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Study: Long-term metformin use not linked with AMD risk


The researchers reported that there was no significant difference in the AMD prevalence among the 3 study groups.

A multicenter US study1 revealed that the long-term use of metformin to treat diabetes and lifestyle changes in patients with diabetes were not associated with the risk of age-related macular degeneration (AMD), according to Amitha Domalpally, MD, PhD, from the

Wisconsin Reading Center, Department of Ophthalmology, University of Wisconsin School of Medicine and Public and Health, Madison.

No treatment is currently available for the early stages of AMD, but some retrospective studies2-4 have reported an association between metformin and reduced risk of AMD, the authors explained.

In this follow-up study of the Diabetes Prevention Program,2,5 the Diabetes Prevention Program Outcomes Study (DPPOS), retinal photographs of 1,592 patients with diabetes were evaluated 16 years after a randomized clinical trial that investigated diabetes prevention. The study included 549 patients treated with metformin, 514 undergoing lifestyle intervention to prevent diabetes, and 512 control patients in the placebo arm.

The main outcome measure was the prevalence of AMD in the treatment arms.

AMD findings

The researchers reported that there was no significant difference in the AMD prevalence among the 3 study groups, specifically, 152 (29.6%) in the lifestyle arm, 165 (30.2%) in the metformin arm, and 162 (30.7%) in the placebo arm.

They also reported “no differences in the distribution of early, intermediate, and advanced AMD between the intervention groups.” The mean duration of metformin use was similar for those with and without AMD (mean 8.0 vs 8.5 years, respectively; p =0 .69). The multivariate analysis indicated that a history of smoking was associated with increased risk of development of AMD (odds ratio, 1.30; 95% confidence interval, 1.05-1.61; p =0 .02).

The investigators conclude there was no link between metformin use and prevalence of AMD.

“There was also no association with stages of AMD classified from multimodal imaging, nor was there an association with the duration of metformin use,” they added. “Until randomized data are available, the DPPOS provides strong evidence that does not support the use of metformin in the treatment of any stage of AMD.”


1. Domalpally A, Whittier SA, Pan Q, et al. for the Diabetes Prevention Program Research (DPPOS) Group.Association of metformin with the development of age-related macular degeneration. JAMA Ophthalmol. Published online December 22, 2022. doi:10.1001/jamaophthalmol.2022.5567

2. Brown EE, Ball JD, Chen Z, Khurshid GS, et al. The common antidiabetic drug metformin reduces odds of developing age-related macular degeneration.Invest Ophthalmol Vis Sci. 2019;60:1470-1477. doi:10.1167/iovs.18-26422

3. 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

4. Stewart JM, Lamy R, Wu F, Keenan JD. Relationship between oral metformin use and age-related macular degeneration. Ophthalmol Retina. 2020;4(11):1118-1119. doi:10.1016/j.oret.2020.06.003

5. The Diabetes Prevention Program. The Diabetes Prevention Program: design and methods for a clinical trial in the prevention of type 2 diabetes. Diabetes Care. 1999;22:623-634. doi:10.2337/diacare.22.4.623

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