The study aimed to evaluate whether semaglutide and tirzepatide were linked to reduced rates of neurodegenerative and cerebrovascular conditions compared to other antidiabetic therapies. Using data from the TriNetX U.S. network between December 2017 and June 2024, the researchers analyzed records of over 60,000 adults aged 40 and above. All participants had type 2 diabetes and obesity, with no prior history of neurological or cerebrovascular disease at baseline.
The 60,860 patients were divided equally into two groups: one treated with semaglutide or tirzepatide, and the other with various non-GLP-1RA antidiabetic drugs.
The study led to the following findings:
- GLP-1RA users had a 37% lower risk of developing dementia compared to those on other antidiabetic drugs.
- Stroke risk reduced by 19% in patients treated with semaglutide or tirzepatide.
- All-cause mortality was 30% lower among individuals using GLP-1RAs.
- There were no significant differences in the incidence of Parkinson’s disease or intracerebral hemorrhage between the two groups.
- Subgroup analyses showed greater benefits in patients aged 60 years and older.
- Women experienced more pronounced positive outcomes from GLP-1RA therapy.
- Patients with a body mass index between 30 and 40 showed enhanced treatment benefits.
- These results suggest potential neuroprotective properties of GLP-1RAs beyond their metabolic and cardiovascular advantages.
While the study offers compelling real-world evidence, the authors caution that these are observational findings. Potential confounders such as patient frailty or adherence to prescribed medications could not be fully accounted for, and the lack of neuroimaging or biomarker data further limits definitive conclusions. Moreover, while prescriptions were tracked, actual medication use and dosage were not verified.
Despite these limitations, the study emphasizes the promising role of semaglutide and tirzepatide in reducing long-term risks associated with neurological and cerebrovascular conditions in a high-risk population. The authors recommend that future randomized clinical trials incorporate cognitive testing, neuroimaging, and detailed assessments of physical and functional health to better understand the underlying mechanisms.
The authors concluded, "The findings support the growing body of evidence suggesting that GLP-1 receptor agonists like semaglutide and tirzepatide may do more than regulate blood glucose—they could also play a critical role in preserving cognitive and neurological health in individuals living with type 2 diabetes and obesity."
Reference:
Lin H, Tsai Y, Liao P, Wei JC. Neurodegeneration and Stroke After Semaglutide and Tirzepatide in Patients With Diabetes and Obesity. JAMA Netw Open. 2025;8(7):e2521016. doi:10.1001/jamanetworkopen.2025.21016
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