SOUL’s primary outcome was time to first MACE, assessed for this post hoc analysis by baseline A1c, BMI and body weight using Cox regression. Results: People with T2D (n=9650; A1c 6.5–10%) and known atherosclerotic CV disease (ASCVD) or chronic kidney disease (CKD) were randomized to oral sema or placebo and followed for a mean of 47.5 months. We found significant differences in MACE outcomes associated with oral sema use by baseline A1c, with greater effects apparent with A1c >8.0% (Fig.). When the data were further analyzed across four A1c strata, the MACE benefit from oral sema appeared to apply to those with A1c >7%. The effects of oral sema on MACE were the same in those with BMI above / below 30 kg/m2, as well as across all four BMI strata, and above / below the mean body weight (87.9 kg) (Fig.). Conclusion: In SOUL, the CV benefits of oral sema appeared more pronounced with higher A1c levels at baseline but were consistent across various BMI categories. These data may help inform the individualized use of oral sema in people with T2D and ASCVD and/or CKD. Disclosure S.E. Inzucchi: Consultant; Novo Nordisk, AstraZeneca, Boehringer-Ingelheim, Merck & Co., Inc, Pfizer Inc, Bayer Pharmaceuticals, Inc. R. Abdul Ghani: None. J. Deanfield: Other Relationship; Aegerion Pharmaceuticals, Amgen Inc, AstraZeneca, Bayer Pharmaceuticals, Inc, Boehringer-Ingelheim, Merck & Co., Inc, Novartis Pharmaceuticals Corporation, Novo Nordisk A/S, Novo Nordisk A/S, Pfizer Inc. M.D.M. Engelmann: Employee; Novo Nordisk. G. Hovingh: Employee; Novo Nordisk. Stock/Shareholder; Novo Nordisk. O.K. Jeppesen: None. M. Kellerer: Advisory Panel; Abbott, Bayer Pharmaceuticals, Inc. Speaker's Bureau; Boehringer-Ingelheim, Johnson & Johnson Medical Devices Companies. Advisory Panel; Lilly Diabetes. Speaker's Bureau; Lilly Diabetes. Advisory Panel; Novo Nordisk. Speaker's Bureau; Novo Nordisk. Advisory Panel; Sanofi. K. Mandavya: Employee; Novo Nordisk. J.F. Mann: Other Relationship; AstraZeneca, Bayer Pharmaceuticals, Inc. Advisory Panel; Novo Nordisk. Board Member; AstraZeneca, Bayer Pharmaceuticals, Inc, Boehringer-Ingelheim, Novo Nordisk. Other Relationship; Sanofi. Consultant; AstraZeneca, Bayer Pharmaceuticals, Inc, Novo Nordisk. Research Support; AstraZeneca. Other Relationship; Boehringer-Ingelheim. Research Support; Novo Nordisk, Sanofi. Speaker's Bureau; AstraZeneca, Bayer Pharmaceuticals, Inc, Novo Nordisk, Novartis AG. Other Relationship; UpToDate Inc / KDIGO. N. Marx: Speaker's Bureau; Abbott, Amgen Inc, AstraZeneca. Advisory Panel; AstraZeneca. Speaker's Bureau; Bayer Pharmaceutica","PeriodicalId":11376,"journal":{"name":"Diabetes","volume":"188 1","pages":""},"PeriodicalIF":7.7,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144370523","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Subclasses of Glucose Trajectories in Early Childhood Stratified the Risk of Abnormal Glucose Tolerance in Adolescence and Young Adulthood","authors":"Yingchai Zhang, Eric S.H. Lau, Claudia H.T. Tam, Noel Y.H. Ng, Mai Shi, Atta Y.T. Tsang, Hanbin Wu, Aimin Yang, Hongjiang Wu, Lai Yuk Yuen, Elaine Y.K. Chow, Andrea O.Y. Luk, Alice P.S. Kong, Chi Chiu Wang, Juliana C.N. Chan, Wing Hung Tam, Ronald C.W. Ma","doi":"10.2337/db25-0256","DOIUrl":"https://doi.org/10.2337/db25-0256","url":null,"abstract":"Early-life exposures may shape long-term effects on glucose regulation. This study aimed to stratify long-term abnormal glucose tolerance (AGT) risk from early childhood. A total of 906 children were enrolled at baseline and reevaluated in adolescence and young adulthood. By using the latent class trajectory analysis, glucose trajectories of children were measured via five–time point oral glucose tolerance tests and then grouped into three latent subclasses: mild excursion–normal reversion (MN), moderate