Metformin Linked To Reduced Risk of Glaucoma

Julia E. Richards, Ph.D. Harold F. Falls Professor of Ophthalmology and Visual Sciences Professor of Epidemiology Director, Glaucoma Research Center The University of Interview with:
Julia E. Richards, Ph.D.

Harold F. Falls Professor of Ophthalmology and Visual Sciences
Professor of Epidemiology
Director, Glaucoma Research Center
The University of Michigan

Medical Research: What is the background for this study?

Response: We have a special interest in how the developmental processes of aging increase the risk of late onset diseases. We wondered whether drugs that target known aging pathways might be able to reduce risk of late onset disease. In the aging field, an emerging area of interest has been the category of drugs called caloric restriction mimetic (CRM) drugs, which have been found to extend life span and to reduce risk or delay onset of some late-onset diseases. These caloric restriction mimetic drugs target a set of pathways that have come to be seen as playing roles in longevity. One of these caloric restriction mimetic drugs, metformin, happens to also be one of the most common drugs used in the treatment of type 2 diabetes.

Glaucoma is a leading cause of blindness worldwide and classical open-angle glaucoma shows onset in late middle age or late age, so we hypothesized that a caloric restriction mimetic drug might be able to reduce the risk of open-angle glaucoma. We used data from a large health services database to compare the rate at which open-angle glaucoma developed in individuals with diabetes mellitus who used metformin versus those who did not use metformin. We predicted that metformin would be associated with reduced risk of open-angle glaucoma.

Medical Research: What are the main findings?

Response: We found that use of metformin was associated with reduced risk of open-angle glaucoma. A 2 gram per day dose of the CRM drug metformin for two years was associated with a 20.8% reduction in risk of developing open-angle glaucoma. When we looked at the highest quartile of drug prescribed (>1,100 grams over a two year period) we found a 25% reduction in risk relative to those taking no metformin. This risk reduction is seen even when we account for glycemic control in the form of glycated hemoglobin, and use of other diabetes drugs was not associated with reduced risk of open-angle glaucoma. A possible explanation for our findings might be that the mechanism of risk reduction is taking place by CRM drug mechanisms that target aging pathways rather than through glycemic control of diabetes.

In the long run, the approaches to late onset diseases in general will become much more powerful if we can use parallel approaches that simultaneously target both the aging processes going on and the disease-specific pathways going on. In the literature we see caloric restriction mimetic drugs metformin, rapamycin and resveratrol all being explored for their ability to target points in aging pathways in ways that can impact the risk of a variety of late-onset diseases, so it will be important for those interested in the risk factors affecting late onset diseases to pay attention to how caloric restriction mimetic drugs might be altering risk for those late onset diseases.

Medical Research: What should clinicians and patients take away from your report?

Response: Our study shows that use of metformin is associated with reduced risk of open-angle glaucoma and that keeping really good control of blood glucose levels is associated with reduced risk of open-angle glaucoma.  But before recommending changes to clinical practice, it would be helpful to perform prospective studies (like a Randomized Clinical trial) to confirm the findings of the present study. This is important because metformin is not without side effects and we would want to be sure that any beneficial effects of using metformin (or higher strengths of metformin) for glaucoma outweigh side effects of this medication. We also need to understand whether metformin protects against glaucoma among persons without diabetes and whether there are subsets of patients who respond better or worse to metformin.

One of the implications of this study is not a new idea with this study, but one that lots of people may not have heard, which is the idea that this general category of drugs, the caloric restriction mimetic drugs, may have the potential to reduce the risk of other late onset diseases, too. If you go look in the literature you will see that rapamycin, resveratrol, and metformin are all associated with reduced risk of a variety of later onset diseases, and there are lots of other late onset diseases that have not been looked at yet.

Medical Research: What recommendations do you have for future research as a result of this study?

Response: Because this is not a clinical trial, and because this study was limited to a very specific population of persons with diabetes who do not yet have glaucoma, there are limitations to the conclusions we can draw concerning clinical care. Because this study involved a health services database, it lacked some types of key information we would normally want to track in a glaucoma study such as information on visual fields or cup to disc ratio that might allow us to investigate progression among those who already have glaucoma, so additional studies are needed to understand what effects metformin has on individuals who already have open-angle glaucoma and to understand how metformin impacts specific glaucoma risk factors such as intraocular pressure. This study points towards the need for the next stage of studies to find out whether these findings could apply to persons who do not have diabetes, and to find out whether metformin might be able to affect progression of glaucoma in those who already have the disease.


Lin H, Stein JD, Nan B, et al. Association of Geroprotective Effects of Metformin and Risk of Open-Angle Glaucoma in Persons With Diabetes Mellitus. JAMA Ophthalmol. Published online May 28, 2015. doi:10.1001/jamaophthalmol.2015.1440.

[wysija_form id=”3″] Interview with: Julia E. Richards, Ph.D., Harold F. Falls Professor of Ophthalmology and Visual Sciences, Professor of Epidemiology, Director, Glaucoma Research Center, The University of Michigan (2015). Metformin Linked To Reduced Risk of Glaucoma 

Last Updated on June 6, 2015 by Marie Benz MD FAAD