In American adults over the age of 50, AMD is the leading cause of unavoidable blindness. There are no effective protective measures against the disease, and there are no cures for the nonexudative form, which is the cause of most cases.
Metformin is the most common oral antihyperglycemic drug prescribed for patients with diabetes, the researchers wrote, and has been shown to have antiaging and protective effects against age-related diseases. The drug has previously been shown to reduce the risk of primary open-angle glaucoma, along with stroke, cancer and depression.
“Metformin acts directly and indirectly on a number of targets,” the authors explained, “including 5 ′ adenosine monophosphate-activated protein kinase (AMPK), a mammalian rapamycin target (mTOR), and sirtuin-1 (SIRT1) to influence important cell functions, such as survival, stress protection, autophagy, oxidative stress, protein synthesis, and inflammatory response. “
To determine the impact of metformin on the risk of developing AMD, the researchers conducted a case-control study using anonymous data from IBM’s Medicare MarketScan Commercial and Supplemental Market. Together, the databases “represent the annual health services of approximately 30 to 50 million employees, dependents, and retirees each year in the United States with additional primary or Medicare coverage through plans privately insured health. ”
Patient and patient prescription drug registration records and claims registered between January 2006 and December 2017 were included in the analysis. All participants (n = 312,404) 55 years or older, had re-diagnosed AMD, and at least 2 eye examinations in the previous 12 months.
A control group (n = 312,376) from the general population in MarketScan data was matched 1: 1 to a group of patients based on age, anemia, hip tension, area, and Charlson Comorbidity Index (CCI) score ). “Patients with exposures [to metformin] at least 1 outpatient medication application was required for medication within 2 years prior to the index date, ”the authors wrote.
Compared with the total control pool (n = 31,343,467), patients with AMD tended to be older and living in the Northeastern and Central U.S. regions, and were more likely to have hip-suffering, anemia , and get a higher CCI score.
Studies have shown that:
- There was a slightly higher percentage of diabetic participants (81,262 participants) in the case group [26.0%]) compared with the control group (79,497 participants [25.5%]).
- Metformin use was associated with lower numbers of developing AMD (OR, 0.94 [95% CI, 0.92-0.96]).
- Moderately low doses of metformin showed the greatest possible benefit (dosages over 2 years: 1-270 g: OR, 0.91 [95% CI, 0.88-0.94]; 271-600 g: NO, 0.90 [95% CI, 0.87-0.93]; 601-1080 g: NO, 0.95 [95% CI, 0.92-0.98]).
- Doses of more than 1080 g of metformin did not decrease over 2 years against the development of AMD.
- Both the reduction in OR and the dose-dependent response were retained in a cohort consisting of only diabetic patients.
When it comes to the frequency of diabetic retinopathy, researchers found that “metformin use was associated with lowering OR of AMD in diabetic patients unrelated to diabetic retinopathy (OR, 0.93 [95% CI, 0.91-0.95]) but was a risk factor in patients with diabetic retinopathy (OR, 1.07 [95% CI, 1.01-1.15]). ”
Future studies should be conducted to better determine the molecular pathways involved in the immune product that may be observed in this study. Due to the design of the current study, researchers were unable to determine the likelihood of AMD development, indicating a limitation. In addition, some patient characteristics including demographic and medical information were not taken into account, making it possible for racial differences among patients taking metformin vs. the patient. those who do not.
“If the protective effect of metformin is proven in clinical trials, this could lead to a new therapeutic strategy for this disease,” the authors concluded.
Information
Blitzer AL, Ham SA, Colby KA, Skondra D. Association of metformin use with age-related macular degeneration: a case-control study. Ophthalmol JAMA. Published online January 21, 2021. doi: 10.1001 / jamaophthalmol.2020.6331