excursion–delayed reversion (MD), and severe excursion–delayed reversion (SD). Logistic regression was performed to estimate the risk of AGT and associations between cardiometabolic factors and subclasses. In adolescence, compared with the MN subclass, the risk of AGT was 1.7-fold in the MD subclass and 5.5-fold in the SD subclass, after adjusting for age, sex, BMI, and Tanner stage. In young adulthood, the adjusted risk of AGT was 3.6-fold and 11.6-fold in the MD and SD subclasses, respectively. During the full natural history of glucose tolerance, the risk of AGT was 3.6-fold in the MD subclass and 18.1-fold in the SD subclass, after adjusting for childhood covariates. MD and SD subclass membership was strongly associated with childhood hypertension, maternal gestational diabetes, and maternal hypertension during pregnancy. Glucose trajectory subclasses in early childhood effectively stratified the long-term risk of AGT. The association between maternal cardiometabolic health and childhood subclass membership highlighted that prenatal exposures may influence metabolic outcomes in offspring. Article Highlights Abnormal glucose tolerance (AGT) in youth has become an alarming global public health issue; however, approaches to identify high-risk population among young people have not been well-established. Can the long-term risk of AGT be stratified by the subclasses of glucose trajectories defined in childhood? Subclasses defined in childhood can efficiently stratify the risk of AGT in adolescence and young adulthood. The subclass membership was strongly associated with cardiometabolic disorders in childhood and maternal cardiometabolic disorders during pregnancy. This subclass method provides a potential strategy to identify those at risk of later cardiometabolic disorders from childhood for more intensive evaluation of intervention. The close relationship between maternal cardiometabolic disorders and subclass membership of children highlighted the potential influence of gestational cardiometabolic health on the development of cardiometabolic disorders in offspring.","PeriodicalId":11376,"journal":{"name":"Diabetes","volume":"9 1","pages":""},"PeriodicalIF":7.7,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144370522","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Macrophage-Expressed Micropeptide Smim30 Maintains Adipose Tissue Insulin Sensitivity and Safeguards Systemic Metabolic Homeostasis","authors":"Yonghe Ma, Yu Shi, Kaiyuan Wu, Ping Li, Nikhil Gupta, Chengfei Jiang, Hang Sun, Xiangbo Ruan, Tyler Finley, Jing Wu, Chengyu Liu, Haiming Cao","doi":"10.2337/db24-0721","DOIUrl":"https://doi.org/10.2337/db24-0721","url":null,"abstract":"A growing number of micropeptides (miPs) have been identified in recent years, but their biological roles remain largely unexplored. We identified a conserved 6-kDa miP, named small integral membrane protein 30 (SMIM30), as a potential metabolic regulator. To study the physiological function of Smim30, we generated a loss-of-function mouse strain using the CRISPR/Cas9-mediated knock-in strategy. When fed both normal chow and high-fat diets, these mice exhibited elevated blood glucose and insulin levels, with reduced insulin sensitivity. We further showed that Smim30 loss in adipose tissue drove systemic insulin resistance, although intriguingly, adipocyte-expressed Smim30 was dispensable in this effect. Instead, Smim30 was mainly expressed in adipose tissue–residential macrophages, and loss of Smim30 led to increased macrophage infiltration and production of proinflammatory cytokines and chemokines. Smim30 also modulated inflammatory responses in ex vivo/in vitro macrophage systems, which are conserved in both humans and mice. The results indicate that Smim30 plays a key role in maintaining adipose tissue insulin