Do oral antidiabetic medications alter the risk of Parkinson’s disease? An updated systematic review and meta-analysis

Background Diabetes mellitus is a known risk factor for Parkinson’s disease (PD), but does this risk vary with antidiabetic medications is still unclear. This meta-analysis aims to compile evidence from the literature to assess the risk of idiopathic PD with various oral antidiabetic medications. Methods Databases PubMed, CENTRAL, Scopus, Web of Science, and Embase were searched till 5th April 2023. Adjusted outcomes were pooled to generate a hazard ratio (HR) on the risk of PD with different antidiabetic medications. Results Fifteen studies with 2,910,405 diabetic patients were eligible. Pooled analysis failed to show any significant difference in the risk of PD among users of metformin (HR: 1.05 95% CI: 0.91, 1.22 I 2 = 81%), glitazones (HR: 0.84 95% CI: 0.68, 1.05 I 2 = 91%), glucagon-like peptide-1 agonists (HR: 0.63 95% CI: 0.26, 1.55 I 2 = 33%), and sulfonylureas (HR: 1.13 95% CI: 0.96, 1.32 I 2 = 76%). However, a meta-analysis of four studies showed that dipeptidyl peptidase-4 inhibitor use was associated with reduced risk of PD in diabetics (HR: 0.69 95% CI: 0.56, 0.86 I 2 = 46%). Insufficient data was available on sodium-glucose cotransporter-2 inhibitors, α-glucosidase inhibitors, and glinides. Conclusions Limited retrospective evidence indicates that DPP4i may reduce the risk of idiopathic PD in diabetics. Metformin, sulfonylureas, glucagon-like peptide-1 agonists, and glitazones were not associated with any change in the risk of PD. Further studies taking into confounding factors and using a common comparator group are needed to strengthen present evidence.