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- Although previous research has suggested that GLP-1 receptor agonists (GLP-1RAs) may have a disease-modifying effect on the development of Parkinson’s disease (PD), the results of the population studies have not been consistent. The current study compared the risk of PD in older adults (age, ≥66 years) with type 2 diabetes (N = 89,074) based on whether they received GLP-1RAs (n = 30,091) or dipeptidyl peptidase 4 inhibitors (DPP4is; n = 58,983) using Medicare administrative data from 2016 to 2020. The crude incidence rate of PD was lower among GLP-1RA users than among DPP4i users. GLP-1RA users had a 23% lower risk of PD than DPP4i users.
- The study concluded that the new use of GLP-1RAs was significantly associated with a decreased risk of PD compared with DPP4is consistently across sex, race, and GLP-1RA types.
Abstract 
Background
Previous studies have suggested that glucagon-like peptide-1 receptor agonists (GLP-1RAs) may have a disease-modifying effect in the development of Parkinson’s disease (PD), but population studies yielded inconsistent results.
Objective
The aim was to compare the risk of PD associated with GLP-1RAs compared to dipeptidyl peptidase 4 inhibitors (DPP4i) among older adults with type 2 diabetes (T2D).
Methods
Using U.S. Medicare administrative data from 2016 to 2020, we conducted a population-based cohort study comparing the new use of GLP-1RA with the new use of DPP4i among adults aged ≥66 years with T2D. The primary endpoint was a new diagnosis of PD. A stabilized inverse probability of treatment weighting (sIPTW)–adjusted Cox proportional hazards regression model was employed to estimate the hazard ratio (HR) and 95% confidence intervals (CI) for PD between GLP-1RA and DPP4i users.
Results
This study included 89,074 Medicare beneficiaries who initiated either GLP-1RA (n = 30,091) or DPP4i (n = 58,983). The crude incidence rate of PD was lower among GLP-1RA users than DPP4i users (2.85 vs. 3.92 patients 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 such as sex, race, and molecular structure of GLP-1RA.
Conclusion
Among Medicare beneficiaries with T2D, the new use of GLP-1RAs was significantly associated with a decreased risk of PD compared to the new use of DPP4i. © 2024 International Parkinson and Movement Disorder Society.
