A recent study published in Investigative Ophthalmology & Visual Science evaluated whether the use of metformin is associated with reduced odds of developing new-onset dry age-related macular degeneration (AMD).
Give me some background first.
Metformin, a commonly prescribed oral diabetes medication, has shown potential as a preventive agent due to its anti-angiogenic, anti-inflammatory, and neuroprotective effects in the retina.
Additionally, it is inexpensive, widely available globally, and noninvasive with a low profile of adverse events.
Go on…
A previous study led by the same research group from The University of Chicago determined that doses of metformin up to 1080 g over 2 years were linked with decreased odds of developing new-onset AMD of any subtype (i.e., dry, wet, or unspecified).
Despite these findings, there are conflicting results from recent studies regarding the link between metformin use and the development of dry AMD.
Now, talk about the study.
In this peer-reviewed case-control study of patients from a nationwide insurance database, researchers examined 194,135 cases with diagnoses of new-onset AMD between 2008 and 2017 and matched these to 193,990 controls in the Merative MarketScan Commercial and Medicare Databases.
They also evaluated a diabetic subgroup with 49,988 cases and 49,460 controls.
Multivariable conditional logistic regressions were used to identify the risks of exposures in the development of dry AMD.
What were the primary outcome measures?
The main outcome measures of the study were odds ratios of developing dry AMD with metformin use.
Findings?
Investigators found that any metformin use was associated with reduced odds of developing dry AMD (odds ratio [OR]=0.97, 95% confidence interval [CI] 0.95-0.99).
This protective effect was observed for cumulative 2-year doses of metformin of 1-270 g (OR=0.93, 95% CI 0.90-0.97) and 271-600 g (OR=0.92, 95% CI 0.89-0.96).
These doses decreased the odds by 3 to 10% and 4 to 11%, respectively.
What about the diabetic subgroup?
In the diabetic subgroup, metformin use below 601 g over 2 years decreased the odds of developing dry AMD (1-270 g: OR=0.95, 95% CI 0.91-0.99 and 271-600 g: OR=0.92, 95% CI 0.89-0.96).
These doses decreased the odds of developing dry AMD by 1 to 9% and 4 to 11%, respectively.
And patients with diabetic retinopathy?
Interestingly, diabetic patients without diabetic retinopathy had decreased odds of developing dry AMD with any metformin use (OR=0.97, 95% CI 0.94-0.998).
This protective effect was also noted in cumulative 2-year metformin doses of 1-270 g (OR=0.96, 95% CI 0.91-0.998) and 271-600 g (OR=0.92, 95% CI 0.88-0.96).
Anything else?
The findings of this study did not support a metformin dose-response association in the development of dry AMD, as higher doses were not more protective against the development of AMD.
Notably, doses of metformin >1080 g were linked with increased odds of developing dry AMD (OR=1.06, 95% CI 1.02-1.11).
And this is because …?
This is potentially because patients who require the highest doses of metformin may have the most severe cases of diabetes and remain at an increased risk for dry AMD despite protection from metformin.
Expert opinion?
According to the study authors, “When assessing medication interactions, metformin in combination with sulfonylureas or statins decreased the odds of developing dry AMD compared to metformin alone, suggesting a potential synergistic effect.”
Sulfonylureas include drugs with the generic names of glimepiride, glyburide, glipizide, tolazamide, tolbutamide, and chlorpropamide.
Take home.
Per the study authors, these findings demonstrate that metformin use was correlated with decreased odds of developing dry AMD, particularly for cumulative 2-year doses below 601 g.
For diabetic patients without diabetic retinopathy (DR), a similar association was observed—indicating that metformin may be a noninvasive strategy for preventing the development of dry AMD.
Next steps?
Follow-up studies that expand on this work by analyzing the association between metformin use and the progression of dry AMD, particularly to advanced dry AMD or geographic atrophy (GA), are warranted.
Currently, there are phase 2 clinical trials assessing whether metformin use:
- Decreases GA progression (NCT02684578)
- As an intervention for primary open-angle glaucoma (POAG) (NCT05426044)
As an intervention for ABCA4 retinopathy/Stargardt disease (NCT04545736).