sensitivity and safeguarding systemic metabolic homeostasis, offering potential as both a diagnostic biomarker and therapeutic target for metabolic disorders. Article Highlights Understanding the role of micropeptides (miPs) in metabolic regulation could enhance insights into metabolic diseases and open new pathways for treatment. Small integral membrane protein 30 (Smim30), an adipose tissue macrophage–expressed miP, maintains insulin sensitivity and safeguards systemic metabolic homeostasis. Smim30 modulates inflammatory responses and macrophage–adipocyte communication in adipose tissue. Smim30 could serve as a potential diagnostic biomarker and therapeutic target for metabolic disorders.","PeriodicalId":11376,"journal":{"name":"Diabetes","volume":"57 74 1","pages":""},"PeriodicalIF":7.7,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144370524","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"297-OR: Interactive Virtual Assistant for Health Promotion and Diabetes Care in Older Adults with Diabetes—A Randomized Controlled Trial","authors":"LUCAS S. MATZENBACHER, FREDERICO L. DA COSTA, LAURA G.B. DE BARROS, VICENZO GHENO, ISABELA S. MAIA, LUIZA M. BLANK, MARIA ANTÔNIA B. BRUM, LUCAS F. FONTOURA, JANINE ALESSI, GABRIELA H. TELO","doi":"10.2337/db25-297-or","DOIUrl":"https://doi.org/10.2337/db25-297-or","url":null,"abstract":"Introduction and Objective: This study evaluated the impact of an interactive virtual assistant device, programmed with a behavioral intervention model, on mental-health and diabetes-related outcomes in older adults with type 2 diabetes (T2D) Methods: We conducted a randomized controlled trial enrolling participants aged 65 years or older with T2D. Participants were randomized to receive a Smart Speaker EchoDot 3rd Gen device, programmed with a behavioral intervention that included automatic medication reminders and health tips, or to continue with usual care for 12 weeks. The primary outcome was mental distress, assessed using the SRQ-20 scale. Secondary outcomes included quality of life (measured with the SF-36 scale), adherence to diabetes self-care behaviors (assessed with the SCI-R scale), and HbA1c. An analysis of covariance model was used to evaluate the impact of the intervention on study outcomes. Between-group mean differences after the intervention period, adjusted for baseline data and relevant covariates, were reported, with statistical significance set at an alpha level of 0.05 Results: A total of 112 participants (63% female, 63% white; mean age: 72.5 years; mean T2D duration: 16.9 years; mean HbA1c: 7.9%) were randomized, with 103 completing the trial. At 12 weeks, participants in the intervention group showed a reduction in mental distress (mean difference: -1.46; 95% CI -2.73 to -0.19; p=0.024), an increase in quality of life (mean difference: 9.46; 95% CI 3.65 to 15.26; p=0.001), greater adherence to diabetes self-care behaviors (mean difference: 3.40; 95% CI 1.61 to 5.19; p<0.001), and lower HbA1c (mean difference: -0.48; 95% CI -0.85 to -0.11; p=0.011) when compared to those in the usual care group Conclusion: In this randomized controlled trial, a smart-speaker-based intervention was associated with significant improvements in mental health, quality of life, diabetes self-care behaviors, and HbA1c in older adults with T2D Disclosure L.S. Matzenbacher: None. F.L. da Costa: None. L.G.B. de Barros: None. V. Gheno: None. I.S. Maia: None. L.M. Blank: None. M.B. Brum: None. L.F. Fontoura: None. J. Alessi: None. G.H. Telo: None. Funding Brazilian National Council for Scientific and Technological Development (CNPq/MCTI/FNDCT 18/2021 grant)","PeriodicalId":11376,"journal":{"name":"Diabetes","volume":"19 1","pages":""},"PeriodicalIF":7.7,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144370516","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"291-OR: