Metformin May Protect Against AMD Development in Patients Without Diabetes

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Metformin use was associated with a reduced likelihood of any AMD and dry AMD in a sample of patients without diabetes.

Metformin use was associated with a reduced likelihood of developing any age-related macular degeneration (AMD) among a sample of people without diabetes, according to new results from a case-control study.1

Using data from a nationwide insurance claims database, including ≥231,000 cases with AMD and ≥232,000 matched controls without diabetes, a team of investigators from the University of Chicago observed a non-dose-dependent association between metformin use and 17% lower odds of AMD.

“These results support the hypothesis that metformin may protect against AMD development in patients with diabetes,” wrote the investigative team, led by Dimitra Skondra, MD, PhD, of the department of ophthalmology and visual science at the University of Chicago.

Recent findings have suggested metformin use is associated with protection against AMD development in people with diabetes.2 However, these observational data are often inconsistent and do not necessarily imply a causal relationship, requiring a randomized controlled trial. In particular, study data have not accurately captured the potential protection of metformin among cases of AMD without diabetes.

For trial inclusion, data from 2006 to 2017 in the Merative MarketScan Research Database were used to identify patients aged ≥55 years with newly diagnosed AMD.1 AMD cases and controls were matched 1:1 based on year, age, presence of anemia or hypertension, region, and Charlson Comorbidity Index score. Cases and controls were required to have ≥2 eye examinations 12 months before the index date, defined as the date of AMD diagnosis or a randomly selected eye examination, respectively.

Exposure to metformin in the 2 years before the index date for each study group was compared and categorized into quartiles, based on cumulative treatment doses (1-270, 271-600, 601-1080, and >1080 g/2 y). Multivariable logistic regression was performed to assess the association between metformin use and the odds of developing any AMD, after adjusting for known AMD risk factors, including female sex, hyperlipidemia, smoking, and exposure to other antidiabetic medications.

A total of 231,142 patients without diabetes and any AMD (mean age, 75.1 years; 60.6% female) and 232,879 matched controls without diabetes and AMD (mean age, 74.9 years; 57.4% female) were identified for analysis. The sample also included 144,17 cases with dry AMD matched to 144,530 controls. Overall, 2268 (1.0%) cases and 3087 controls (1.3%) were exposed to metformin within the 2 years before the index visit.

In adjusted analyses, investigators found exposure to any metformin was associated with reduced odds of any AMD development (adjusted odds ratio [aOR], 0.83; 95% CI, 0.74 - 0.87). Compared with no metformin use, 2-year metformin doses of 1 to 270, 271 to 600, and 601 to 1080 g were associated with 20%, 19%, and 12% lower odds of AMD, respectively.

Any use of metformin showed a 15% decrease in the likelihood of developing dry AMD (aOR, 0.87; 95% CI, 0.79 - 0.92). Compared to no metformin use, dosing quartiles of 1 to 270 and 271 to 600 g were associated with 18% and 14% lower odds of developing dry AMD, respectively.

Investigators noted the likelihood of developing AMD did not significantly differ across the dosing quartiles in any AMD or dry AMD samples. After performing Asymptotic Cochran-Armitage tests for the trend, data showed 2-sided P values of P = .51 and P = .66 for any AMD and dry AMD samples, respectively.

Skondra and colleagues noted the odds reductions of AMD associated with metformin were observed in all, but the highest cumulative dose quartile in any AMD group, and the lower 2 quartiles of metformin use in the dry AMD group. As a result, they suggest the benefits of metformin for AMD may not be dose dependent.

“Randomized clinical trials are warranted to help determine if the association between metformin and AMD among patients without diabetes is causal and if the management of AMD should change,” investigators wrote.


  1. Aggarwal S, Moir J, Hyman MJ, et al. Metformin Use and Age-Related Macular Degeneration in Patients Without Diabetes. JAMA Ophthalmol. Published online November 30, 2023. doi:10.1001/jamaophthalmol.2023.5478
  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. doi:10.1001/jamaophthalmol.2020.6331