Metformin and Age-related Macular Degeneration

Metformin, classified as biguanide, is the first-line and most widely used medication for patients with type 2 diabetes. In addition to its main effect of inhibiting hepatic glucose production, metformin has also been found to decrease oxidative stress. Furthermore, researchers from the University of Chicago Medical Center reported that a low dose of metformin could reduce the risk of age-related macular degeneration (AMD). The research has been published in the journal JAMA Ophthalmology on January 21, 2020.

Age-related macular degeneration is the leading cause of irreversible blindness in older adults and it appears to have no effective preventive measures. Previous studies have shown that the common antidiabetic drug metformin has protective outcomes in multiple age-associated diseases. However, the effect of metformin against the development of AMD remains unclear. Therefore, Dr. Andrea L. Blitzer and colleagues conducted a study to evaluate whether metformin use is associated with reduced odds of developing AMD.

It was a population-based, case-control study of patients from a nationwide health insurance claims database. Researchers determined participants of 55 years and older with newly diagnosed AMD from January 2008 to December 2017 as cases and matched them with control participants. They identified dosage of metformin and exposure to other prescribed medications using outpatient drug claims. The major outcome assessed was the risk of developing AMD. They included a total of 312,404 participants in the case group and matched them with 312,376 participants in the control group.

Key Findings of the Study

• Upon analysis, researchers noted that the case group had a slightly higher percentage of participants with diabetes (26.0%) compared with the control group (25.5%).
• They found Metformin use was associated with reduced odds of developing AMD (odds ratio [OR], 0.94).
• They mentioned that this association was dose-dependent, with low to moderate doses of metformin showing the greatest potential benefit (dosages over 2 years: 1-270 g, OR, 0.91; 271-600 g, OR, 0.90; 601-1080 g, OR, 0.95).
• However, they found no association with reduced odds of developing AMD at 2 years for doses greater than 1080 g.
• The researchers noted a dose-dependent preservation decrease in the odds of patients developing AMD when looking only at patients with diabetes.
• They also found that the benefit of metformin only occurred in the absence of diabetic retinopathy.

The authors concluded, "In this study, metformin use was associated with reduced odds of developing AMD. This association was dose-dependent, with the greatest benefit at low to moderate doses. When looking only at patients with diabetes, we saw a preservation of the dose-dependent decrease in the odds of patients developing AMD".

They further added, "Metformin does not appear to be protective in patients with diabetes and coexisting diabetic retinopathy. This study suggests that metformin may be useful as a preventive therapy for AMD and provides the basis for potential prospective clinical trials".

For further information: JAMA Ophthalmology