Diabetes care最新文献

{"title":"Gradual Titration of Semaglutide Results in Better Treatment Adherence and Fewer Adverse Events: A Randomized Controlled Open-Label Pilot Study Examining a 16-Week Flexible Titration Regimen Versus Label-Recommended 8-Week Semaglutide Titration Regimen.","authors":"Roy Eldor, Noa Avraham, Orit Rosenberg, Miriam Shpigelman, Avivit Golan-Cohen, Tali Cukierman-Yaffe, Eugene Merzon, Assaf Buch","doi":"10.2337/dc25-0690","DOIUrl":"https://doi.org/10.2337/dc25-0690","url":null,"abstract":"<p><strong>Objective: </strong>To determine whether a slower, flexible titration regimen of semaglutide would improve adherence and reduce gastrointestinal adverse events (GI-AEs) compared with the label-recommended regimen in patients with type 2 diabetes (T2D).</p><p><strong>Research design and methods: </strong>A total of 104 patients with T2D were randomized to label-recommended titration (0.25 mg, 0.5 mg, 1 mg at 4-week intervals) or flexible titration (starting at 0.0675 mg [measured as five clicks made by the dose selector dial], with gradual increases by 0.0675 mg/week and delays for GI-AEs) for 26 weeks.</p><p><strong>Results: </strong>While final doses were similar between groups, only 2% of patients in the flexible arm withdrew due to GI-AEs vs. 19% in the label arm (P = 0.005). The flexible arm reported less nausea (45.1% vs. 64.2%; P = 0.051) and asthenia (9.8% vs. 24.5%; P = 0.047), with fewer days experiencing nausea (2.88 vs. 6.3 days; P = 0.017). HbA1c and BMI changes were similar between groups.</p><p><strong>Conclusions: </strong>Slower, flexible titration improved adherence and reduced adverse events without compromising efficacy.</p>","PeriodicalId":93979,"journal":{"name":"Diabetes care","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144651644","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Understanding Patient Preferences Regarding Limb Salvage for Diabetic Foot Ulcers: A Discrete Choice Experiment.","authors":"Lyndsay M O'Hara, Alison D Lydecker, Gwen L Robinson, Nathan N O'Hara, Justin J Kim, Alyson J Littman, Brian M Schmidt, Odessa Addison, David J Margolis, Mary-Claire Roghmann","doi":"10.2337/dc25-0478","DOIUrl":"10.2337/dc25-0478","url":null,"abstract":"<p><strong>Objective: </strong>Diabetic foot ulcers (DFUs) often lead to amputations. Limb salvage aims to preserve the lower extremity, but the complexity of care and uncertainty of healing can delay patients' return to normal activities. This study aimed to understand military veterans' preferences regarding limb salvage for DFUs, using a discrete choice experiment (DCE).</p><p><strong>Research design and methods: </strong>A DCE was conducted with 98 veterans with diabetes at the Baltimore Veterans Affairs Medical Center. Participants were presented with 10 choice sets involving different levels of postrecovery mobility, amputation levels, and future surgery risks. These attributes were developed through literature review and interviews. Data were analyzed using a multinomial logit model to estimate the utility of each attribute level and assess preference heterogeneity.</p><p><strong>Results: </strong>The study population was older (mean age 69 years), Black (61%), and male (94%). Half (53%) had a prior foot complication. Postrecovery mobility was the most important attribute (relative importance 53%), followed by amputation level (30%) and future surgery risk (18%). Veterans valued mobility highly, with significant utility differences between walking unaided and needing a wheelchair or scooter. They were willing to accept higher amputation levels to improve mobility.</p><p><strong>Conclusions: </strong>Postrecovery mobility is a critical factor for veterans with DFUs, outweighing concerns about amputation level and future surgical risks. It should be a focus of shared decision-making. The study is limited by its single-site setting and study population. Broader research is needed. Understanding patient preferences through DCE can inform more patient-centered approaches to DFU management, potentially improving outcomes and satisfaction.</p>","PeriodicalId":93979,"journal":{"name":"Diabetes care","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144556199","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A New Simulation Model to Estimate the Long-term Health and Cost Outcomes of Interventions for People With Type 1 Diabetes.","authors":"Carolina Barbosa, Thomas J Hoerger, Nicole A Mack, Georgiy V Bobashev, Simon Neuwahl, Rainer Hilscher, Trevor Orchard, Tina Costacou, Rachel G Miller, Ralph D'Agostino, Ping Zhang","doi":"10.2337/dc25-0124","DOIUrl":"https://doi.org/10.2337/dc25-0124","url":null,"abstract":"<p><strong>Objective: </strong>To develop a U.S.