Diabetes drug could reduce the risk of open-angle glaucoma

Take home:

Use of metformin, a drug therapy for the treatment of diabetes, was found to be associated with reduced risk of adult-onset, open-angle glaucoma in a recent study.

By Vanessa Caceres; Reviewed by Julia E. Richards, PhD

Ann Arbor, MI-A drug used for patients with diabetes could one day become an additional therapy to reduce the risk of open-angle glaucoma.

Researchers tested this hypothesis by analyzing 10 years (2001 to 2010) of longitudinal data from a large U.S. health claims database, according to Julia E. Richards, PhD.

They monitored patients above the age of 40 years with diabetes and who had no pre-existing OAG. They also determine whether the patients used the medication metformin.

The study fits into the broader area of aging research and the use of caloric restriction medications, according to Dr. Richards, Harold F. Falls Professor of Ophthalmology and Visual Sciences, professor of epidemiology, and director of the Glaucoma Research Center, University of Michigan, Ann Arbor, MI.

“It has long been known that caloric restriction through use of a reduced-calorie diet can extend lifespan,” she said. “Further exploration of this topic has shown that there are medications called caloric restriction-mimetic medications; because they imitate or mimic effects of calorie restriction, they can also extend lifespan. Metformin is one of these caloric mimetic medications.”

Other studies have shown how these kinds of medications are associated with reduced risk for later-onset diseases, like some cancers, diabetes, and cardiovascular diseases, according to Dr. Richards.

“Because primary open-angle glaucoma is a late-onset disease, we hypothesized that a caloric restriction mimetic drug might be able to reduce the risk of glaucoma and that the risk reduction might involve action through one or more of these same aging pathways,” she explained.

Research results

Researchers tested the effect of metformin on the risk of developing OAG, adjusting for sociodemographic factors, glycemic control via HbA1c levels, other diabetes medications, and other ocular and systemic conditions.

Of the 150,016 diabetics included in the study, 3.9% developed incident OAG. However, use of more than 1,110 cumulative grams of metformin over two years was associated with a 25% reduction in relative risk of developing OAG compared with no metformin use.

“Every 1 gram increase in metformin was associated with a 0.01% reduced hazard of developing OAG,” the researchers reported.

“For example,” they said, “a person receiving a 2-gram daily dose of metformin-considered a normal dose-over 2 years would show a 13% reduction in absolute risk of OAG relative to someone who did not use the medication.”

Even when researchers took into account HbA1c levels to monitor blood glucose, the reduction in risk still occurred.

“Also, the other medications used to control diabetes were not associated with reduced risk of OAG,” Dr. Richards said.

Mechanism of action

Dr. Richards suggested that this finding might shed light on the mechanism by which glaucoma risk is reduced.

“Metformin may be acting through one of the caloric restriction-mimetic mechanisms, such as pathways involving inflammation, neurogenesis, or one of the aging pathways,” she said.

“It’s not clear yet if the same findings apply to other types of glaucoma, although that would be useful to know for future research,” Dr. Richards said.

It’s also not yet known if metformin can be used to reduce the risk of OAG in non-diabetic patients, she added.

Future work done by Dr. Richards and fellow researchers may explore how metformin affects the risk of glaucoma development in other forms of glaucoma. They also will explore which tissues in the eye change gene expression in response to metformin and investigate whether metformin can reduce the risk of other age-related eye diseases.

Ultimately, metformin could be added the armamentarium for glaucoma treatment, she noted.

“Eventually, the already FDA-approved metformin medication might become available as an additional therapeutic approach to glaucoma,” Dr. Richards said.

Julia E. Richards, PhD

E: richj@umich.edu

This article was adapted from Dr. Richard’s presentation at the 2014 meeting of the Association for Research in Vision and Ophthalmology. Dr. Richards did not indicate any proprietary interest in the subject matter.