Antidiabetic drugs may exert effects beyond glycaemic control and could influence neurodegenerative risk, with sodium-glucose co-transporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1 RA) being associated with lower risk of Parkinson’s disease (PD), suggesting potential neuroprotective effects, a Bayesian network meta-analysis has found.
The meta-analysis included nine observational cohort studies with a total of 712,287 patients. Of the nine studies, one was multinational, three were conducted in the US, two in China, and one each in Norway, Taiwan, and the UK. Seven antidiabetic regimens were included: α-glucosidase inhibitor (AGI), dipeptidyl-peptidase-4 inhibitors (DPP4i), GLP-1 RA, metformin, SGLT2i, sulfonylurea, and thiazolidinediones. Four studies included diabetic patients aged ≥40 years, three of which specifically focused on older patients aged ≥65 years. [J Glob Health 2026;16:04187]
Direct and indirect comparisons across antidiabetic drug classes were synthesized to estimate risk ratios with 95 percent credible intervals, and network geometry was examined using network plots to visualize evidence distribution and network connectivity. The most prevalent comparison pair in the network plot on PD risk across antidiabetic drug classes was DPP4i and SGLT2i.
In the overall analysis, no antidiabetic drug class demonstrated a statistically significant difference in PD risk. Nevertheless, rank probability analyses suggested that GLA-1 RA and SGLT2i were associated with lower PD risk across age, sex and comorbidities.
Subgroup analyses further indicated that SGLT2i tended to be associated with lower PD risk among older adults (≥75 years), women, and those with cardiovascular disease (CVD) history, while GLP-1 RA had a higher probability of lower PD risk in men and patients aged <75 years.
Probability ranking suggested that DPP4i were more likely to be associated with increased PD risk in patients <75 years. In patients with CVD, the risk of PD was higher with metformin vs SGLT2i. In contrast, metformin, sulfonylureas, and AGI were consistently associated with higher ranking probabilities for PD risk compared with newer agents.
Metabolic disorders such as diabetes have been recognized as major contributors to neurodegeneration, whereby systemic metabolic dysregulation accelerates neuronal vulnerability, and consequently increase PD risk. [Parkinsonism Relat Disord 2024;125:107026] As current PD treatments primarily provide symptomatic relief without altering the underlying disease course, identifying modifiable risk factors for PD and developing effective preventive strategies remain crucial.
Recent studies have demonstrated neuroprotective effects of various antidiabetic agents through modulation of neuroinflammation, yet comparative evidence across antidiabetic drug classes remains limited and inconsistent. [J Parkinsons Dis 2024;14:917-924; Front Neurosci 2019;13:868; Brain-X 2024;2:e52; Parkinsonism Relat Disord 2025;130:107220]
According to the authors, the study was the first to evaluate PD risk across multiple antidiabetic drug classes using patient characteristics, and it has provided clinically relevant insights despite study limitations. Further controlled studies to validate these associations and to determine whether antidiabetic therapies can influence PD onset, progression, or long-term neurological outcomes are suggested.