JAMA Netw Open

GLP-1 RAs may protect against dementia, stroke in patients with diabetes and obesity

July 29, 2025

Study details. This retrospective cohort study analyzed 60,860 adults aged ≥40 years with T2DM and obesity, using EHRs from the TriNetX US network (2017–2024). After propensity score matching, 30,430 patients each initiated semaglutide or tirzepatide (GLP-1 RAs) or other antidiabetic drugs (biguanides, sulfonylureas, DPP-4is, SGLT2is, thiazolidinediones, α-glucosidase inhibitors). Primary outcomes: incident dementia, Parkinson disease (PD), mild cognitive impairment, ischemic stroke, and intracerebral hemorrhage (ICH); secondary outcome: all-cause mortality. Median follow-up: 7 years.

Results. GLP-1 RA users had significantly lower risks of dementia (hazard ratio [HR], 0.63; 95% confidence interval [CI], 0.50–0.81), ischemic 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 other antidiabetic drug users. No significant differences were observed for PD or ICH. Subgroup analyses suggested greater benefit in patients ≥60 years, women, and those with BMI 30–40.

Clinical impact. Semaglutide and tirzepatide may confer neuroprotective and cerebrovascular benefits beyond glycemic control in adults with T2DM and obesity, supporting their use in these patient populations.

Source:

Lin HT, et al. (2025, July 15). JAMA Netw Open. Neurodegeneration and Stroke After Semaglutide and Tirzepatide in Patients With Diabetes and Obesity. https://pubmed.ncbi.nlm.nih.gov/40663350/