2841-LB: Glucagon-Like Peptide 1 Receptor Agonists Lower the Risk of Stroke and Vascular Dementia among Individuals with Obesity

Introduction and Objective: Obesity exacerbates neurovascular inflammation, increasing risks of stroke and vascular dementia (VD). Although GLP-1 RAs demonstrate stroke risk reduction in clinical trials, their real-world effectiveness in preventing VD remains unknown. We aim to determine if GLP1-RAs lower the risks of these neurological outcomes in obese population. Methods: We included obese patients from OneFlorida+ electronic health records from January 2015 to January 2024. The exposure was the initiation of GLP-1RAs. We conducted a retrospective cohort study with a target trial emulation design, applying a time-dependent propensity score to balance baseline covariates between groups. An intention-to-treat analysis was conducted to investigate the association between GLP-1RAs and neurological outcomes. The primary outcomes were stroke, VD, and secondary outcome was Alzheimer’s disease and dementia (ADRD). We applied Cox proportional hazards models to estimate the adjusted hazard ratios (HR) as well as 95% confidence interval (CI) for the time to the first occurrence of the outcomes. We performed subgroup analyses to assess the heterogeneity in treatment effects by age, sex, race and ethnicity, type 2 diabetes (T2D) status, obesity severity, and cardiovascular disease (CVD) status. Results: We included 61,880 matched individuals (mean [SD] age, 61.3 [8.2] years; 64.3% female), with 30,940 GLP-1 RA users and 30,940 non-users. Compared to non-use, GLP-RA use was associated with a lower risk of stroke (HR: 0.84 [0.76-0.93]), VD (0.56 [0.32-0.99]), and ADRD (0.74 [0.63-0.86]). In our subgroup analyses of stroke, GLP-1 RA were more beneficial in those with age <75, were female, were non-Hispanic Black, with obesity, with T2D, and without CVD. For VD, patients with age <75, female, and obese were more favored. Conclusion: GLP-1 RA use was associated with reduced risk of stroke and VD in obese individuals. Future studies are warranted to investigate whether stroke mediates the association between GLP-1 RA use and VD. Disclosure W. Chen: None. Y. Lee: None. Y. Xian: None. S. Guo: None.