{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T16:00:40Z","timestamp":1780588840226,"version":"3.54.1"},"reference-count":40,"publisher":"American Diabetes Association","issue":"1","license":[{"start":{"date-parts":[[2025,11,13]],"date-time":"2025-11-13T00:00:00Z","timestamp":1762992000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.diabetesjournals.org\/content\/license"}],"funder":[{"DOI":"10.13039\/501100001353","name":"National Kidney Foundation","doi-asserted-by":"publisher","award":["Young Investigator Award"],"award-info":[{"award-number":["Young Investigator Award"]}],"id":[{"id":"10.13039\/501100001353","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["R01DK115534"],"award-info":[{"award-number":["R01DK115534"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["R01DK139324"],"award-info":[{"award-number":["R01DK139324"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,1,1]]},"abstract":"<jats:sec>\n                    <jats:title>OBJECTIVE<\/jats:title>\n                    <jats:p>Glucagon-like peptide 1 agonists (GLP-1s) compared with dipeptidyl peptidase 4 inhibitors (DPP-4s) are associated with reduced risk of dementia in the general population with diabetes, but whether this association is true for patients requiring hemodialysis is unknown.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESEARCH DESIGN AND METHODS<\/jats:title>\n                    <jats:p>Using the U.S. Renal Data System and Medicare Parts A, B, and D claims data from 2011 to 2021, we used the active comparator, new-user design to evaluate incident dementia comparing GLP-1s versus DPP-4s among individuals with both diabetes and hemodialysis dependence. We used inverse probability of treatment weights (IPTW) to balance baseline characteristics and Fine-Gray models to estimate subdistribution hazard ratios (sHRs) accounting for competing risks of death and kidney transplantation. We estimated intention-to-treat and as-treated effects.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>We identified 3,619 GLP-1 users and 11,502 DPP-4 users. After IPTW, the average individual was 63 years old, 63% were White, and mean BMI was 31 kg\/m2. The median (interquartile interval) follow-up was 1.5 (0.6\u20132.9) years, and 2,014 patients received a dementia diagnosis. In the intention-to-treat analysis, the IPTW-sHR for dementia was 0.82 (95% CI 0.67\u20130.98), and after 2 years of follow-up, the cumulative incidence of dementia was 10.2% on GLP-1s vs 11.2% on DPP-4s. As-treated and subgroup analyses were consistent. GLP-1s were also associated with an increased risk of ketoacidosis (sHR 1.52, 95% CI 1.14\u20132.02; 2-year cumulative incidence: 3.1% vs. 2.2%).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS<\/jats:title>\n                    <jats:p>In patients with diabetes requiring hemodialysis, GLP-1s (vs. DPP-4s) may be a promising therapy to reduce the risk of dementia.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.2337\/dc25-1836","type":"journal-article","created":{"date-parts":[[2025,11,13]],"date-time":"2025-11-13T21:11:14Z","timestamp":1763068274000},"page":"128-136","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":2,"title":["GLP-1s Versus DPP-4s and Risk of Dementia in Patients Requiring Hemodialysis: A Target Trial Emulation Study"],"prefix":"10.2337","volume":"49","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3231-6758","authenticated-orcid":false,"given":"Dustin","family":"Le","sequence":"first","affiliation":[{"name":"Division of Nephrology, Thomas Jefferson University 1 , Philadelphia, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Kilpatrick","sequence":"additional","affiliation":[{"name":"Department of Medicine, Thomas Jefferson University 2 , Philadelphia, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Walter K.","family":"Kraft","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Physiology, and Cancer Biology, Thomas Jefferson University 3 , Philadelphia, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Morgan E.","family":"Grams","sequence":"additional","affiliation":[{"name":"Division of Precision Medicine, New York University 4 , New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernard G.","family":"Jaar","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Johns Hopkins School of Medicine 5 , Baltimore, MD"},{"name":"Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health 6 , Baltimore, MD"},{"name":"Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins Bloomberg School of Public Health 7 , Baltimore, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jung-Im","family":"Shin","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health 6 , Baltimore, MD"},{"name":"Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins Bloomberg School of Public Health 7 , Baltimore, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1167","published-online":{"date-parts":[[2025,11,13]]},"reference":[{"key":"2026060411114977800_B1","doi-asserted-by":"crossref","first-page":"101580","DOI":"10.1016\/j.eclinm.2022.101580","article-title":"Global and regional projections of the economic burden of Alzheimer\u2019s disease and related dementias from 2019 to 2050: a value of statistical life approach","volume":"51","author":"Nandi","year":"2022","journal-title":"EClinicalMedicine"},{"key":"2026060411114977800_B2","doi-asserted-by":"crossref","first-page":"1339","DOI":"10.2215\/CJN.10150917","article-title":"Dementia, Alzheimer\u2019s disease, and mortality after hemodialysis initiation","volume":"13","author":"McAdams-DeMarco","year":"2018","journal-title":"Clin J Am Soc Nephrol"},{"key":"2026060411114977800_B3","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1186\/s13195-019-0486-z","article-title":"Risk of dementia in patients with end-stage renal disease under maintenance dialysis\u2014a nationwide population-based study with consideration of competing risk of mortality","volume":"11","author":"Kuo","year":"2019","journal-title":"Alzheimers Res Ther"},{"key":"2026060411114977800_B4","doi-asserted-by":"crossref","first-page":"504678","DOI":"10.1155\/2015\/504678","article-title":"The role of oxidative damage in the pathogenesis and progression of Alzheimer\u2019s disease and vascular dementia","volume":"2015","author":"Luca","year":"2015","journal-title":"Oxid Med Cell Longev"},{"key":"2026060411114977800_B5","doi-asserted-by":"crossref","first-page":"3075","DOI":"10.2337\/dci22-0027","article-title":"Diabetes management in chronic kidney disease: a consensus report by the American Diabetes Association (ADA) and Kidney Disease: improving Global Outcomes (KDIGO)","volume":"45","author":"de Boer","year":"2022","journal-title":"Diabetes Care"},{"key":"2026060411114977800_B6","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1001\/jamaneurol.2025.0360","article-title":"Cardioprotective glucose-lowering agents and dementia risk: a systematic review and meta-analysis","volume":"82","author":"Seminer","year":"2025","journal-title":"JAMA Neurol"},{"key":"2026060411114977800_B7","doi-asserted-by":"crossref","first-page":"102689","DOI":"10.1016\/j.eclinm.2024.102689","article-title":"Comparative effectiveness of glucagon-like peptide-1 agonists, dipeptidyl peptidase-4 inhibitors, and sulfonylureas on the risk of dementia in older individuals with type 2 diabetes in Sweden: an emulated trial study","volume":"73","author":"Tang","year":"2024","journal-title":"EClinicalMedicine"},{"key":"2026060411114977800_B8","article-title":"Effects of Single-Dose Semaglutide on Cognition and Energy in Healthy Volunteers","volume-title":"ClinicalTrials.Gov.","author":"University of Oxford","year":"2024"},{"key":"2026060411114977800_B9","unstructured":"Novo Nordisk A\/S\n          . Randomised Double-Blind Placebo-Controlled Clinical Trial Investigating the Effect and Safety of Oral Semaglutide in Subjects With Early Alzheimer\u2032s Disease (EVOKE Plus). In: ClinicalTrials.Gov.Bethesda, MD, National Library of Medicine, 2025. NLM Identifier: NCT04777409. Accessed 13 April 2025. Available from https:\/\/clinicaltrials.gov\/study\/NCT04777409"},{"key":"2026060411114977800_B10","article-title":"A Randomised Double-Blind Placebo-Controlled Clinical Trial Investigating the Effect and Safety of Oral Semaglutide in Subjects With Early Alzheimer\u2032s Disease (EVOKE). In:","volume-title":"ClinicalTrials.Gov.","author":"Novo Nordisk A\/S","year":"2025"},{"key":"2026060411114977800_B11","unstructured":"U.S. Renal Data System\n          . 2021 USRDS Annual Data Report: Epidemiology of Kidney Disease in the United States.Bethesda, MD, National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, 2021"},{"key":"2026060411114977800_B12","doi-asserted-by":"crossref","first-page":"126","DOI":"10.2337\/dc22-0659","article-title":"Antihyperglycemic medication use among U.S. adults with hemodialysis-dependent kidney disease and comorbid diabetes","volume":"45","author":"Klein","year":"2022","journal-title":"Diabetes Care"},{"key":"2026060411114977800_B13","article-title":"October \u2013 December 2019 | Potential Signals of Serious Risks\/New Safety Information Identified by the FDA Adverse Event Reporting System (FAERS)","author":"U.S. Food and Drug Administration"},{"key":"2026060411114977800_B14","unstructured":"Medicines & Healthcare products Regulatory Agency\n          . GLP-1 receptor agonists: reports of diabetic ketoacidosis when concomitant insulin was rapidly