Association between metformin and neurodegenerative diseases of observational studies: systematic review and meta-analysis

BACKGROUND AND AIMS: Aging becomes a growing global concern with an increased risk of neurodegenerative diseases (NDs) that mainly consist of cognitive decline and Parkinson disease (PD). As the most commonly prescribed antidiabetic drug, metformin has been shown to have inconsistent roles in the incidence of NDs. We performed a systematic review and meta-analysis of observational studies to evaluate the effect of metformin exposure on onset of NDs. METHODS: The observational studies that investigated the associations between metformin and the incidence of NDs were searched in MEDLINE, Embase and Cochrane Library databases. A random-effect model was performed using STATA to calculate the combined ORs. RESULTS: In total, 23 comparisons out of 19 studies with 285 966 participants were included. Meta-analysis found there was no significant effect on incidence of all the subtypes of NDs with metformin exposure (OR 1.04, 95% CI 0.92 to 1.17). However, metformin monotherapy was associated with a significantly increased risk of PD incidence compared with non-metformin users or glitazone users (OR 1.66, 95% CI 1.14 to 2.42). CONCLUSION: Metformin has failed to demonstrate a beneficial effect on NDs. In addition, it may increase the risk of PD development. In light of current results, how metformin would impact NDs, especially the potential risk of PD, needs to be scrutinized. The underlying mechanisms are vital to achieve some more profound understanding on the regimen. TRIAL REGISTRATION NUMBER: CRD 42019133285.