-based microsimulation model for assessing the cost-effectiveness of interventions to manage type 1 diabetes.</p><p><strong>Research design and methods: </strong>We developed risk equations for 14 diabetes-related complications and mortality, 12 risk factor progression equations, and one equation for utilities associated with 14 complications using data from the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) studies and the Epidemiology of Diabetes Complications (EDC) study. We integrated all equations into a simulation model. We conducted internal and external validation and demonstrated the utility of the model using a real-world example. Main model-generated outcomes included cumulative incidence of diabetes-related complications, life years, quality-adjusted life years, medical costs, and incremental cost-effectiveness ratios.</p><p><strong>Results: </strong>The model generates long-term clinical and economic outcomes from changes in risk factors of type 1 diabetes complications. Internal validation comparing modeled outcomes to observed data used to develop the model yielded good prediction accuracy, with mean absolute percentage error across all complications of 9% and correlation of cumulative failure rates above 0.9. External validation results were mixed, with occurrence of slight under- or overprediction across complications and studies. We illustrated the model with a case study estimating the effects of expanding the use of an insulin pump with continuous glucose monitoring to all people with type 1 diabetes.</p><p><strong>Conclusions: </strong>Our new comprehensive type 1 diabetes simulation model can generate valid and accurate results for assessing the long-term cost-effectiveness of interventions to manage type 1 diabetes in the U.S.</p>","PeriodicalId":93979,"journal":{"name":"Diabetes care","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144556241","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of SGLT2 Inhibition on Glucosuria During a Hyperglycemic Clamp in HNF1A-MODY (MODY3) and Type 2 Diabetes.","authors":"Henrik Maagensen, Johanne S Jensen, Stine O Høyerup, Anne C B Thuesen, Jesper Krogh, Jens J Holst, Henrik Vestergaard, Peter Rossing, Torben Hansen, Filip K Knop, Sofie Hædersdal, Tina Vilsbøll","doi":"10.2337/dc25-0737","DOIUrl":"https://doi.org/10.2337/dc25-0737","url":null,"abstract":"<p><strong>Objective: </strong>Pathogenic variants of HNF1A cause maturity-onset diabetes of the young type 3 (HNF1A-MODY; also known as MODY3). Individuals with HNF1A-MODY are primarily treated with sulfonylureas; however, little is known about the effect of sodium-glucose cotransporter 2 (SGLT2) inhibitors in HNF1A-MODY. Interestingly, HNF1A-MODY is associated with increased glucosuria, which has been attributed to lower expression of SGLT2 as observed in HNF1A-knockout mice. We investigated the impact of acute SGLT2 inhibition on glucosuria in individuals with HNF1A-MODY or type 2 diabetes.</p><p><strong>Research design and methods: </strong>In a randomized, double-blind, crossover study, individuals with HNF1A-MODY or type 2 diabetes underwent two three-step hyperglycemic clamps targeted at 1-h periods of 10, 14, and 18 mmol/L glucose with and without acute SGLT2 inhibition (25 mg empagliflozin or placebo administrated 2 h before clamp procedures).</p><p><strong>Results: </strong>Eleven individuals with HNF1A-MODY (age [mean ± SD] 49 ± 15 years; glomerular filtration rate [GFR; mean ± SD] 113 ± 18 mL/min) and 10 individuals with type 2 diabetes (age 63 ± 7 years; GFR 103 ± 27 mL/min) were included. During the 3-h hyperglycemic clamp, SGLT2 inhibition increased urinary glucose excretion in both groups (HNF1A-MODY: 24.5 g [95% CI 20.6, 28.3]; type 2 diabetes: 23.5 g [95% CI 20.4, 26.5]). The effect of SGLT2 inhibition was not significantly different between the groups (1.0 g [95% CI -3.5, 5.6]; P = 0.6).</p><p><strong>Conclusions: </strong>The robust effect of SGLT2 inhibition on urinary glucose excretion in participants with HNF1A-MODY points to SGLT2 inhibition as a relevant glucose-lowering treatment strategy in individuals with HNF1A-MODY.