Association of metformin use with primary open-angle glaucoma using data from the National Institutes of Health All of Us Program.

Background: Few studies have assessed the impact of metformin use on glaucoma risk. The purpose of this study was to examine the association between metformin use and the incidence of primary open-angle glaucoma (POAG) in a diverse and large nationwide cohort.

Methods: We included a retrospective cohort study of 18 440 participants in the National Institutes of Health All of Us Research Program aged 40 years or older, with a diagnosis of diabetes mellitus and without a diagnosis of POAG prior to diabetes diagnosis or metformin use. Bivariate logistic regression, multivariable logistic regression and survival analysis were used to analyse the association between ever use of metformin and incidence of POAG.

Results: Within the cohort, 240 participants acquired a diagnosis of POAG during all available follow-up time, while 18 200 did not. In regression-based bivariate analysis, metformin use was significantly associated with a lower odds of developing POAG (OR 0.35, 95% CI 0.26 to 0.47, p<0.001). In multivariable regression analysis, metformin remained protective against POAG (OR 0.33, 95% CI 0.21 to 0.50, p<0.001), while the use of other diabetic medications was associated with an increased odds of developing POAG (OR 2.39, 95% CI 1.48 to 3.90, p<0.001). In survival analysis, the probability of developing POAG was significantly lower for the participants using metformin than for the participants not using metformin (log-rank p<0.001, Cox proportional HR 0.38, 95% CI 0.29 to 0.51).

Conclusions: This study provides additional large-scale observational health data supporting the protective role of metformin in the development of POAG. However, limitations include the study's observational design and lack of data on metformin dosage and duration, glaucoma severity and ocular exam findings. Despite these limitations, our findings contribute to the growing body of evidence suggesting a potential protective effect of metformin against POAG.