GLP-1 receptor agonists like semaglutide and tirzepatide are linked to significantly lower risks of dementia, ischemic stroke, and all-cause mortality in adults with type 2 diabetes and obesity, according to a large US cohort study.
In a retrospective analysis of more than 60,000 patients aged 40 years and older, researchers found that individuals initiating treatment with GLP-1 receptor agonists had better long-term neurological and survival outcomes than those taking other classes of antidiabetic drugs. The study, conducted using electronic health records from the TriNetX network between 2017 and 2024, excluded patients with prior neurodegenerative or cerebrovascular conditions and used propensity score matching to balance baseline characteristics.
Patients receiving semaglutide or tirzepatide had a 37% lower risk of developing dementia (HR, 0.63; 95% CI, 0.50–0.81), a 19% lower risk of ischemic 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) over a follow-up period of up to seven years. No significant differences were observed in the rates of Parkinson disease or intracerebral hemorrhage.
Subgroup analyses suggested that older adults, women, and those with a body mass index between 30 and 40 may derive the greatest benefit from GLP-1RA therapy in terms of neuroprotection and stroke prevention.
While these findings support the expanding role of GLP-1RAs beyond glycemic and cardiometabolic control, the authors caution that randomized trials are needed to establish a causal relationship and assess long-term safety for neuroprotective outcomes. Nevertheless, the results underscore a growing interest in leveraging metabolic therapies for brain health in high-risk populations.
Reference:
Lin H-T et al. Neurodegeneration and Stroke After Semaglutide and Tirzepatide in Patients With Diabetes and Obesity. JAMA Netw Open. 2025;8(7):e2521016.