Effect of Type 2 Diabetes Characteristics on Semaglutide Treatment in People with Type 2 Diabetes and Peripheral Artery Disease—A Post Hoc Analysis of the STRIDE Trial","authors":"NEDA RASOULI, ECENUR GUDER ARSLAN, ANDREI-MIRCEA CATARIG, KIM HOULIND, BERNHARD LUDVIK, JOAKIM NORDANSTIG, HARALD SOURIJ, SEBASTIAN THOMAS, SUBODH VERMA, MARC P. BONACA","doi":"10.2337/db25-291-or","DOIUrl":"https://doi.org/10.2337/db25-291-or","url":null,"abstract":"Introduction and Objective: The STRIDE trial (NCT04560998) demonstrated that once weekly semaglutide 1.0 mg significantly improved maximum walking distance (MWD) in people with type 2 diabetes (T2D) and symptomatic peripheral artery disease (PAD) vs. placebo. Whether the benefits are consistent across T2D characteristics has not been described. Methods: The primary outcome in STRIDE, MWD measured on a constant load treadmill at 52 weeks, was analyzed by T2D duration (≥10 vs. <10 years), obesity status (BMI (≥30 vs. <30 kg/m2)), glycemic control (HbA1c (≥7% vs. <7%)), and concomitant T2D medications (SGLT2i or insulin). A mixed model for repeated measurements was employed, incorporating treatment, region, and subgroup as fixed factors, along with the treatment-by-subgroup interaction. Baseline values were used as covariates, all nested within each visit. Results: Among 792 randomized STRIDE participants at baseline, median T2D duration was 12.2 years, BMI 28.7 kg/m2, HbA1c 7.1%, with 35.1% on SGLT2i and 31.7% on insulin. Semaglutide significantly improved MWD regardless of T2D duration, BMI, HbA1c and concomitant SGLT2i or insulin use (Figure). Conclusion: These findings support the efficacy of semaglutide in patients with symptomatic PAD across the spectrum of T2D including non-obese participants and those with HbA1c <7%. Disclosure N. Rasouli: Advisory Panel; Novo Nordisk. Research Support; Novo Nordisk. Advisory Panel; Eli Lilly and Company. Research Support; Eli Lilly and Company. E. Guder Arslan: Employee; Novo Nordisk A/S, Sanofi. A. Catarig: Employee; Novo Nordisk A/S. Stock/Shareholder; Novo Nordisk A/S. K. Houlind: Consultant; LeMaitre, Novo Nordisk. B. Ludvik: Research Support; Novo Nordisk. Speaker's Bureau; Novo Nordisk. Advisory Panel; Novo Nordisk, Boehringer-Ingelheim. Speaker's Bureau; Boehringer-Ingelheim. Research Support; Amgen Inc. Speaker's Bureau; AstraZeneca. Research Support; Eli Lilly and Company. Advisory Panel; Eli Lilly and Company. Speaker's Bureau; Eli Lilly and Company. J. Nordanstig: Advisory Panel; AstraZeneca, Novo Nordisk. Other Relationship; Novo Nordisk. H. Sourij: Advisory Panel; Eli Lilly and Company. Speaker's Bureau; Eli Lilly and Company. Research Support; Eli Lilly and Company. Advisory Panel; Boehringer-Ingelheim. Speaker's Bureau; Daiichi Sankyo. Advisory Panel; Novo Nordisk A/S. Speaker's Bureau; Novo Nordisk A/S. Advisory Panel; Novartis AG, Amarin Corporation, Amgen Inc. S. Thomas: None. S. Verma: Other Relationship; Various. M.P. Bonaca: Other Relationship; CPC Clinical Research. Funding The STRIDE trial was funded by Novo Nordisk A/S","PeriodicalId":11376,"journal":{"name":"Diabetes","volume":"48 1","pages":""},"PeriodicalIF":7.7,"publicationDate":"2025-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144337522","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"173-OR: Eligibility, Impact, and Costs for Tirzepatide for the Primary Prevention of Diabetes Mellitus","authors":"JAY B. LUSK, SHANNON AYMES, EMILY OBRIEN, FAN LI","doi":"10.2337/db25-173-or","DOIUrl":"https://doi.org/10.2337/db25-173-or","url":null,"abstract":"Introduction and Objective: A recent trial of tirzepatide (SURMOUNT) found a 92% reduction of diabetes incidence among patients with overweight or obesity over three years. Our objective was to estimate the