Purpose: To examine the association between metformin use and the incidence of primary open-angle glaucoma (POAG) in a nationwide cohort of patients with diabetes mellitus.

Methods: The National Institutes of Health All of Us Research Program represents a nationwide effort to recruit a diverse participant pool through the inclusion of historically excluded and underrepresented populations. We conducted a retrospective cohort analysis of 18,440 participants in the All of Us database 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 analyze the association between metformin use and incidence of POAG based on electronic health record (EHR) data. In chi-squared and regression modeling, controls were randomly sampled at a 4:1 control: case ratio, resulting in analysis of data from 1,200 participants.

Results: 240 participants acquired a diagnosis of POAG during all available follow-up time, while 18,200 did not. In bivariate analysis, metformin use was significantly associated with a lower odds of developing POAG (odds ratio [OR] 0.32, 95% confidence interval [CI] 0.23-0.42, p<0.001). In multivariable regression analysis, metformin remained protective against POAG (OR 0.33, 95% CI 0.22-0.50, p<0.001), while the use of other diabetic medications was associated with an increased odds of developing POAG (OR 2.06, 95% CI 1.31-3.27, p=0.002). In survival analysis, the probability of developing POAG was significantly lower for participants using metformin than for participants not using metformin (log-rank p<0.001, Cox proportional hazards ratio 0.33, 95% CI 0.25-0.44).

Conclusion: This study provides additional large-scale observational health data supporting the protective role of metformin in the development of POAG.


S. Sidhu: None. B. Radha saseendrakumar: None. J. Wu: None. E. L. Nudleman: Consultant; Roche Pharmaceuticals, EyeBio, Alcon Research, LLC. J. Do: Consultant; Voxelcloud Inc., Other Relationship; Nicox, Research Support; National Eye Institute, Speaker's Bureau; Medical Education Speakers Network. S. M. Moghimi: None. R. Weinreb: Consultant; AbbVie Inc., Alcon, Allergan, Amydis, Equinox, Other Relationship; NIH - National Institutes of Health, Carl Zeiss Meditec, Topcon, Nicox, Novartis, Toromedes, Research Support; Heidelberg. S. L. Baxter: Consultant; voxelcloud, Other Relationship; iVista Medical Education, Research Support; Topcon, Optomed.


University of California San Diego; National Institutes of Health (DP5OD029610, P30EY022589); National Institutes of Health, Office of the Director, Regional Medical Centers (1OT2OD026549, 1OT2OD026554, 1OT2OD026557, 1OT2OD026556, 1OT2OD026550, 1OT2OD026552, 1OT2OD026553, 1OT2OD026548, 1OT2OD026551, 1OT2 OD026555); IAA (AOD16037); Federally Qualified Health Centers (HHSN263201600085U); Data and Research Center (5U2COD023196); Biobank (1U24OD023121); The Participant Center (U24OD023176); Participant Technology Systems Center (1U24OD023163); Communications and Engagement (3OT2OD023205, 3OT2OD023206); Community Partners (1OT2OD025277, 3OT2OD025315, 1OT2OD025337, 1OT2OD025276)

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