</p>","PeriodicalId":93979,"journal":{"name":"Diabetes care","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144556198","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of Hospitalizations With Randomized Glycemia-Lowering Treatment in GRADE.","authors":"Daniel S Hsia, Naji Younes, Alokananda Ghosh, Erin J Kazemi, Heidi Krause-Steinrauf, John B Buse, Chelsea Baker, Janet Brown-Friday, Elsa Diaz, Jamie Diner, Erik J Groessl, Elizabeth A Legowski, Cary N Mariash, Andrea H Waltje, Deborah J Wexler, Catherine L Martin","doi":"10.2337/dc24-2839","DOIUrl":"10.2337/dc24-2839","url":null,"abstract":"<p><strong>Objective: </strong>To compare rates of and risk factors for hospitalizations among Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study (GRADE) participants taking metformin and randomly assigned to insulin glargine U-100, glimepiride, liraglutide, or sitagliptin.</p><p><strong>Research design and methods: </strong>Intention-to-treat (ITT) (N = 5,047) and on-assigned-treatment (AT) (N = 4,830) data sets were used. Baseline differences between those hospitalized versus those not hospitalized were assessed. Kaplan-Meier analysis was used to determine incidence for time to first hospitalization, and log-rank tests were used to determine treatment group differences. Time-to-event analyses were used to examine factors affecting subsequent hospitalization risk.</p><p><strong>Results: </strong>During GRADE, 1,636 participants (32.4%) were hospitalized at least once and 751 (14.9%) were hospitalized more than once. Hospitalized participants were older, less likely to be Hispanic, more likely to be White, and more likely to have a history of hypertension and had higher baseline BMI. There were no treatment group differences in incidence for time to first hospitalization in the ITT data set (P = 0.148), but a reduced hazard rate was observed for those taking liraglutide versus those taking glimepiride in the AT data set (hazard ratio 0.78 [95% CI 0.66, 0.92]; P = 0.022). Factors increasing the risk for subsequent hospitalizations included meeting the secondary outcome (HbA1c >7.5%, confirmed), each prior hospitalization, and change from assigned treatment (29%, 41%, and 56% increase in risk, respectively). Assignment to liraglutide versus glimepiride reduced this risk by 13%.</p><p><strong>Conclusions: </strong>Hospitalizations were common in GRADE, and rates were nearly identical across treatment groups. The small, but significant, reduction in risk for subsequent hospitalizations among participants assigned to liraglutide versus glimepiride may influence treatment decisions in populations similar to GRADE participants.</p>","PeriodicalId":93979,"journal":{"name":"Diabetes care","volume":" ","pages":"1288-1294"},"PeriodicalIF":0.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12178615/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144153094","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"GLP-1R Polymorphisms Modify the Relationship Between Exposure to Gestational Diabetes Mellitus and Offspring BMI Growth: The EPOCH Study.","authors":"Kylie K Harrall, Deborah H Glueck, Leslie A Lange, Elizabeth M Litkowski, Lauren A Vanderlinden, Iain R Konigsberg, Melanie G Cree, Wei Perng, Dana Dabelea","doi":"10.2337/dc25-0194","DOIUrl":"10.2337/dc25-0194","url":null,"abstract":"<p><strong>Objective: </strong>Exposure to maternal gestational diabetes mellitus (GDM) is associated with childhood BMI. Among youth, we explored whether three different glucagon-like peptide 1 receptor gene (GLP-1R) polymorphisms modified the associations between 1) GDM and BMI trajectories and 2) GDM and markers of glucose-insulin homeostasis.</p><p><strong>Research design and methods: </strong>For 464 participants from the Exploring Perinatal Outcomes Among Children (EPOCH) study, microarray genotyping was performed during childhood (∼10 years). BMI trajectories across childhood and adolescence were characterized using repeated measurements from research visits and medical record abstraction. Markers of glucose-insulin homeostasis were derived from one oral glucose tolerance test in adolescence (∼16 years). Linear models assessed effect modification by GLP-1R polymorphisms.