Semaglutide and tirzepatide may offer neuroprotective and cerebrovascular benefits

Glucagon-like peptide 1 receptor agonists (GLP-1RAs), such as semaglutide and tirzepatide, provide cardiometabolic benefits to patients with type 2 diabetes and obesity. However, their effects on mitigating neurodegenerative and cerebrovascular diseases remain unclear.To examine this issue, researchers evaluated the association between semaglutide and tirzepatide use and the incidence of dementia, Parkinson disease, ischemic stroke, intracerebral hemorrhage and all-cause mortality, compared with other antidiabetes drugs in adults with both type 2 diabetes and obesity. The retrospective cohort study analyzed data from the TriNetX US network, a global health research network that provides electronic health records for approximately 275 million individuals across 19 countries. The study analyzed data (from December 2017 to June 2024) for adults aged 40 years or older with both type 2 diabetes and obesity who were initiating semaglutide, tirzepatide or other antidiabetes drugs. The study excluded adults with prior neurodegenerative or cerebrovascular diseases. Propensity score matching was used to balance the baseline characteristics.Patients treated with antidiabetes drugs were categorized into two groups: users of GLP-1RAs (semaglutide or tirzepatide) or users of other antidiabetic drugs (biguanides, sulfonylureas, dipeptidyl peptidase 4 inhibitors, sodium-glucose cotransporter 2 inhibitors, thiazolidinediones or α-glucosidase inhibitors).The primary outcomes were the incidence of neurodegenerative diseases (dementia, Parkinson disease, and mild cognitive impairment) and cerebrovascular diseases (stroke and intracerebral hemorrhage). The secondary outcome was all-cause mortality. Cox proportional hazard models were used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs). Results showed the following:A total of 60,860 adults with type 2 diabetes and obesity were included in the study.After propensity score matching, each of the two study groups included 30,430 adults—GLP-1RA group (mean age, 57.9 years; 50.2% female) and the other antidiabetes drug group (mean age, 58.0 years; 51.4% female).During seven years of 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) compared to the other antidiabetes drug group. No significant differences between the two groups were noted in the risk of Parkinson disease or intracerebral hemorrhage.Subgroup analyses revealed greater dementia, stroke and all-cause mortality benefits in patients aged 60 years or older, women, and patients with a body mass index of 30–40.The authors conclude that in this cohort study, use of GLP-1RAs (semaglutide or tirzepatide) was associated with a lower risk of dementia, stroke and all-cause mortality compared to other classes of antidiabetes drugs in adults with both type 2 diabetes and obesity. These findings suggest potential neuroprotective and cerebrovascular benefits of GLP-1RAs and a potential role in mitigating neurodegenerative and cerebrovascular risks in this high-risk population. Further trials are warranted to confirm these outcomes.Reference:Lin HT, Tsai YF, Liao PL, et al. Neurodegeneration and stroke after semaglutide and tirzepatide in patients with diabetes and obesity. JAMA Netw Open 2025;8;(7):e2521016. Published Online: July 15, 2025. (accessed July 17, 2025).

Semaglutide and tirzepatide may offer neuroprotective and cerebrovascular benefits

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