TREATMENT with semaglutide or tirzepatide in adults with type 2 diabetes and obesity is associated with a significantly lower risk of dementia, stroke, and all-cause mortality compared to other antidiabetic drugs, according to new research.
Type 2 diabetes and obesity are established risk factors not only for adverse cardiovascular events but also for neurodegenerative and cerebrovascular diseases, including dementia and stroke. As glucagon-like peptide 1 receptor agonists (GLP-1RAs), such as semaglutide and tirzepatide, become increasingly central to diabetes care owing to their cardiometabolic benefits, there is growing interest in their potential to offer broader protection against neurological and cerebrovascular complications in this vulnerable population.
This large-scale retrospective cohort study drew on electronic health record data for 60,860 adults aged 40 years or older with both type 2 diabetes and obesity enrolled in the TriNetX US network between December 2017 and June 2024. After excluding individuals with pre-existing neurodegenerative or cerebrovascular disease, the study compared 30,430 patients using GLP-1RA therapy (semaglutide or tirzepatide) with 30,430 patients prescribed other antidiabetic agents—including biguanides, sulfonylureas, dipeptidyl peptidase 4 inhibitors, and sodium-glucose cotransporter 2 inhibitors—using propensity score matching to control for baseline differences. Over up to seven years of follow-up, those treated with semaglutide or tirzepatide had a 37% lower risk of developing dementia (hazard ratio [HR] 0.63, 95% CI 0.50–0.81), a 19% lower risk of stroke (HR 0.81, 95% CI 0.70–0.93), and a 30% lower risk of all-cause mortality (HR 0.70, 95% CI 0.63–0.78), compared to those on other antidiabetic drugs. No significant differences were detected in the incidence of Parkinson disease or intracerebral haemorrhage. Subgroup analyses indicated that the greatest benefits were observed among older adults (aged 60+ years), women, and those with a BMI between 30 and 40.
These findings suggest that semaglutide and tirzepatide may confer important neuroprotective and cerebrovascular advantages beyond their established effects on glycaemic control and cardiovascular risk reduction. For clinical practice, GLP-1RAs may be a particularly attractive treatment option in patients with type 2 diabetes and obesity who are at increased risk of dementia or stroke, potentially improving long-term cognitive and survival outcomes. Future randomised controlled trials are needed to substantiate these associations, clarify the underlying mechanisms, and guide patient selection for optimal benefit.
Reference
Lin H et al. Neurodegeneration and stroke after semaglutide and tirzepatide in patients with diabetes and obesity. JAMA Netw Open. 2025;8(7):e2521016.