</p><p><strong>Results: </strong>Among youth with at least one minor allele of rs10305420 (CT or TT) or rs1042044 (CA or AA), but not among major allele homozygotes, exposure to GDM was associated with higher average BMI. For rs6923761, participants who were exposed to GDM and were major allele homozygotes (i.e., genotype GG) had significantly higher average BMI than all other participants in the cohort. No polymorphisms modified the association between GDM and markers of glucose-insulin homeostasis during adolescence.</p><p><strong>Conclusions: </strong>GLP-1R polymorphisms modify the association between GDM and BMI growth among youth. Further studies are needed to replicate these findings, and to better understand the mechanisms by which GLP-1R polymorphisms lead to heterogeneity in offspring BMI growth.</p>","PeriodicalId":93979,"journal":{"name":"Diabetes care","volume":" ","pages":"1280-1287"},"PeriodicalIF":0.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12178627/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144182587","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Physical Activity Is Associated With Improved Glycemic Outcomes in Newly Diagnosed Youth With Type 1 Diabetes: 4T Exercise Program.","authors":"Dessi P Zaharieva, Victor Ritter, Franziska K Bishop, Manisha Desai, Ananta Addala, Priya Prahalad, Michael C Riddell, David M Maahs","doi":"10.2337/dc25-0765","DOIUrl":"https://doi.org/10.2337/dc25-0765","url":null,"abstract":"<p><strong>Objective: </strong>The Teamwork, Targets, Technology, and Tight Range (4T) Exercise Program evaluated physical activity patterns across the first year of type 1 diabetes diagnosis and whether physical activity was associated with changes in glucose outcomes in the 24 h following physical activity.</p><p><strong>Research design and methods: </strong>The 4T Exercise Program started newly diagnosed youth with type 1 diabetes on a continuous glucose monitoring (CGM) system and physical activity tracker around 1 month postdiagnosis. A subset of youth opted to participate in up to four quarterly structured exercise education sessions to increase their knowledge around safe physical activity.</p><p><strong>Results: </strong>Ninety-eight youth with type 1 diabetes (median [interquartile range (IQR)] age of 13 [12-15] years, 45% female, 44% non-Hispanic White) completed the study. Compared with sedentary days, days with ≥10 min of vigorous intensity physical activity were associated with an increase in time in range (TIR) of 2.3% (1.4-3.2%; P < 0.001), a decrease in time above range (TAR) of 3.1% (2.2-4.0%; P < 0.001), and an increase in time below range (TBR) of 0.8% (0.6-0.9%; P < 0.001) in the 24 h following physical activity. From 1-3 months to 10-12 months postdiagnosis, the median (IQR) step count increased by 1,134 (445-1,519) steps per day (P < 0.001), while daily moderate-to-vigorous physical activity increased by 11 (2-23) min per day (P < 0.001).</p><p><strong>Conclusions: </strong>In the 24 h following physical activity as compared with sedentary days, TIR improved, TAR was lower, and TBR remained within clinical target recommendations. For youth with new-onset type 1 diabetes, each structured exercise education session was associated with a further 0.79% increase in TIR.</p>","PeriodicalId":93979,"journal":{"name":"Diabetes care","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144546630","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assessing Neighborhood Deprivation Reveals Rural-Urban Disparities in CGM Access Among Children With Type 1 Diabetes.","authors":"Daniel R Tilden, Christie A Befort, Brent Lockee, Amey Wagemode, David Williams, Mark A Clements","doi":"10.2337/dc25-0077","DOIUrl":"10.2337/dc25-0077","url":null,"abstract":"","PeriodicalId":93979,"journal":{"name":"Diabetes care","volume":" ","pages":"e88-e90"},"PeriodicalIF":0.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12178611/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144113150","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"High Transepidermal Water Loss at the Site of Wound Closure Is Associated With Increased Recurrence of Diabetic Foot Ulcers: The NIDDK Diabetic Foot Consortium TEWL Study.","authors":"Chandan K Sen, Gayle M Gordillo, Sashwati Roy, Jordan Jahnke, Mithun Sinha, Lava Timsina, Shomita S Mathew-Steiner, Michael S Conte, Crystal Holmes, Teresa L Z Jones, Rodica Pop-Busui, Giselle Kolenic, Cathie Spino, Geoffrey C Gurtner","doi":"10.2337/dc25-0300","DOIUrl":"10.2337/dc25-0300","url":null,"abstract":"<p><strong>Objective: </strong>The National Institute of Diabetes and Digestive and Kidney Diseases Diabetic Foot Consortium tested the hypothesis that compromised restoration of the skin barrier function of closed diabetic foot ulcers (DFUs), as measured by high transepidermal water loss (TEWL), is associated with an increased risk of DFU recurrence.