Metformin May Lower Odds of Primary Open-Angle Glaucoma in Patients with Diabetes

Sally L Baxter, MD

Credit: Shiley Eye Institute

A new analysis suggests that metformin may reduce the risk of developing primary open-angle glaucoma (POAG) beyond glycemic control.¹

The results, presented at the 83rd Scientific Sessions of the American Diabetes Association (ADA 2023), showed metformin continued to be associated with decreased risk of POAG, when adjusted for factors including HbA1c, while other diabetic medications were associated with an increased risk.

“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,” wrote the investigative team, led by Sally L Baxter, MD, an assistant professor of ophthalmology and biomedical informatics at the Shiley Eye Institute, University of California San Diego.

Glaucoma remains a leading cause of irreversible blindness worldwide; POAG has an estimated global prevalence of 2.4% among adults aged ≥40 years.² Currently, lowering intraocular pressure (IOP) is the primary therapeutic goal, but it may not completely decrease the risk of glaucoma, as POAG can occur with or without increased IOP. Metformin, on the other hand, is one of the safest and most effective antihyperglycemic agents in diabetes management, showing positive effects in weight control, cardiovascular health, and neuroprotection.

Investigators indicate 2 previous clinical trials showed metformin use is associated with reduction in the risk of developing glaucoma, while other studies have indicated metformin may not a play a role in glaucoma.¹ The objective of the current analysis was to investigate the association between metformin use and the incidence of POAG in a large, diverse population using data from the nationwide All of Us Research Program.

The retrospective cohort study included 18,440 participants from the All of Us Research Program, aged ≥40 years, with a diagnosis of diabetes mellitus and without a diagnosis of POAG prior to diabetes diagnosis of metformin use. Upon analysis, investigators found 240 participants received a diagnosis of POAG during all available follow-up time, while 18,200 did not.

In regression-based bivariate analysis, data showed metformin use was significantly associated with lower odds of developing POAG (OR, 0.32; P <.001). Meanwhile, in multivariable regression analysis, metformin also remained protective against POAG (OR, 0.33; P <.001). However, the use of other diabetic medications was associated with an increased odds of developing POAG (OR, 2.06; P = .002).

Moreover, in survival analysis, investigators found the probability of developing POAG was significantly lower for the participants using metformin that for the participants not using metformin (P <.001). The team suggested the study’s findings provide additional large-scale, observational health data supporting the role of metformin in mediating POAG risk.

The investigative team suggested additional research will be necessary, including prospective studies and clinical trials with non-diabetic populations, in order to validate the findings.

“As the standard of care for diabetes medication evolves, it is critical that we understand how different antihyperglycemic agents impact the risk of concomitant chronic diseases, such as POAG,” the study team wrote.

References

1. Sidhu S, Saseendrakumar BR, Wu J, Nudleman EL, Do J, Moghimi SM, Weinreb R, Baxter SL. Association of Metformin Use with Primary Open-Angle Glaucoma Among Patients with Diabetes Mellitus Using Data from the National Institutes of Health All of Us Program. Poster presentation at the 83rd Scientific Sessions of the American Diabetes Association. June 23 – 26, 2023.
2. Zhang, N., Wang, J., Li, Y. et al. Prevalence of primary open angle glaucoma in the last 20 years: a meta-analysis and systematic review. Sci Rep 11, 13762 (2021). https://doi.org/10.1038/s41598-021-92971-w