reduced or discontinued. Accessed 17 April 2025. Available from https:\/\/www.gov.uk\/drug-safety-update\/glp-1-receptor-agonists-reports-of-diabetic-ketoacidosis-when-concomitant-insulin-was-rapidly-reduced-or-discontinued"},{"key":"2026060411114977800_B15","doi-asserted-by":"crossref","first-page":"e221169","DOI":"10.1001\/jamanetworkopen.2022.1169","article-title":"Association of glucagon-like peptide-1 receptor agonist vs dipeptidyl peptidase-4 inhibitor use with mortality among patients with type 2 diabetes and advanced chronic kidney disease","volume":"5","author":"Chen","year":"2022","journal-title":"JAMA Netw Open"},{"key":"2026060411114977800_B16","doi-asserted-by":"crossref","first-page":"1100","DOI":"10.2215\/CJN.0000000750","article-title":"GLP-1 receptor agonist outcomes, safety, and body mass index change in a national cohort of patients on dialysis","volume":"20","author":"Orandi","year":"2025","journal-title":"Clin J Am Soc Nephrol"},{"key":"2026060411114977800_B17","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1053\/j.ajkd.2023.07.024","article-title":"Trial emulation methods","volume":"83","author":"Shin","year":"2024","journal-title":"Am J Kidney Dis"},{"key":"2026060411114977800_B18","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1038\/ki.2009.413","article-title":"An improved comorbidity index for outcome analyses among dialysis patients","volume":"77","author":"Liu","year":"2010","journal-title":"Kidney Int"},{"key":"2026060411114977800_B19","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1093\/ckj\/sfab158","article-title":"An introduction to inverse probability of treatment weighting in observational research","volume":"15","author":"Chesnaye","year":"2022","journal-title":"Clin Kidney J"},{"key":"2026060411114977800_B20","doi-asserted-by":"crossref","first-page":"S84","DOI":"10.1016\/j.jclinepi.2013.01.013","article-title":"Prognostic score-based balance measures can be a useful diagnostic for propensity score methods in comparative effectiveness research","volume":"66","author":"Stuart","year":"2013","journal-title":"J Clin Epidemiol"},{"key":"2026060411114977800_B21","doi-asserted-by":"crossref","first-page":"4391","DOI":"10.1002\/sim.7501","article-title":"Practical recommendations for reporting Fine-Gray model analyses for competing risk data","volume":"36","author":"Austin","year":"2017","journal-title":"Stat Med"},{"key":"2026060411114977800_B22","unstructured":"R Core Team.\n          \n          R: a Language And Environment for Statistical Computing. R Foundation for Statistical Computing, Vienna, Austria, 2020"},{"key":"2026060411114977800_B23","unstructured":"StataCorp\n          . Stata Statistical Software: Release 17. College Station, TX, StataCorp LLC, 2021"},{"key":"2026060411114977800_B24","doi-asserted-by":"crossref","first-page":"268","DOI":"10.7326\/M16-2607","article-title":"Sensitivity analysis in observational research: introducing the E-value","volume":"167","author":"VanderWeele","year":"2017","journal-title":"Ann Intern Med"},{"key":"2026060411114977800_B25","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1056\/NEJMoa1603827","article-title":"Liraglutide and cardiovascular outcomes in type 2 diabetes","volume":"375","author":"Marso","year":"2016","journal-title":"N Engl J Med"},{"key":"2026060411114977800_B26","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1056\/NEJMoa2107519","article-title":"Tirzepatide versus semaglutide once weekly in patients with type 2 diabetes","volume":"385","author":"Fr\u00edas","year":"2021","journal-title":"N Engl J Med"},{"key":"2026060411114977800_B27","doi-asserted-by":"crossref","first-page":"2247","DOI":"10.1056\/NEJMoa1509225","article-title":"Lixisenatide in patients with type 2 diabetes and acute coronary syndrome","volume":"373","author":"Pfeffer","year":"2015","journal-title":"N Engl J Med"},{"key":"2026060411114977800_B28","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1038\/s44220-025-00390-x","article-title":"An analysis on the role of glucagon-like peptide-1 receptor agonists in cognitive and mental health disorders","volume":"3","author":"De Giorgi","year":"2025","journal-title":"Nat Mental Health"},{"key":"2026060411114977800_B29","doi-asserted-by":"crossref","first-page":"e70161","DOI":"10.1002\/alz.70161","article-title":"Glycated hemoglobin and body mass index as mediators of GLP-1RAs and Alzheimer\u2019s disease and related dementias in patients with type 2 diabetes","volume":"21","author":"Tang","year":"2025","journal-title":"Alzheimers Dement"},{"key":"2026060411114977800_B30","doi-asserted-by":"crossref","first-page":"778","DOI":"10.1001\/jamainternmed.2025.1189","article-title":"Glucose-lowering