Summary: Metformin, a commonly used medication for diabetes, shows promise as a non-invasive treatment for geographic atrophy (GA), a severe form of age-related macular degeneration (AMD). Recent studies suggest metformin may reduce the risk of developing GA, with a stronger protective effect in non-diabetic individuals. This opens new possibilities for managing GA, a condition with limited treatment options, and highlights metformin’s potential beyond diabetes care.
Geographic atrophy (GA) is an advanced form of age-related macular degeneration (AMD), which affects the central retina or macula, leading to progressive and irreversible vision loss. Unlike regular AMD, which includes both dry (non-exudative) and wet (exudative) forms, GA is specifically a subtype of late-stage dry AMD. In GA, there is a slow degeneration of retinal pigment epithelial (RPE) cells and photoreceptors, resulting in well-defined areas of atrophy. This atrophy causes blind spots in the central vision (scotomas), which gradually enlarge over time, significantly impacting daily activities such as reading or recognizing faces.
Key Differences from Regular AMD
Regular dry AMD often progresses slowly, with drusen deposits under the retina, but it may remain stable without leading to severe vision loss. GA, however, represents a more rapidly progressing and debilitating stage where atrophy of retinal cells is prominent. It differs from wet AMD, which is characterized by abnormal blood vessel growth and leakage beneath the retina.
Prevalence and Risk Factors
GA is estimated to affect around 1 million people in the United States and is a leading cause of blindness in the elderly. It predominantly occurs in people over 60, and risk factors include age, genetics (particularly variants of the complement factor H gene), smoking, and light exposure. About 20% of patients with dry AMD will eventually progress to GA, making it a critical subtype in the spectrum of AMD.
Challenges and Current Treatments
GA presents unique challenges due to the lack of effective treatment options to halt or reverse the atrophy. Current treatments for wet AMD, such as anti-VEGF injections, do not apply to GA. However, emerging therapies like complement inhibition (targeting inflammation and immune pathways) and gene therapy are being explored. Management often focuses on supportive care, including vision aids and lifestyle adjustments.
Metformin’s Protective Role Against Geographic Atrophy
Recent studies have begun to explore the protective effect of metformin, a well-known antidiabetic medication, against GA. A significant study titled The Association Between Metformin Use and New-Onset ICD Coding of Geographic Atrophy investigated metformin’s potential to prevent the development of GA, offering new hope for non-invasive treatment options.
Study Design and Key Findings
The research was a case-control study using data from the Merative MarketScan Commercial and Medicare Databases from 2017 to 2021. It included:
- Total cases: 10,505 patients aged 60 years and older with new-onset ICD coding of GA.
- Non-diabetic cohort: A separate analysis of 7,611 cases and 7,608 controls without diabetes.
Protective Effect of Metformin
- In the full sample, metformin use was associated with a 12% reduction in the odds of developing GA (Odds Ratio [OR]: 0.88, 95% Confidence Interval [CI]: 0.79–0.99).
- In the non-diabetic population, the protective effect was even more pronounced, showing a 47% reduction in odds of GA onset (OR: 0.53, 95% CI: 0.33–0.83).
Clinical Significance
The study essentially suggests that while metformin is useful for AMD as well as a very specific subtype of AMD called geographic atrophy, metformin is 4 times more likely to work in the case of GA when the patient is also non-diabetic. If one considers that GA does not have great treatment modalities unlike regular AMD, it makes the positive results with metformin even more important.
Potential Mechanisms
Metformin’s protective effect might be linked to its antioxidative and anti-inflammatory properties. It stimulates the AMP-activated protein kinase (AMPK) pathway, which protects photoreceptors and RPE cells from oxidative stress—one of the key mechanisms implicated in GA pathogenesis.
Key Takeaway
-Geographic Atrophy is rapidly progressing and severe and affects about 1 million people in the USA with few treatments
– Metformin will help prevent GA in about 1/8th of individuals with diabetes but can prevent about half the cases in non- diabetics individuals
– Based on this article and the numerous benefits metformin provides for non-diabetic individuals, it will likely be prescribed to all adults once large scale are concluded
Disclaimer: This article is for informational purposes only and does not substitute professional medical advice. Always consult a qualified healthcare provider for guidance tailored to your health situation.
At CanadianInsulin, we’re dedicated to providing up-to-date information and quality medications to support your health needs. Explore our range of GLP-1 receptor agonists and consult with our pharmacists for more information.
