Objective:

To evaluate the effect of initiating glucagon-like peptide-1 receptor agonist (GLP-1RA) therapy after a mild ischemic stroke on clinical outcomes in obese patients, focusing on recurrent cerebrovascular events, healthcare utilization, and survival.

Background:

Stroke is a leading cause of death and disability, with obesity as a major modifiable risk factor for both incidence and recurrence. Effective secondary prevention is critical. While GLP-1RAs were developed for glycemic control, they also reduce cardiovascular risk. Their specific impact on post-stroke outcomes, however, remains unclear due to limited trial data.

Design/Methods:

We conducted a retrospective cohort study using data from the TriNetX Research Network. Adult patients (≥18 years) with obesity and mild ischemic stroke (NIHSS 0–8) were included. Patients who initiated GLP-1RAs within one month post-stroke were compared to non-users. Propensity score matching (PSM) was applied to balance baseline characteristics. The primary outcome was recurrent stroke, with secondary outcomes including transient ischemic attack (TIA), hospital readmission, and imaging utilization within one year post-stroke.

Results:

A total of 246 patients who initiated GLP-1RA were compared to 30,629 non-users. After PSM, 243 patients were included in each cohort. GLP-1RA users had a significantly lower risk of recurrent stroke (39.5% vs. 52.7%, RR 0.750, 95% CI 0.617–0.912, p=0.004) and hospital readmission (20.2% vs. 30.5%, RR 0.662, 95% CI 0.484–0.907, p=0.009). They also had reduced head CT/MRI imaging utilization (13.6% vs. 20.6%, RR 0.660, 95% CI 0.442–0.987, p=0.040). No significant difference was observed in TIA incidence (6.6% vs. 7.0%, RR 0.941, 95% CI 0.487–1.819, p=0.857).

Conclusions:

GLP-1RA therapy following mild ischemic stroke in obese patients was associated with a lower risk of recurrent stroke, hospital readmission, and imaging use. These findings support the potential role of GLP-1RAs in secondary stroke prevention for this high-risk population. Larger prospective studies are needed to confirm these results and guide clinical recommendations.