Nancy A. Melville

May 13, 2014

ORLANDO, Florida — Metformin, the popular diabetes drug, is associated with a dose-dependent reduction in risk for open-angle glaucoma, according to new research.

"Should these findings be confirmed in prospective clinical trials, this could lead to novel treatments for this sight-threatening disease and new opportunities to reduce other risks," said lead investigator Julia Richards, MD, from the University of Michigan Kellogg Eye Center in Ann Arbor.

She presented study results here at the Association for Research in Vision and Ophthalmology 2014 Annual Meeting.

Dr. Richards and her colleagues analyzed longitudinal data for 2001 to 2009 from the Clinformatics Data Mart Database, a large health claims database of insured patients in the United States.

They identified 150,016 people 40 years and older with diabetes and no pre-existing open-angle glaucoma, of whom 5893 (3.9%) developed incident open-angle glaucoma.

The risk for open-angle glaucoma was 25% lower in patients with documented cumulative metformin use of more than 1110 g over 2 years (average dose, 2 g/day) than in those with no metformin use (hazard ratio, 0.75; 95% confidence interval, 0.59 - 0.95; P = .017).

The association was dose-dependent, with a 0.01% reduced hazard for open-angle glaucoma with every 1 g increase in metformin (P = .001).

The greatest risk reduction was associated with the highest baseline risk and the highest glycated hemoglobin (HbA1c) levels.

"As we looked at the higher-risk populations with higher HbA1c levels, we found a greater reduction in risk. The people who benefited the least from this were people who were already at low risk and had well-controlled diabetes," Dr. Richards reported.

The findings support the concept that metformin and some other drugs are geroprotective because they produce effects that mimic caloric restriction, Dr. Richards explained.

"The results lead us to believe that our hypothesis has some merit," she said. The metformin could be eliciting a calorie-restriction response in addition to the direct effects on diabetes or glycemic control.

Research into possible mechanisms is looking at how ocular tissue responds to metformin and a host of other questions. "There are a variety of things we don't know at this point," Dr. Richards said.

For example, she explained, "we don't know how our findings relate to uninsured populations, if they apply to nondiabetic individuals, if specific factors like intraocular pressure or age of onset play a role, or if the benefits extend to other types of glaucoma."

The factors potentially contributing to the relation between open-angle glaucoma and diabetes are complex, said session moderator Robert Weinreb, MD, chair, distinguished professor of ophthalmology, and director of the Shiley Eye Center at the University of California, San Diego.

"While some studies have shown that patients with diabetes are more likely to develop open-angle glaucoma, conflicting evidence also exists," said Dr. Weinreb.

"Confounding factors such as level of HbA1c, diabetes duration, renal function, racial differences, genetics, and concomitant systemic disorders and medications all contribute to heterogeneity and variation in theses studies," he told Medscape Medical News.

The constellation of systemic conditions that can affect diabetics, including cardiovascular disorders, high blood pressure, and high blood lipids, can all play a role, Dr. Weinreb added. "For these reasons, it is difficult to draw a conclusion at this time."

"Patients who have these conditions are also likely to use other systemic medications, such as a statin," which could have confounded the study findings, he explained. "To isolate metformin as the single class of medication to affect glaucoma progression is problematic," he said.

Dr. Richards and Dr. Weinreb have disclosed no relevant financial relationships.

Association for Research in Vision and Ophthalmology (ARVO) 2014 Annual Meeting: Abstract 1668. Presented May 5, 2014.

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