GLP-1 Receptor Agonist Treatment Linked to Lower Stroke and Dementia Risk in Those with Diabetes and Obesity

Treatment with the glucagon-like peptide 1 (GLP-1) receptor agonists semaglutide and tirzepatide for people with type 2 diabetes and obesity may significantly lower risk of stroke, all-cause mortality, and dementia. The new findings, published in JAMA Network Open, suggest that treatment with GLP-1 receptor agonists may have neuroprotective and cerebrovascular benefits beyond glycemic control, with a potential role in broader neurologic and cerebrovascular risk reduction.

In the retrospective cohort study, researchers analyzed the health records of 60,860 adult participants aged ≥40 years with a diagnosis of type 2 diabetes and obesity who were enrolled in the TriNetX platform between 2004 and 2017. Within this population, new users of semaglutide or tirzepatide treatment (n=30,430) were propensity score–matched to those initiating other antidiabetic medications (n=30,430). The incidence of cerebrovascular diseases and incidence of neurodegenerative diseases were the primary outcomes of the study.

After 7 years of follow-up (mean [SD], 1.77 years [1.35]), compared with other antidiabetic medications, GLP-1 receptor agonist treatment was associated with a significant reduction in the risk of:

• Dementia (hazard ratio [HR], 0.63; 95% CI, 0.50 to 0.81)
• Stroke (HR, 0.81; 95% CI, 0.70 to 0.93)
• All-cause mortality (HR, 0.70; 95% CI, 0.63 to 0.78)

There were no significant differences in intracerebral hemorrhage or Parkinson disease (PD) risk associated with semaglutide and tirzepatide treatment. Additionally, subgroup analysis revealed that GLP-1 receptor agonist treatment was significantly associated with a reduced risk of other dementia (HR, 0.69; 95% CI, 0.56 to 0.84), but not AD or vascular dementia. The authors note that the insights of the subgroup analysis regarding statistical significance may result from a smaller population size for the AD and vascular dementia subgroups, and that further, large-scale studies are necessary.