Doctors are finding new hope for people at risk of losing their sight from age-related macular degeneration, or AMD. Research from the University of Liverpool suggests that metformin, a long-used diabetes drug, may slow the disease before it reaches more serious stages.
Metformin was approved by the U.S. Food and Drug Administration (FDA) in 1994 for the treatment of type 2 diabetes. It was earlier approved for use in the UK in 1958.
AMD primarily affects the area of the retina responsible for sharp vision, known as the macula, and damages the light-sensitive cells that comprise that part of the retina over time. As a result, people develop difficulty reading, driving, and recognizing faces. It is also the leading cause of blindness in high-income countries.
This new research focuses on finding ways to protect individuals with diabetes and over the age of 55 from developing intermediate stages of AMD as they age. After five years, those who were taking metformin were approximately 67% less likely than those not taking metformin to have developed intermediate AMD.
AMD’s prevalence increases with age. Intermediate and advanced stages of AMD affect nearly 15% of people over the age of 65, which translates to more than one million people in the UK. Additionally, the cost of AMD on the economy is significant. Annual costs related to AMD in the UK are approximately £11.1 billion.
The treatment options currently available for AMD are very limited. There are no approved treatments in Great Britain or Europe for geographic atrophy, which is the most common form of advanced dry AMD.
Therefore, the only treatments currently available for wet AMD require administration of injections directly into the eye and are, thus, a costly alternative for treating a significant number of people suffering from AMD. This has led to a number of studies on how to slow the progression of disease earlier so that patients do not lose their vision.
The study was conducted by Dr. Nick Beare of the University of Liverpool. His group used images of the retina collected as part of the Liverpool Diabetic Eye Screening Program, which routinely takes photos of diabetic patients.
Researchers evaluated the retinal images from more than 2,000 patients with type 2 diabetes over a five-year period and compared the patients who took metformin to those who did not. The researchers assessed the degree of AMD in the images using an established tool for grading AMD rather than relying on information from medical bills or insurance claims.
Researchers also adjusted their analysis to control for variables that could influence the outcomes, such as age, gender, and duration of diabetes.
The study’s findings are significant. For the patients taking metformin, the risk of developing intermediate AMD at the end of five years was 37% lower than those not taking metformin. The odds of developing intermediate AMD were statistically 0.63 times lower for patients taking metformin as compared to those not taking metformin.
Intermediate AMD is a critical point because although patients may be stable, the chance of progressing to sight-threatening disease begins to increase rapidly at the intermediate stage. Dr. Beare considered the results very promising.
As AMD has no treatment for most patients, this represents a large step forward in attempts to create new therapies for this condition. “All we need to do is conduct a clinical trial using metformin. Metformin has the potential to preserve sight in many people,” he added.
Metformin has been used as a first-line therapy for managing blood glucose levels in type 2 diabetes patients for many years. It acts to lower blood glucose levels by preventing the liver from producing glucose and by improving how the body processes and utilizes insulin.
In addition, metformin has an effect on aging. Metformin decreases inflammation and prevents oxidative damage. It also aids in the proper utilization of energy within the body.
Through its activation of autophagy, which clears away damaged cellular components that diminish with age, metformin may help to protect retinal cells against age-related damage prior to irreversible destruction.
The studies conducted on this population did not clearly identify a connection between metformin use and incidence of early stages of AMD or late-stage disease. Because of the small number of participants who progressed to having advanced AMD, it would have been difficult to observe differences between groups of patients regarding changes at that particular stage.
As the study was observational, it is impossible to state that metformin actually prevented the development of AMD in this population. The researchers were also not able to gather information about the dosage of metformin, dietary status, or vitamin supplementation for the entire cohort of patients.
In addition, the completeness of the smoking history was limited. However, the fact that this is the largest study performed to date on the development of retinal changes related to AMD, utilizing high-definition digital imaging over time, makes the results more accurate than previous studies that relied only on health care claims data and chart reviews.
Metformin is no longer protected under patent law and is affordable, costing approximately £50 per patient on an annual basis through the National Health Service in England. Side effects of metformin are mild and include transient nausea or diarrhea, and in some cases may result in renal injury if patients are dehydrated.
As metformin is a medication that has already established itself in the marketplace, testing for potential use in the prevention of AMD or in slowing its progression through clinical trials may proceed at an accelerated pace when compared to developing a novel therapy from the ground up.
Overall, the results provide an opportunity to delay a significant contributor to blindness, with the potential to develop safe and effective therapies based on commonly available medications.
Research findings are available online in the journal BMJ Open.
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