(A-120) Association of SGLT2 Inhibitors and GLP-1 Receptor Agonists with the Risk of Parkinson’s Disease in Patients with Type 2 Diabetes: A Propensity Score-Matched Cohort Study

Background: Parkinson’s disease is a neurodegenerative disorder that has been increasingly linked to type 2 diabetes, with shared metabolic and inflammatory pathways potentially contributing to disease progression. Emerging evidence suggests that sodium-glucose cotransporter 2 inhibitors (SGLT2is) and glucagon-like peptide-1 receptor agonists (GLP-1RAs) may exert neuroprotective effects and potentially reduce the risk of Parkinson’s disease; however, the available data remain limited.

Objectives: This study aimed to investigate the association between the use of SGLT2is, GLP-1RAs, and the risk of Parkinson’s disease in individuals with type 2 diabetes, using dipeptidyl peptidase-4 inhibitors (DPP4is) as an active comparator.

Methods: This study analyzed electronic health records from the TriNetX Analytics Network, incorporating data from 64 healthcare organizations across the United States. Adults with type 2 diabetes who initiated treatment with SGLT2is, GLP-1RAs, or DPP4is between January 2018 and December 2023 were included. A target trial emulation approach was employed, and propensity score matching was used to balance baseline characteristics, including age, sex, race, comorbidities, baseline medication use, and relevant laboratory test results, separately for each of the three treatment comparisons: SGLT2is vs. DPP4is, GLP-1RAs vs. DPP4is, and SGLT2is vs. GLP-1RAs. The primary outcome was newly diagnosed Parkinson’s disease. Patients were followed for up to 5 years or until November 1, 2024. Cox proportional hazards models were applied to estimate hazard ratios (HRs) with 95% confidence intervals (CIs).

Results: A total of 442,266 patients (221,133 matched pairs) were included in the SGLT2is vs. DPP4is comparison, 536,168 patients (268,084 matched pairs) in the GLP-1RAs vs. DPP4is comparison, and 538,826 patients (269,163 matched pairs) in the SGLT2is vs. GLP-1RAs comparison. The risk of Parkinson’s disease was significantly lower among SGLT2i users compared with DPP4i users (HR: 0.82; 95% CI: 0.75–0.89) and among GLP-1RA users compared with DPP4i users (HR: 0.83; 95% CI: 0.78–0.90). In the comparison between SGLT2is and GLP-1RAs, SGLT2is were associated with a lower risk of Parkinson’s disease than GLP-1RAs (HR: 0.88; 95% CI: 0.81–0.95).

Conclusions: This study provides evidence that SGLT2is and GLP-1RAs may be associated with a reduced risk of Parkinson’s disease in patients with type 2 diabetes, suggesting potential neuroprotective effects. These findings highlight the importance of considering neurological outcomes when selecting glucose-lowering therapies. However, further research is needed to validate our results and establish causality.