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Use of metformin was associated with lower odds of developing age-related macular degeneration (AMD) among patients without a diabetes diagnosis, offering more evidence of a possible role for the inexpensive drug in eye health, according to a case-control study.

After adjusting for risk factors for AMD, use of metformin was associated with reduced odds of any AMD development (adjusted OR 0.83, 95% CI 0.74-0.87), as well as reduced odds of developing dry AMD (aOR 0.85, 95% CI 0.79-0.92), reported Dimitra Skondra, MD, PhD, of the University of Chicago, and colleagues.

They also found a dose-dependent relationship between metformin use and AMD: 2-year cumulative metformin doses of 1 to 270 g, 271 to 600 g, and 601 to 1,080 g were associated with 20%, 19%, and 12% lower odds for developing AMD, respectively, they noted in .

There were similar trends when they focused on dry AMD -- the milder form of the disease versus wet AMD. Compared with no metformin use, 2-year cumulative doses of 1 to 270 g and 271 to 600 g were linked to 18% and 14% lower odds of dry AMD development.

The findings from this study are "very encouraging" and provide support for launching a randomized trial, Skondra told MedPage Today. "We saw a signal in patients who don't have diabetes. If we did show that taking metformin for 4-5 years decreased the risk of more advanced AMD, we could target millions of patients around the world."

She said she initially began exploring a possible role for the diabetes drug after noticing that patients taking it seemed to have less AMD, a leading cause of vision loss for older people.

Several studies have tried to confirm a link, but their findings have been inconsistent. A showed a trend toward less AMD in patients taking metformin, but the difference was not statistically significant. Meanwhile, there's been conflicting research about whether diabetes causes AMD.

For the current study, Skondra and colleagues explored the possible benefits of metformin on AMD development in patients who take metformin for reasons other than diabetes. While not FDA-approved for these purposes, metformin is to treat prediabetes, gestational diabetes, weight gain from antipsychotic medications, and polycystic ovarian syndrome.

Amitha Domalpally, MD, PhD, of the University of Wisconsin-Madison, told MedPage Today that a limitation to this study was the lack of data about possible confounders like diet, body mass index, and smoking.

While she noted that the study was well done, it doesn't prove that metformin prevents AMD. It's possible that patients taking it for reasons other than diabetes -- such as prediabetes and weight control -- were already taking steps to improve their health and therefore lower their risk of AMD.

As for a future prospective randomized trial of metformin in AMD, Domalpally said one would be a good idea, though she added that it would be challenging and expensive because the disease develops slowly.

For her part, Skondra said launching a randomized study will be "a big challenge," since metformin is a cheap medication whose financial prospects may not interest drug companies. "But hopefully we'll find a way forward," she said.

For now, both Skondra and Domalpally said there's not enough evidence to support prescribing metformin to prevent AMD.

For this study, the researchers used insurance claims data from 2006 to 2017 in the Merative MarketScan Research Database for patients without diabetes ages 55 and older and compared 231,142 patients with AMD (mean age 75.1, 60.6% women) against 232,879 matched controls without AMD (mean age 74.9, 57.4% women). The sample also included 144,147 cases with dry AMD that were matched to 144,530 controls. Overall, 1.0% of cases and 1.3% of controls were exposed to metformin in the 2 years before their index visit.

"Notably, the reduced odds of AMD associated with metformin use was also observed in participants taking insulin, sulfonylureas, statins, or glitazones," Skondra's group wrote. "This finding may be due to a true causal association but may also be a result of confounding factors." The other drugs, they added, pose a greater risk for complications than metformin.

The authors also noted that the potential for coding errors in the study was a limitation.

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