Study Links Metformin to Lower Glaucoma Risk in Nationwide Cohort

A nationwide cohort study of 18,440 adults with diabetes found that those prescribed metformin had significantly lower odds of developing primary open-angle glaucoma. Using up to 20 years of follow-up data from the NIH All of Us program, the study underscores metformin’s potential protective role and the importance of diverse representation in glaucoma research. Photo: Merck. Click image to enlarge. Lowering intraocular pressure (IOP) is of course the current mainstay of treating primary open-angle glaucoma (POAG), which is estimated to affect 68.6 million people over age 40 worldwide. Although IOP is the only modifiable risk factor currently, glaucoma can occur with or without elevated pressure, and lowering IOP doesn’t guarantee a reduced risk of glaucoma in all patients. Other therapeutic modalities are emerging in research, including use of metformin, a medication typically used to manage type 2 diabetes that has been found to have some neuroprotective benefits in the eye. Evidence on its direct impact on glaucoma development is conflicting, yet a new study has released results using a nationwide database, suggesting that patients who took metformin had a lower probability for developing POAG.Researchers conducted a retrospective cohort study of 18,440 participants from the National Institutes of Health All of Us Research Program. Participants were aged 40 years or older with a diagnosis of diabetes and without a diagnosis of POAG prior to diabetes diagnosis or metformin use. Within this cohort, 240 participants subsequently acquired a diagnosis of POAG during all available follow-up time. Of those, the mean age of participants at time of analysis was 71.1 years. Female participants (n=135) comprised 56.3% of the cases, and Black or African-American participants (n=98) represented 40.8%. The majority of the participants who were diagnosed with POAG were not Hispanic or Latino (n=194, 80.8%). Results were published last week in British Medical Journal Open Ophthalmology.Within the cohort of the 18,200 participants who did not develop glaucoma, the mean age was 65.6 years. White participants (n=7,944) represented 43.7% of this cohort, and 76.5% were not Hispanic or Latino (n=13,928). The majority of participants who did not develop POAG had type 2 diabetes (n=17,421, 95.7%) and were prescribed metformin (n=11,185, 61.5%). The study authors found significant differences in the distribution of each of the risk predictors between the two cohorts, including age, gender, ethnicity, annual income, type 1 diabetes, type 2 diabetes and use of metformin. Similarly, in regression-based bivariate analysis, demographic factors such as age, education level and annual income were significantly associated with increased odds of developing POAG, the authors wrote in the journal. “Additionally, use of other diabetes medications was associated with increased POAG incidence,” they continued. “Male gender, ‘other’ race, increased HbA1c and type 2 diabetes remained associated with decreased risk of POAG. Even after adjustment for demographic and medical covariates, use of metformin (OR 0.33) remained associated with decreased odds of developing POAG.”The authors also noted the use of the All of Us database, which includes underrepresented populations. “The racial and ethnic diversity of our study population offers new and deeper insight into the relationship between metformin and POAG,” wrote the authors. “Because people of African-American and Latino ancestry carry a disproportionate burden of glaucoma and glaucoma-related visual impairment, the broader representation reflected in this study uniquely adds to the literature on metformin and glaucoma.” Follow-up data allowed for analyses over a 20-year period, the longest follow-up period of any study on metformin and glaucoma to date, they continued.Although the biological mechanism contributing to metformin’s observed protective effect on POAG development remains unclear, this study adds to the literature that use of other antihyperglycemic agents may potentially be associated with greater POAG risk.Limitations mentioned by the authors include the lack of consistent data on metformin dosage and duration, as well as limited data on glaucoma severity. Finally, they mentioned the observational study design can only establish associative, not causative, relationships.“Overall, our study provides additional large-scale observational health data supporting the potential protective effects of metformin in mediating POAG risk and motivates future investigation. Additional research, namely prospective studies and clinical trials with non-diabetic populations, detailed information regarding metformin dosage and duration, and visual and glaucoma-related end points, is warranted to validate these findings. Given the limited prevention and treatment strategies for glaucoma, validation of the protective effects of metformin on POAG development and progression would represent a major advancement in uncovering new therapeutic modalities for POAG,” concluded the authors.Click here for the journal source. Sidhu S, Saseendrakumar BR, Varkhedi V, Wu J, Parikh A, Nudleman E, et al. Association of metformin use with primary open-angle glaucoma using data from the National Institutes of Health All of Us Program. BMJ Open Ophthalmology. September 12, 2025. [Epub ahead of print.] This article was developed by the editorial staff in conjunction with experts in the field. In the process, AI may have been among the editorial tools used to meet the goals of human editors, who approved all content.