AIMS: This study aimed to investigate the association between sodium-glucose cotransporter 2 inhibitors (SGLT2is), glucagon-like peptide-1 receptor agonists (GLP-1RAs), and the risk of Parkinson's disease (PD) in patients with type 2 diabetes (T2D).
METHODS: We conducted a real-world cohort study using the TriNetX U.S. Research Network. Adults aged ≥ 50 years with T2D initiating SGLT2is, GLP-1RAs, or dipeptidyl peptidase-4 inhibitors (DPP4is) between 2015 and 2022 were included. A landmark analysis using a new-user, active-comparator design with propensity score matching was applied. The primary outcome was incident PD. A meta-analysis incorporating additional real-world studies was also performed.
RESULTS: In total, 93,872, 110,366, and 95,838 patients were included in the SGLT2i vs. DPP4i, GLP-1RA vs. DPP4i, and SGLT2i vs. GLP-1RA comparisons, respectively. SGLT2i users had a significantly lower risk of PD compared with both DPP4i users (HR = 0.80, 95 % CI: 0.69-0.93, p = 0.003) and GLP-1RA users (HR = 0.80, 95 % CI: 0.69-0.93, p = 0.003). No significant difference was observed between GLP-1RA and DPP4i users (HR = 0.97, 95 % CI: 0.85-1.10, p = 0.656). The meta-analysis further supported the reduced PD risk associated with SGLT2i use.
CONCLUSIONS: SGLT2i use was associated with a significantly lower risk of PD compared with both DPP4i and GLP-1RA use in patients with T2D.
