The goal of this study is to test the neuroprotective effects of starting Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) within 6 months before a stroke in Type 2 Diabetes (T2D) patients
The current literature mentions GLP-1 RAs to have demonstrated cardiovascular and neuroprotective effects in T2D patients. However, whether antecedent GLP-1 RA exposure mitigates post-stroke mortality or cognitive decline is unclear.
We conducted a retrospective cohort study using the TriNetX network, utilizing CPT and ICD-10 codes. We included adults aged 50–90 years with T2D who experienced a first-ever ischemic stroke between December 2017 and June 2025. Patients with prior stroke, neurodegenerative diseases, malignancy of the brain, end-stage renal disease, or who have no follow-up within 90 days of the stroke were excluded. Cohort 1 included patients with GLP-1 RA exposure within 6 months before their first-ever stroke, while the control group had no record of GLP-1 RA use. Primary outcomes were Alzheimer’s disease, vascular and all-cause dementia, and secondary outcomes were all-cause mortality and recurrent stroke. Outcomes were measured within 7 years after the initial stroke event. Propensity score matching was done to balance demographics, vascular risk factors, antidiabetic and cardiovascular medications, and HbA1c. After matching 4,856 patients remained in each cohort, we calculated absolute risks, risk differences, risk ratios, and 95% confidence intervals. Statistical significance was defined as a p-value <0.05.
Pre-stroke GLP-1 RA users demonstrated lower Alzheimer’s disease (0.7 vs 1.1%; p = 0.035), all-cause dementia (2.5 vs 3.4%; p = 0.009), and all-cause mortality (13.3 vs 18.2%; p < 0.001) against controls. Vascular dementia and recurrent stroke showed no statistical significance.
Among T2D patients experiencing a first ischemic stroke, pre-stroke GLP-1 RA use was associated with lower post-stroke mortality and dementia, suggesting potential neuroprotective benefits. Prospective studies are needed to clarify causality and optimize post-stroke management strategies