Metformin’s effects may be independent of insulin’s potential effects. In the subgroup analysis of diabetic patients who weren’t exposed to insulin, metformin remained protective. Photo: McGuff Medical. Click image to enlarge.
A common oral diabetic medication may provide some measure of protection against the pathogenesis of age-related macular degeneration (AMD), according to a study recently published in Retina. Metformin has demonstrated anti-angiogenic, anti-inflammatory and antioxidant effects in the retina. Researchers looked at AMD subtypes and investigated the association of metformin use with new onset neovascular AMD (nAMD). They found that the drug reduced the odds of developing this condition.
The case-control study included 86,930 subjects newly diagnosed with nAMD and 86,918 matched controls, as well as a subgroup analysis of 22,117 diabetic subjects and 21,616 diabetic controls. The researchers calculated the risk of various exposures on nAMD development.
Overall, they reported that metformin use was associated with a reduced odds ratio of developing nAMD (OR 0.95) in both cohorts, but especially in those without diabetic retinopathy (DR). They noted that this association with reduced odds remained after Bonferroni correction, which is interesting since previous studies reported that insulin and meglitinides also reduced the odds of nAMD in multivariable analyses but weren’t significant after Bonferroni correction.
In the diabetic cohort without DR, the researchers observed reduced odds of nAMD development at 24-month cumulative doses of 1 to 300 g, 301 to 630 g and 631 to 1,080 g.
They hypothesized in their paper that the dose ceiling effect they saw in subjects without DR may indicate that metformin is more effective in those with greater glycemic control, since these patients didn’t require the maximum dose and may have had less baseline pathologic retinal stress. In these patients, they wrote that it’s possible that metformin can reduce retinal stress to levels that prevent nAMD development. For patients who already have DR, the researchers believe that their baseline retinal stress levels may be too severe for metformin to have any effect within the study window.
“As there are only costly therapeutics in the. Market and limited preventive treatments, further investigation is warranted to validate and expand on these findings and understand how metformin may be repurposed as an additional therapeutic intervention to prevent this blinding disease,” the researchers concluded in their paper.
Khanna S, Shaw L, Hyman MJ, et al. Association of metformin use with risk of newly onset neovascular age-related macular degeneration development. Retina 2023. [Epub ahead of print].