Metformin Use Associated With Decreased Odds of Dry Age-Related Macular Degeneration

Dimitra Skondra, MD, PhD

Credit: University of Chicago

New findings from a recent case–control study conducted at The University of Chicago suggests the use of metformin was associated with decreased odds of developing new-onset dry age-related macular degeneration (AMD).¹

After analyzing nearly 200,000 AMD cases and their matched controls, the investigative team observed a protective effect for cumulative 2-year doses of metformin below 601 g and a persistent association for patients with diabetes, particularly those without diabetic retinopathy.

“Ultimately, these data suggest a potential role for metformin in preventing dry AMD, and follow-up studies should expand on this work by analyzing the association between metformin use and the progression of dry AMD, specifically to advanced dry AMD or geographic atrophy,” wrote the investigative team, led by Dimitra Skondra, MD, PhD.

The prevalence of AMD is expected to grow alongside the rapidly aging global population, particularly dry, or non-neovascular AMD, which marks 85% of the current disease burden. As there are limited interventions for dry AMD, there is a greater unmet need for both safe and non-invasive strategies to prevent or slow its growth. Evidence suggests metformin has anti-angiogenic, anti-inflammatory, and neuroprotective effects in the retina, suggesting its potential to slow the progression of AMD.

A previous report from the investigative team reported any metformin use was associated with decreased odds of developing new-onset AMD of any subtype (odds ratio [OR], 0.94; 95% CI, 0.92 - 0.96).² However, despite the evidence, there are less conclusive results on the association between metformin use and the development of dry AMD.

Investigators performed a large, national case-control study to investigate this association, examining 194,135 cases with diagnoses of new onset of any subtype between January 2008 - December 2017 in the Metative MarketScan Commercial and Medicare databases.¹ Each case was matched to a control, for a total of 193,990 matched controls.

Multivariable conditional logistic regression was used to assess the association between the development of dry AMD and metformin use. It was additionally used to analyze the association between the development of dry AMD and 2-year cumulative doses of metformin, categorized by quartile: 1 to 270 g, 271 to 600 g, 601 to 1080 g, and >1080 g. Investigators repeated the multivariable logistic regression in a subset of patients with dry AMD and matched controls with diabetes (cases, n = 49,988; controls, n = 49,460).

After performing multivariable conditional logistic regression, any metformin use was associated with decreased odds of developing dry AMD (OR, 0.97; 95% CI, 0.95 - 0.99). The protective effect remained for the cumulative 2-year doses of metformin of 1 to 270 g (OR, 0.93; 95% CI, 0.90 - 0.97) and 271 to 600 g (OR, 0.92; 95% CI, 0.89 - 0.96).

Within the diabetic subgroup, the 2-year cumulative doses of 1 to 270 g and 271 to 600 g decreased the odds of developing dry AMD (1–270 g: OR, 0.95 [95% CI, 0.91 - 0.99]; 271 - 600 g: OR, 0.92 [95% CI, 0.89 - 0.96]). The analysis showed the odds of developing dry AMD were not affected by any metformin use in people with diabetes with diabetic retinopathy.

However, in people with diabetes without diabetic retinopathy, investigators found the odds of dry AMD decreased for any metformin use (OR, 0.97; 95% CI, 0.94 - 0.998) and cumulative 2-year doses of 1 to 270 g (OR, 0.96; 95% CI, 0.91 - 0.998) and 271 to 600 g (OR, 0.92; 95% CI, 0.88 - 0.96). Skondra and colleagues noted the association between metformin use and decreased odds of dry AMD will need to be validated further for conclusive evidence.

“To definitively determine the efficacy of metformin in preventing dry AMD, metformin would have to be evaluated in patients without diabetes in a prospective clinical trial,” investigators wrote.

References

1. Kaufmann GT, Hyman MJ, Gonnah R, Hariprasad S, Skondra D. Association of Metformin and Other Diabetes Medication Use and the Development of New-Onset Dry Age-Related Macular Degeneration: A Case-Control Study. Invest Ophthalmol Vis Sci. 2023;64(11):22. doi:10.1167/iovs.64.11.22
2. Blitzer AL, Ham SA, Colby KA, Skondra D. Association of metformin use with age-related macular degeneration: a case–control study. JAMA Ophthalmol. 2021;139(3):302– 309.