1. In a systematic review and meta-analysis of observational studies on patients with diabetes, metformin use was associated with a significant 19% decrease in odds of age-related macular degeneration (AMD).
2. Analysis by racial and ethnic subgroups showed that metformin was associated with significantly decreased odds of AMD in Black and Hispanic, but not White or Asian, populations.
Evidence Rating Level: 2 (Good)
Study Rundown: Age-related macular degeneration (AMD) is the most common cause of blindness in elderly Americans. The pathophysiology of AMD is incompletely understood, but involves oxidative stress and inflammation. Metformin has been identified as a potential agent to prevent or treat AMD, but studies have shown mixed results. This study aimed to use a systematic review and meta-analysis to assess the existing evidence on metformin in preventing AMD in patients with diabetes mellitus. Among nine observational studies including nearly 1.5 million subjects, use of metformin was significantly associated with 19% decreased odds of AMD, though with high heterogeneity between the pooled odds ratios. The effect of metformin on the odds of AMD was statistically significant in Black and Hispanic populations, but not in White or Asian populations. Stratification by AMD type (“dry” versus “wet,” or neovascular AMD) revealed no significant difference associated with metformin use in either group. Interpretation is limited by heterogeneity between included studies as well as the fact that the analysis did not include metformin dosage, but this meta-analysis supports a role for metformin in preventing AMD. Metformin, of course, has other proven benefits in the studied population, patients with diabetes. However, this study provides further impetus and direction for study of AMD pathogenesis and potential use of metformin and similar agents in other populations.
In-Depth [systematic review and meta-analysis]: Observational studies, including cross-sectional, cohort, and case-control studies, comparing use of oral metformin to a control group not using metformin were included. All subjects had type 1 and/or type 2 diabetes mellitus with no preceding diagnosis of AMD. Among the nine included studies, four had high risk of bias based on the Risk of Bias in Non-randomized Studies of Exposure tool due to non-adjustment for smoking history. A sensitivity analysis excluding these studies did not meaningfully change the results from the primary analysis. Trial sequential analysis was performed and indicated that the required information size was exceeded. The pooled odds ratio of 0.81 for metformin use on AMD risk had a 95% confidence interval (CI) of 0.70 to 0.93 (p<0.01) and an I2 statistic of 96%. The pooled odds ratios for metformin use in Black populations was 0.61 (95% CI 0.58-0.64) and in Hispanic population was 0.85 (0.81-0.89). In a subgroup analysis by study design, metformin use remained significantly associated with lower AMD risk in cohort studies but not in other study designs.
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