PharmacoAnalytics: Assessing the Relationship Between Glucagon-like Peptide-1 Receptor Agonist (GLP-1 RA) Utilization and Dementia Incidence

Aims: To evaluate whether GLP-1 RAs, a newer generation of antidiabetic medication, will lower dementia risk compared to all other antidiabetic medications in the type 2 diabetes population. Materials and Methods: All type 2 diabetes Mellitus (T2DM) patients who dispensed antidiabetic medications from June 2005 to December 2022 in the National Alzheimer’s Coordinating Center (NACC) database entered the study. A propensity score matching a ratio of 1 to 2 was used to balance baseline covariates. Kaplan-Meier analysis was applied to compare the probability of dementia incidents over time. A Multivariate Cox regression model was performed to obtain significant predictors, presenting adjusted hazard ratios (aHR) and Confidence Intervals (CIs) for the time to dementia incidence. Results: After 1 to 2 propensity score matching, the final cohort consisted of 133 GLP-1 RA users and 266 non-users. Kaplan-Meier demonstrated that GLP-1 users were associated with a lower risk of developing dementia compared to non-users (p=0.0123). The Multivariate Cox regression model identifies GLP-1 RA (aHR 0.42, 95%Confidence Interval (CI): [0.22-0.80], p=0.009) and female (aHR: 0.50, 95%CI: [0.29-0.87], p=0.01) as protective factors for dementia, while age ( aHR: 1.07, 95%CI: [1.03-1 .10], p=0.01), 2 pairs of APOE4 genes (aHR: 2.42, 95%CI: [1.43-4.09], p=0.001), and depression (aHR: 3.30, 95%CI: [1.87-5.84], p