Association between oral metformin use and the risk of age-related macular degeneration: A systematic review with meta-analysis

Rodent studies demonstrate that oral metformin use may reduce chronic low-grade inflammation, downregulate apoptosis and extend life span. Emerging epidemiological evidence suggests that oral metformin use may protect against development of age-related macular degeneration (AMD) in humans. In this study, we systematically reviewed the literature on the association between oral metformin use and AMD in patients with type 2 diabetes and conducted a quantitative meta-analysis to provide a summary estimate of the association. We searched 12 literature databases on 10 August 2022 and identified nine eligible studies with data on a total of 1 427 074 individuals with diabetes. We found that patients with diabetes using metformin had a significantly lower odds ratio (OR) of having or developing AMD (OR 0.63; 95% CI: 0.46-0.86; p = 0.004). Our analyses also revealed that although the findings were robust in the sensitivity analysis, the Funnel plot indicated a certain publication bias towards finding a protective effect. Results of individual studies suggested inconsistent findings, as some studies found lower risk of AMD from higher total metformin exposure, whereas other studies found a higher risk of AMD from higher total metformin exposure. Taken together, there may be a link between metformin use and lower risk of AMD, but the relationship is only studied in observational studies, various sources of bias can be speculated to influence, and careful interpretation is warranted.