750-P: Association of Glucagon-Like Peptide 1 Receptor Agonists with Incident Parkinson’s Disease in U.S. Older Adults with Type 2 Diabetes

Background: Previous studies suggested the possibility of disease-modifying effects for glucagon-like peptide-1 receptor agonists (GLP-1RAs), but the evidence on the association between GLP-1RAs and risk of Parkinson’s disease(PD) remains to be clarified.

Methods: This population-based new-user cohort study included individuals with T2D who were newly prescribed a GLP-1RA or a dipeptidyl peptidase 4 inhibitor (DPP4i) using Medicare administrative data from Jan 2016 to Dec 2020. The primary endpoint was a new diagnosis of PD. A stabilized inverse probability of treatment weighting (sIPTW) - adjusted Cox proportional hazards regression was employed to estimate the hazard ratio (HR) of PD and 95% confidence intervals (CI) between GLP-1RA users and DPP4i users. Stratified analyses were performed, such as by age, sex, race/ethnicity, glucose-lowering drug (GLD) use at baseline, obesity at baseline, and molecule of GLP-1RA.

Results: A total of 89,074 Medicare beneficiaries who initiated either GLP-1RA inhibitor (n=30,091) or DPP4i (n=58,983) were included in the analysis. The crude incidence rate of PD was lower among GLP-1RA users (2.85 cases per 1000 person-years) when compared to DPP4i users (3.92 cases per 1000 person-years). An sIPTW-adjusted Cox model showed that GLP-1RA users were associated with a 23% lower risk of PD than DPP4i users (HR, 0.77; 95%CI, 0.63-0.95). Our findings were largely consistent across different subgroup analyses except for GLD use at baseline. A significantly lower risk of PD was observed among those using insulin at baseline and those with no GLD use at baseline, while no significant difference was detected among the groups using 1 GLD at baseline and ≥ 2 GLDs at baseline.

Conclusion: New use of GLP-1RAs was significantly associated with a lower risk of PD compared to new use of DPP4i in a large cohort of older adults with T2D.