{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T09:36:44Z","timestamp":1791020204854,"version":"4.1.0"},"reference-count":56,"publisher":"American Medical Association (AMA)","issue":"7","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Netw Open"],"abstract":"\n Importance<\/jats:title>\n Glucagon-like peptide 1 receptor agonists (GLP-1RAs), such as semaglutide and tirzepatide, provide cardiometabolic benefits to patients with type 2 diabetes and obesity, but their potential benefits in mitigating neurodegenerative and cerebrovascular diseases remain unclear.<\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n To evaluate the association of semaglutide and tirzepatide with the incidence of dementia, Parkinson disease, ischemic stroke, intracerebral hemorrhage, and all-cause mortality compared with other antidiabetic drugs in adults with type 2 diabetes and obesity.<\/jats:p>\n <\/jats:sec>\n \n Design, Setting, and Participants<\/jats:title>\n This retrospective cohort study analyzed electronic health record\u2013based data from the TriNetX US network (December 1, 2017, to June 30, 2024) in adults aged 40 years or older with type 2 diabetes and obesity initiating semaglutide, tirzepatide, or other antidiabetic drugs, excluding those with prior neurodegenerative or cerebrovascular diseases. Propensity score matching was used to balance the baseline characteristics.<\/jats:p>\n <\/jats:sec>\n \n Exposures<\/jats:title>\n Patients treated with antidiabetic drugs were categorized as GLP-1RA (semaglutide or tirzepatide) or other antidiabetic drug (biguanides, sulfonylureas, dipeptidyl peptidase 4 inhibitors, sodium-glucose cotransporter 2 inhibitors, thiazolidinediones, and \u03b1-glucosidase inhibitors) users.<\/jats:p>\n <\/jats:sec>\n \n Main Outcomes and Measures<\/jats:title>\n The primary outcomes were the incidence of neurodegenerative diseases (dementia, Parkinson disease, and mild cognitive impairment) and cerebrovascular (stroke and intracerebral hemorrhage) diseases, while the secondary outcome was all-cause mortality. Cox proportional hazard models were used to estimate hazard ratios (HRs) with 95% CIs.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n A total of 60 860 adults with type 2 diabetes and obesity were included, with 30\u202f430 each in the GLP-1RA group (mean [SD] age, 57.9 [9.9] years; 50.2% female) and the other antidiabetic drug group (mean [SD] age, 58.0 [10.8] years; 51.4% female) after propensity score matching. During a 7-year follow-up, GLP-1RA users had a lower risk of dementia (HR, 0.63; 95% CI, 0.50-0.81), stroke (HR, 0.81; 95% CI, 0.70-0.93), and all-cause mortality (HR, 0.70; 95% CI, 0.63-0.78), with no significant differences in the risk of Parkinson disease or intracerebral hemorrhage. Subgroup analyses revealed greater benefits in patients aged 60 years or older, women, and patients with a body mass index of 30 to 40.<\/jats:p>\n <\/jats:sec>\n \n Conclusions and Relevance<\/jats:title>\n In this cohort study, the use of GLP-1RAs semaglutide and tirzepatide was associated with a lower risk of dementia, stroke, and all-cause mortality in adults with type 2 diabetes and obesity. These findings suggest potential neuroprotective and cerebrovascular benefits of GLP-1RAs beyond glycemic control, warranting further trials to confirm these outcomes.<\/jats:p>\n <\/jats:sec>","DOI":"10.1001\/jamanetworkopen.2025.21016","type":"journal-article","created":{"date-parts":[[2025,7,15]],"date-time":"2025-07-15T15:00:20Z","timestamp":1752591620000},"page":"e2521016","source":"Crossref","is-referenced-by-count":47,"title":["Neurodegeneration and Stroke After Semaglutide and Tirzepatide in Patients With Diabetes and Obesity"],"prefix":"10.1001","volume":"8","author":[{"given":"Huan-Tang","family":"Lin","sequence":"first","affiliation":[{"name":"Department of Anesthesiology, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan"},{"name":"College of Medicine, Chang Gung University, Taoyuan, Taiwan"},{"name":"Neuroscience Research Center, Chang Gung Memorial Hospital at Linkou, Taoyuan, 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