Diabetes continues to be a global healthcare challenge with profound effects on many systems of the body. Although cardiovascular disease gets top billing with regards to diabetic comorbidities, diabetic eye disease takes a hefty toll on patient quality of life robbing them of their ability to see their world.
The 3 primary causes of blindness in adults are open-angle glaucoma (OAG), age-related macular degeneration (AMD), and cataract.1 Diabetes affects the retina primarily, but recent evidence suggests that metformin, an oral medication used for type 2 diabetes may protect patients from OAG and AMD. Unlike cataract, OAG and AMD do not have a surgical cure and are currently irreversible causes of blindness.1
While metformin is used as an insulin sensitizing drug for type 2 diabetics with insulin resistance, the particular kinase it targets is also known to play a part in neurodegenerative diseases.2 Even though results point to a protective effect for metformin in AMD and OAG the prior studies were not designed to demonstrate causality. The authors of this study sought to illuminate the association between metformin and other diabetes medications including insulin and sulfonylurea derivatives with mitigating risk in OAG, AMD, and cataract. They drew data from the large prospective Rotterdam Study.
Ultimately, the study included 11,260 subjects with type 2 diabetes mellitus (T2D). Looking for an association between T2D and eye disease the authors found OAG in 7% of untreated T2D patients and in 1% of those treated with metformin.1 AMD was diagnosed in 20% of untreated T2D patients and in only 14% of those treated with metformin.1 Cataract was diagnosed in 45.6% of untreated T2D patients and 45.1% of patients treated with metformin.1
The authors found a statistically significant association between type 2 diabetes (T2D) and all three eye diseases.1 Looking at diabetes medication and eye disease, the authors found a significant association between metformin and a reduction in open angle glaucoma (OAG) when compared to no treatment.1 Treatment with insulin or a sulfonylurea also reduced the risk of developing OAG when compared to no treatment at all albeit to a lesser extent than metformin.1 All 3 diabetes medications were associated with a reduction in the risk for age-related macular degeneration (AMD) while none of the them were associated with a reduction in cataract cases.1
Ultimately the lifetime risk of AMD for patients taking metformin was similar to that of patients with untreated diabetes and participants without diabetes while those taking other diabetes medications had the lowest lifetime risk of AMD, even lower than those without diabetes.1 These data may either highlight the effect of insulin or sulfonylurea drugs on AMD risk or the relative rarity of the condition in the general population.
The primary finding of this prospective, population-based study was a significant association between T2D and OAG that was previously unclear.1 Further, the authors discovered a greater than 30% increase in risk of AMD with T2D.1 Joelle E. Vergoesen, MSc states,
“We not only found that metformin was associated with a lower risk of AMD, but we also observed lower frequencies of AMD for those taking other diabetes medication,” said Joelle Vergoesen, MSc.
As far as risk of mitigation metformin use was associated with a lower risk of OAG in T2D patients while taking other diabetic medications had a protective effect against OAG.1
These findings are exciting and further underscore the importance of diligent diabetes treatment. We have long known that treating diabetes primarily mitigates the risk for kidney disease and cardiovascular disease. Diabetic eye disease often takes a back seat to comorbidities that lead to however mortality, the morbidity associated with blindness is no less devastating or trivial. As clinicians we should strive to follow best practices including comprehensive diabetes care and medical management with the ultimate goal of tight and long-lasting glucose control in all of our patients.
- Sivandzade F, Prasad S, Bhalerao A, Cucullo L. NRF2 and NF-қB interplay in cerebrovascular and neurodegenerative disorders: molecular mechanisms and possible therapeutic approaches. Redox Biol. 2019;21:101059. doi:10.1016/j.redox. 2018.11.017