Diabetes Drug Metformin Associated with Reduced AMD Risk

Patients who take metformin, a diabetes drug, may experience a protective effect against developing age-related macular degeneration (AMD), according to a new report. In a case-controlled study, metformin use was associated with 58% reduced risk of developing AMD (odds ratio, 0.58; 95% confidence interval, 0.43-0.79).

Investigators from the University of Florida conducted a retrospective case-controlled study examining whether metformin use was associated with decreased risk of developing AMD. The investigators pulled medical records from University of Florida health clinic patients older than 55 years and matched every AMD case with 3 controls.

The study authors noted that some previously-published literature suggests metformin can reduce the risk for developing several ocular diseases, but none had looked at AMD specifically.

There were 1947 patients who visited these clinics between June 2011 and June 2017 that had AMD who were then matched with 5841 controls. Further classification determined 505 patients had dry AMD (geographic atrophy) and 115 patients had wet (neovascular) AMD; the study authors said it was not possible to determine the type of AMD for the remaining patients.

Among control patients, 10.44% had a history of metformin use while just 4.37% of the AMD patients had a history of taking metformin, the study authors determined.

There were significantly decreased odds of developing AMD among metformin users, the investigators learned. This was true when they used both univariate analysis and conditional multivariable logistic regression, they said.

The investigators wanted to ensure that the protective effect was in fact stemming from metformin, so they examined the use of other common drugs including dipeptidyl peptidase 4 (DPP4) inhibitors, selective serotonin reuptake inhibitors (SSRI), tetracyclic antidepressants, and statins. Many of the patients in their analysis were prescribed these drugs, but none of them were linked to the reduced odds of developing AMD. In fact, some of them were associated with increased odds.

Diabetes itself was associated with a statistically significant decreased risk for developing AMD, the investigators found. They believe that the effect of metformin use is independent of a diabetes diagnosis.

A subgroup analysis of this cohort showed that metformin use was associated with decreased odds of developing AMD among patients who had both AMD and diabetes. There were 837 patients who had both, and of those, 84 patients were taking metformin.

“We found that metformin, but not other medications, was associated with decreased odds of developing AMD,” the study authors concluded. “These findings suggest that metformin itself, and not other medications, has an important protective role.”

While neither metformin dosage nor length of time prescribed metformin were taken into account for this analysis of AMD risk, the study authors found cited previous literature that suggested every cumulative increase of metformin dose by 1 g showed a 0.16% reduction in the odds of developing open angle glaucoma. That study further showed the highest metformin usage group experienced the highest reduction odds.

“This is a retrospective study and a causal relationship cannot be established; future work using directed acyclic graphs may assist in elucidating the causal pathways,” the study authors wrote, adding that a phase 2, single-blind, randomized clinical trial is underway to examine the safety and efficacy of metformin use to decrease geographic atrophy progression in a small group of nondiabetic patients with dry AMD. “Future prospective studies should further investigate the protective effect of metformin on AMD in large-scale multicenter clinical trials.”

The paper, “Common Antidiabetic Drug Metformin Reduces Odds of Developing Age-Related Macular Degeneration,” was published in Clinical and Epidemiologic Research.