Soo Hyeon Lee, Yujin Rho, Sangyoon Lee, Sooyoung Shin, Yeo Jin Choi
Our analysis suggests that antidiabetic drugs may exert effects beyond glycaemic control and could influence neurodegenerative risk. Furthermore, SGLT2i and GLP-1RA were consistently associated with lower PD risk, suggesting potential neuroprotective effects. While our results indicate the potential importance of antidiabetic drug selection in patients at risk for neurodegenerative diseases, further large-scale, controlled studies should validate these associations and clarify potential mechanisms.
BACKGROUND: Diabetes mellitus is recognised as a risk factor for Parkinson's disease (PD); however, comparative evidence regarding PD risk across antidiabetic drug classes remains limited and inconsistent. We aimed to compare the risk of PD across different antidiabetic classes, with stratified analyses by age, sex, and cardiovascular disease (CVD) status.
METHODS: We searched the Cochrane Library, Embase, and PubMed until August 2025 for studies assessing the association between antidiabetic drugs and PD incidence. We performed a Bayesian network meta-analysis, estimating effect sizes as risk ratios with 95% credible intervals. We performed prespecified subgroup analyses according to age, sex, and CVD status.
RESULTS: We included nine observational cohort studies, totalling 712 287 patients. No antidiabetic class demonstrated a statistically significant difference in PD risk. Rank probability analyses suggested that sodium-glucose co-transporter-2 inhibitors (SGLT2i) tended to rank lowest in PD risk among older adults (≥75 years), while glucagon-like peptide-1 receptor agonist (GLP-1RA) ranked lowest in patients aged <75 years. In patients with CVD, metformin showed relatively higher-ranking probabilities for PD risk compared with SGLT2i. In contrast, metformin, sulfonylureas, and α-glucosidase inhibitors were consistently associated with higher ranking probabilities for PD risk compared to newer agents.
CONCLUSIONS: Our analysis suggests that antidiabetic drugs may exert effects beyond glycaemic control and could influence neurodegenerative risk. Furthermore, SGLT2i and GLP-1RA were consistently associated with lower PD risk, suggesting potential neuroprotective effects. While our results indicate the potential importance of antidiabetic drug selection in patients at risk for neurodegenerative diseases, further large-scale, controlled studies should validate these associations and clarify potential mechanisms.
REGISTRATION: PROSPERO: CRD420251130232.