Highlight
- Metformin use for 5 or more consecutive years was associated with a 32% reduced risk of developing AMD in diabetic patients.
- The protective effect was significant for dry AMD; a non-significant trend was observed in wet AMD.
- Statin use also correlated with decreased AMD risk, whereas insulin did not.
- Exclusion of patients with prior drusen attenuated protective associations, suggesting potential benefits throughout AMD progression.
Study Background and Disease Burden
Age-related macular degeneration (AMD) is a leading cause of vision loss among older adults worldwide, resulting in significant morbidity and diminished quality of life. Individuals with diabetes face heightened risks for vascular and retinal complications, potentially exacerbating AMD risk. Currently, effective preventive strategies against AMD, especially the dry form, remain limited. Metformin, a first-line therapy for type 2 diabetes, has demonstrated pleiotropic effects including anti-inflammatory and antioxidative properties, raising interest in its potential to mitigate AMD development. This study investigates whether long-term metformin exposure reduces AMD incidence in diabetic patients, addressing a pressing clinical need for preventive interventions in this vulnerable population.
Study Design
Researchers conducted a retrospective cohort study leveraging data from a federated health research network. The cohort included 7496 diabetic patients aged 60 or older who had attended at least two eye care visits separated by a minimum of one year, with no diagnosis of AMD at baseline. Patients who had used metformin at least once annually for 5 or more consecutive years prior to their eye visit (n=3748) were matched by propensity scores to 3748 patients who used metformin fewer than 5 consecutive years or never used it. The primary endpoint was incident AMD diagnosed after the second eye care visit. Secondary analyses examined AMD subtypes (dry vs wet) and the effect of other medications such as statins and insulin.
Key Findings
The study reported a significantly lower proportion of AMD development among long-term metformin users compared to non-users or short-term users (3.3% vs 4.9%). Metformin use was associated with a 32% reduced hazard of developing AMD (HR 0.68, 95% CI 0.54–0.85). This protective effect was confined to dry AMD (HR 0.69, 95% CI 0.53–0.90), with only a non-significant trend observed for wet AMD. Notably, patients taking metformin for 6 or more consecutive years also demonstrated reduced risk.
Additional analysis revealed that the use of statins was also correlated with lower AMD risk, whereas insulin usage did not confer such benefits. When patients with prior drusen—a biomarker indicating early AMD changes—were excluded, the benefits of metformin were less pronounced, suggesting metformin’s effects may be most potent in the prevention phase or early disease stage but may also extend through the disease course.
Expert Commentary
These findings support a potentially important role of metformin as a preventive agent against AMD in diabetic patients, aligning with its known anti-inflammatory and antioxidant mechanisms that could protect retinal tissues from degeneration. However, the retrospective design and reliance on electronic health records introduce potential confounding and misclassification bias. The attenuation of protective effects after excluding patients with drusen warrants further prospective or interventional studies to define the timing and extent of metformin’s benefits in AMD development. Additionally, given statins’ observed association, a synergistic or independent role in AMD prevention merits exploration.
Conclusion
This large database study provides compelling evidence that long-term metformin use among diabetic patients is associated with a significantly reduced risk of incident AMD, particularly the dry form. These findings highlight a promising, readily available pharmacologic intervention that may prevent or delay AMD in a high-risk population. Future randomized controlled trials are essential to confirm causality, optimize treatment duration, and understand underlying mechanisms. Clinicians may consider the potential ophthalmologic benefits of metformin when managing patients with diabetes, alongside established cardiovascular indications.
References
Hong AT, Luu IY, Keenan JD, Stewart JM. Long-Term Metformin Use and Reduced Risk of Age-Related Macular Degeneration: A Large Database Study. Ophthalmol Retina. 2025 Aug 11:S2468-6530(25)00354-9. doi: 10.1016/j.oret.2025.07.018. Epub ahead of print. PMID: 40803555.