Semaglutide, Tirzepatide Cut Dementia, Stroke Risk in Type 2 Diabetes

Treatment with the glucagon-like peptide 1 receptor agonists (GLP-1 RAs) semaglutide or tirzepatide was associated with significantly lower risks of dementia, stroke, and all-cause mortality compared with other antidiabetic medications among a large cohort of patients with type 2 diabetes (T2D) and obesity.1 These findings suggest that the benefits of GLP-1 RAs may extend beyond glycemic control, offering important protection against neurodegenerative and cerebrovascular diseases.

This retrospective cohort study is published in JAMA Network Open.

Glucagon-like peptide 1 receptor agonists may offer neuroprotective and survival benefits beyond blood sugar control, a study finds. | Image credit: DedMityay - stock.adobe.com

“The aim of this study was to assess the incidence of dementia, Parkinson disease, stroke, intracerebral hemorrhage, and all-cause mortality among patients treated with semaglutide or tirzepatide vs. other antidiabetic drugs using electronic health record–based data,” wrote the researchers of the study.

Although GLP-1 RAs are primarily used to treat T2D and obesity, growing evidence suggests they may also reduce the risk of dementia.2 A previous study found that GLP-1 RAs were linked to a significant decrease in dementia incidence, unlike pioglitazone or sodium-glucose cotransporter protein 2 (SGLT2) inhibitors. However, another large study involving nearly 397,000 patients found both GLP-1 RAs and SGLT2 inhibitors were associated with reduced risk of Alzheimer disease and related dementias, with similar effect sizes. These mixed findings and short follow-up periods underscore the need for longer, more targeted studies about the neuroprotective potential of GLP-1 RAs.

The researchers utilized electronic health record data from December 1, 2017, to June 30, 2024.1 Adults 40 years or older with T2D and obesity who initiated treatment with either semaglutide, tirzepatide, or other antidiabetic drugs were included, excluding individuals with prior diagnoses of neurodegenerative or cerebrovascular diseases.

Patients were categorized into 2 groups: those receiving GLP-1 RAs and those receiving other antidiabetic agents, including biguanides, sulfonylureas, dipeptidyl peptidase-4 inhibitors, SGLT2 inhibitors, thiazolidinediones, and α-glucosidase inhibitors.

Primary outcomes included the incidence of dementia, Parkinson disease, mild cognitive impairment, ischemic stroke, and intracerebral hemorrhage, while all-cause mortality served as a secondary outcome.

The study included 60,860 adults with T2D and obesity. Over a follow-up period of up to 7 years, patients in the GLP-1 RA group experienced significantly lower risks 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 with those receiving other antidiabetic treatments.

No significant differences were observed in the risks of Parkinson disease or intracerebral hemorrhage. Additionally, subgroup analyses indicated that the protective effects of GLP-1 RAs were most pronounced in individuals 60 years or older, women, and patients with a body mass index between 30 and 40.

However, the researchers noted several study limitations. First, it was an observational analysis. Second, the TriNetX database lacked biomarker, genetic, and neuroimaging data. Third, medication exposure was based on prescriptions without confirmation of adherence or dosing. Additionally, the analysis did not account for death as a competing risk, although all-cause mortality was included as a secondary outcome. Therefore, the researchers acknowledged that future randomized trials are needed to confirm these findings.

Despite these limitations, the researchers believe the study findings suggest the potential role of GLP-1 RAs in minimizing dementia and stroke risk in patients with T2D and obesity.

“In this cohort study, we found electronic health record–based evidence that the use of GLP-1RAs, particularly semaglutide and tirzepatide, is associated with a lower incidence of dementia, stroke, and all-cause mortality in patients with both type 2 diabetes and obesity, suggesting potential neuroprotective and cerebrovascular benefits,” wrote the researchers.

References

1. 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

2. Anderer S. GLP-1 medications may lower dementia risk, research shows. JAMA. 2025;333(21):1855. doi:10.1001/jama.2025.5640