</p><p><strong>Research design and methods: </strong>This was a multicenter noninterventional study measuring TEWL in 418 adult participants with diabetes and a recently healed DFU. TEWL was measured at the center of the closed wound and at an anatomically similar reference area on the contralateral foot within 2 weeks of wound closure (visit 1); measurements were repeated at a wound closure confirmation visit 2 weeks later (visit 2). Participants were observed for up to 16 weeks to assess for wound recurrence. Participant self-reported and clinician assessments of DFU wound recurrence were recorded.</p><p><strong>Results: </strong>DFU recurrence by week 16 occurred in 21.5% of participants. Mean TEWL at the center of the healed DFU at visit 1 was higher for those with recurrence compared with those without (P = 0.006). Among participants with high TEWL (>30.05 g · m-2 · h-1), 35% reported wound recurrence by 16 weeks versus 17% of those with low TEWL. The odds ratio for recurrence for participants with high TEWL was 2.66 (P < 0.001). Self-reported wound recurrence was highly concordant with clinician assessment of wound recurrence.</p><p><strong>Conclusions: </strong>Compromised wound healing mechanisms culminating in wound closure associated with defective skin barrier function is associated with increased risk of DFU recurrence. Measurement of TEWL has value as a predictor of functional wound healing and could affect clinical practice, leading to better outcomes.</p>","PeriodicalId":93979,"journal":{"name":"Diabetes care","volume":" ","pages":"1233-1240"},"PeriodicalIF":16.6,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12178626/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144188661","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Differential Effect of GLP-1 Receptor Agonists and SGLT2 Inhibitors on Lower-Extremity Amputation Outcomes in Type 2 Diabetes: A Nationwide Retrospective Cohort Study.","authors":"Alexander T Hong, Ivan Y Luu, Forest Lin, Laura Shin, Chiu-Hsieh Hsu, Chia-Ding Shih, David G Armstrong, Tze-Woei Tan","doi":"10.2337/dc25-0292","DOIUrl":"https://doi.org/10.2337/dc25-0292","url":null,"abstract":"<p><strong>Objective: </strong>To compare the risk of lower-extremity amputations (LEAs) between new users of glucagon-like peptide 1 receptor agonists (GLP-1RAs) versus sodium-glucose cotransporter 2 inhibitors (SGLT2is).</p><p><strong>Research design and methods: </strong>This retrospective cohort study used TriNetX, a federated electronic health records network, including adults with type 2 diabetes who initiated GLP-1RAs or SGLT2is between May 2013 and March 2025. Propensity score matching (1:1) was used to balance demographics, comorbidities, medications, and laboratory values. Major (above-ankle) amputation-free survival was evaluated using Kaplan-Meier curves, while risks of major and minor LEAs, diabetic foot ulcers (DFUs), and mortality were estimated using hazard ratios (HRs) with 95% confidence intervals (CIs).</p><p><strong>Results: </strong>The matched cohorts included 180,740 GLP-1RA and 180,740 SGLT2i recipients. At 3 years, the GLP-1RA cohort was associated with greater major amputation-free survival (99.69% vs. 99.64%, P = 0.001) compared with the SGLT2i cohort. Additionally, GLP-1RA treatment was associated with a lower risk of major LEAs (HR 0.77 [95% CI 0.66, 0.90]), minor LEAs (HR 0.73 [95% CI 0.63, 0.84]), DFUs (HR 0.92 [95% CI 0.87, 0.96]), and mortality (HR 0.66 [95% CI 0.63, 0.69]). Risk reduction for major LEA remained significant in individuals with peripheral artery disease (HR 0.68 [95% CI 0.56, 0.82]) and DFUs (HR 0.70 [95% CI 0.58, 0.84]).</p><p><strong>Conclusions: </strong>GLP-1RA treatment was associated with greater major amputation-free survival compared with SGLT2i in people with type 2 diabetes, particularly in high-risk subgroups. Prospective studies are needed to confirm findings and inform selection of glucose-lowering therapies for people at risk for diabetes-related amputations.</p>","PeriodicalId":93979,"journal":{"name":"Diabetes care","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144487556","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}