potential population, outcomes, and cost associated with use of tirzepatide for the primary prevention of DM. Methods: Data from the 2021-2023 cycle of the National Health and Nutrition Examination Survey (NHANES) were used to estimate risk reductions for the incidence of DM extrapolated from SURMOUNT results. Costs and savings (from saved diabetes care costs) of tirzepatide were estimated under current U.S. list prices, direct to patient prices, and UK list prices. Results: In total, 2,022 NHANES participants were eligible for tirzepatide therapy (51% female, 49% male, median age 53, IQR 37-66) translating to a weighted U.S. population estimate of 83,454,492 (95% CI 74,423,832 - 92,485,151). Across the lifespan, 30,522,710 cases of diabetes could be prevented if risk reduction was persistent. Projected costs/savings are shown in Table 1. Conclusion: Nearly one in three Americans are potentially eligible for tirzepatide for the primary prevention of DM. At current list price, treating the entire population could cost nearly 20 trillion dollars, offset by only 3.4 trillion dollars of savings, yielding a net cost of approximately 16 trillion dollars, or 60% of 2023 US gross domestic product; treatment at the UK list price would result in nearly 500 billion in net savings. Disclosure J.B. Lusk: None. S. Aymes: None. E. OBrien: Research Support; Pfizer Inc. F. Li: None.","PeriodicalId":11376,"journal":{"name":"Diabetes","volume":"275 1","pages":""},"PeriodicalIF":7.7,"publicationDate":"2025-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144337511","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"2043-LB: Universal Access to GLP1-RAs Could Reduce Global Obesity Prevalence by 20% and Save 28 Million Lives over Five Years—A Microsimulation Study","authors":"ELIZABETH STATON, PIAOPIAO LI, JIEUN LEE, K M VENKAT NARAYAN, MOHAMMED K. ALI, ILANA GRAETZ, HUI SHAO","doi":"10.2337/db25-2043-lb","DOIUrl":"https://doi.org/10.2337/db25-2043-lb","url":null,"abstract":"Introduction and Objective: GLP-1RA drugs have demonstrated benefits for people with type 2 diabetes mellitus (T2DM) or obesity, however, medication access is limited. This microsimulation study modeled the impact of increased access to semaglutide globally on the burden of 7 conditions. Methods: We developed and validated a microsimulation model incorporating age-, sex-, and country-specific prevalence and incidence data for T2DM, obesity, CVD, CKD, stroke, ESKD, and all-cause mortality, using data from the 2021 Global Burden of Disease and NCD-RisC studies. A simulation experiment was conducted to evaluate the effects of providing universal access to semaglutide on these key health outcomes over 5 years across 196 countries. Results: Of the worldwide adult population of approximately 6.1 billion, 19.0% met eligibility criteria for semaglutide use, based on a prevalence of 8.76% for type 2 diabetes and 16.4% for obesity. Universal access to semaglutide could reduce 5-year all-cause mortality by 7.41% (absolute change (AC): -0.29%, 95% CI: -0.47 to -0.10%; about 28M lives) and obesity prevalence by 21.9% (AC -5.42%, 95% CI: -6.48 to -4.36%; about 330M fewer obese individuals). Country specific results on all health outcomes are presented in Figure 1. Conclusion: Expanding access and affordability to GLP-1RA can significantly improve health worldwide. Disclosure E. Staton: None. P. Li: None. J. Lee: None. K. Narayan: None. M.K. Ali: Advisory Panel; Eli Lilly and Company. I. Graetz: Research Support; Pfizer Inc, PRIME Education, LLC. H. Shao: None. Funding National Institutes of Health (R01DK133465)","PeriodicalId":11376,"journal":{"name":"Diabetes","volume":"36 1","pages":""},"PeriodicalIF":7.7,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144335293","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}