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Aims
The association between metformin use and neurodegenerative disease (ND) onset remains controversial. In this systematic review and meta‐analysis, we aimed to determine the relationship between metformin use and ND risk based on data from population‐based cohort studies.
Methods
Articles were systematically searched in PubMed, EMBASE and Cochrane Library databases. Pooled relative risks (RRs) with 95% CIs were obtained using a random‐effects model. Subgroup analyses, sensitivity analyses and meta‐regression were performed to identify the sources of heterogeneity and strengthen the results.
Results
Twelve population‐based cohort studies involving 194,792 participants (94,462 metformin users and 100,330 metformin non‐users) were eligible for inclusion in this meta‐analysis. The pooled RR of NDs reached 0.77 (95% CI 0.67–0.88) when comparing metformin users with non‐users. The effects were more prominent in long‐term metformin users (≥4 years) (RR 0.29, 95% CI 0.13–0.44) and studies from Asian countries (RR 0.69, 95% CI 0.64–0.74). The effect estimates were stable when stratified by subtypes of NDs, study designs, and control definitions (p for interaction >0.05). Meta‐regression did not identify the coefficients as the sources of heterogeneity (all p > 0.05).
Conclusions
This systematic review and meta‐analysis found that metformin use, especially long‐term use, was associated with lower ND risk. However, because there was substantial heterogeneity among studies, high‐quality randomized controlled trials are still needed to confirm this finding.