(088) Association of Glucagon-Like Peptide-1 Receptor Agonists with Parkinson’s Disease: Scandinavian Cohort Study

Background: Type 2 diabetes has been associated with an increased risk of development of Parkinson’s disease as well as a more rapid disease progression. Growing evidence suggests that glucagon-like peptide-1 (GLP-1) receptor agonists modulate pathophysiological mechanisms of relevance for the development of Parkinson’s disease. However, the association between use of GLP-1 receptor agonists and the risk of Parkinson’s disease remains uncertain.

Objectives: To investigate the association between use of GLP-1 receptor agonists and incident Parkinson’s disease.

Methods: We conducted a cohort study using data from nationwide registers in Denmark, Norway and Sweden. Patients aged 45 years or more, who initiated a GLP-1 receptor agonist or a sulfonylurea, between 1st of January 2007 to 31st December 2021 in Denmark and Sweden; and 1st of January 2010 to 31st of December 2018 in Norway were included. The primary outcome was a first diagnosis of Parkinson’s disease captured in the national patient registers in the inpatient or outpatient setting. Cox proportional hazards regression was used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs). We used standardized mortality ratio weighting based on a propensity score to control for confounding.

Results: The cohort included 158 961 new users of GLP-1 receptor agonists and 188 065 new users of sulfonylureas. Mean age of the study population was 65 years and 43% were female. The median (IQR) follow-up time was 2.5 (1.0-5.2) years for users of GLP-1 receptor agonists and 5.8 (2.8-9.0) years for users of sulfonylureas. The adjusted incidence rate for a first diagnosis of Parkinson’s disease was 5.2 per 10000 person-years with use of GLP-1 receptor agonists and 8.0 per 10000 person-years with use of sulfonylureas (adjusted HR 0.81 [95% CI 0.68-0.96]). The results were similar in an analysis in which a lag-time period of 24 months between the index date and the start of follow-up was employed (adjusted HR 0.84 [95% CI 0.70-1.02]). In an analysis in which patients who previously had used a dipeptidyl peptidase-4 (DPP4) inhibitor, which like GLP-1 receptor agonists target the incretin system, were excluded and patients that initiated a DDP4 inhibitor during follow-up were censored the adjusted HR was 0.74 (95% CI 0.60-0.93). Hazard ratios in analyses by sex (women: adjusted HR 0.86 [95% CI 0.62-1.18] and men: adjusted HR 0.77 [95% CI 0.62-0.95]) and age group (45 to < 70 years: adjusted HR 0.84 [95% CI 0.67-1.05] and ≥70 years: adjusted HR 0.89 [95% CI 0.67-1.16]) were similar to those observed in the primary analyses.

Conclusions: In this large cohort study use of GLP-1 receptor agonists compared with use of sulfonylureas was associated with a lower risk of incident Parkinson’s disease.