medications, glycemia, and cognitive outcomes: the GRADE randomized clinical trial","volume":"185","author":"Luchsinger","year":"2025","journal-title":"JAMA Intern Med"},{"key":"2026060411114977800_B31","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1016\/j.clinthera.2014.11.008","article-title":"Effect of glucagon-like peptide-1 receptor agonists on lipid profiles among type 2 diabetes: a systematic review and network meta-analysis","volume":"37","author":"Sun","year":"2015","journal-title":"Clin Ther"},{"key":"2026060411114977800_B32","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1056\/NEJMoa043545","article-title":"Atorvastatin in patients with type 2 diabetes mellitus undergoing hemodialysis","volume":"353","author":"Wanner","year":"2005","journal-title":"N Engl J Med"},{"key":"2026060411114977800_B33","doi-asserted-by":"crossref","first-page":"1248","DOI":"10.2337\/dc19-0120","article-title":"The association of late-life diabetes status and hyperglycemia with incident mild cognitive impairment and dementia: the ARIC study","volume":"42","author":"Rawlings","year":"2019","journal-title":"Diabetes Care"},{"key":"2026060411114977800_B34","unstructured":"Fondation H\u00f4pital Saint-Joseph\n          . Efficacy and Tolerance of Liraglutide for Weight Loss in Obese Type 2 Diabetic Hemodialysis Patients. In: ClinicalTrials.Gov.Bethesda, MD, National Library of Medicine, 2023. NLM Identifier: NCT04529278. Accessed 29 March 2025. Available from https:\/\/clinicaltrials.gov\/study\/NCT04529278"},{"key":"2026060411114977800_B35","unstructured":"Lingvay\n              I\n            \n          . Semaglutide for Dialysis-Treated Patients - a Glucose Time in Range Study- DIALYSIS-TIR Study. In: ClinicalTrials.Gov.Bethesda, MD, National Library of Medicine, 2024. NLM Identifier: NCT06042153. Accessed 28 January 2025. Available from https:\/\/clinicaltrials.gov\/study\/NCT06042153"},{"key":"2026060411114977800_B36","doi-asserted-by":"crossref","first-page":"1798","DOI":"10.1681\/ASN.0000000693","article-title":"Glycemia assessed by continuous glucose monitoring among people treated with maintenance dialysis","volume":"36","author":"de Boer","year":"2025","journal-title":"J Am Soc Nephrol"},{"key":"2026060411114977800_B37","doi-asserted-by":"crossref","first-page":"134","DOI":"10.2337\/dc21-0957","article-title":"Risk of incident dementia according to glycemic status and comorbidities of hyperglycemia: a nationwide population-based cohort study","volume":"45","author":"Kim","year":"2022","journal-title":"Diabetes Care"},{"key":"2026060411114977800_B38","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1159\/000064928","article-title":"Diabetes mellitus and the risk of dementia, Alzheimer\u2019s disease and vascular cognitive impairment in the Canadian Study of Health and Aging","volume":"14","author":"MacKnight","year":"2002","journal-title":"Dement Geriatr Cogn Disord"},{"key":"2026060411114977800_B39","doi-asserted-by":"crossref","first-page":"1258","DOI":"10.7326\/ANNALS-24-02648","article-title":"Glucagon-like peptide-1 receptor agonists and incidence of dementia among older adults with type 2 diabetes: a target trial emulation","volume":"178","author":"Inoue","year":"2025","journal-title":"Ann Intern Med"},{"key":"2026060411114977800_B40","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1097\/WAD.0000000000000164","article-title":"Validity of death certificate and hospital discharge ICD codes for dementia diagnosis: the multi-ethnic study of atherosclerosis","volume":"31","author":"Fujiyoshi","year":"2017","journal-title":"Alzheimer Dis Assoc Disord"}],"container-title":["Diabetes Care"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/diabetesjournals.org\/care\/article-pdf\/49\/1\/128\/846806\/dc251836.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/diabetesjournals.org\/care\/article-pdf\/49\/1\/128\/846806\/dc251836.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T15:12:04Z","timestamp":1780585924000},"score":1,"resource":{"primary":{"URL":"https:\/\/diabetesjournals.org\/care\/article\/49\/1\/128\/163800\/GLP-1s-Versus-DPP-4s-and-Risk-of-Dementia-in"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,13]]},"references-count":40,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,11,13]]},"published-print":{"date-parts":[[2026,1,1]]}},"URL":"https:\/\/doi.org\/10.2337\/dc25-1836","relation":{"has-preprint":[{"id-type":"doi","id":"10.2337\/figshare.30438470","asserted-by":"object"},{"id-type":"doi","id":"10.2337\/figshare.30438470.v1","asserted-by":"object"}]},"ISSN":["0149-5992","1935-5548"],"issn-type":[{"value":"0149-5992","type":"print"},{"value":"1935-5548","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,13]]}}}