JAMA Ophthalmology, March 2021
Metformin, widely prescribed for diabetes, has been found to lower the risk of developing several age-related diseases, including cardiovascular disease. Blitzer et al. set out to determine whether a similar protective effect could be found with regard to age-related macular degeneration (AMD). They found that it was associated with reduced odds of developing AMD, with the greatest benefit at low to moderate doses of metformin and in the absence of coexisting diabetic retinopathy (DR).
For this case-control study, the researchers used data derived from a large U.S. health insurance claims database. They identified 312,404 participants who met the case inclusion criteria for AMD and an additional 312,376 controls who were matched 1:1 based on such factors as age and the presence of anemia and/or hypertension. All participants were age 55 or older.
Patients with AMD were slightly more likely to have diabetes than were controls (26% and 25.5%, respectively). The percentage of those with hypertension (65.1%) was the same for both groups, and the number with anemia was roughly equivalent (6.5% for those with AMD, vs. 6.4% for controls). Those with AMD were more likely to smoke (5.7%, vs. 4.9% of controls) and to have hyperlipidemia (49.6%, vs. 48.8% of controls). In addition, patients with AMD were more likely to have nonproliferative DR (3.7%, vs. 1.7% of controls) or proliferative DR (0.7%, vs. 0.4% of controls).
The use of metformin for more than two years reduced the odds of developing AMD, with an odds ratio (OR) of 0.94 (95% confidence interval [CI], 0.92-0.96; p < .001). This was particularly true for low to moderate doses: A dose of 1-270 g over two years had an OR of 0.91 (95% CI, 0.89-0.94); the finding was similar for doses of 271-600 g. In contrast, doses of 601-1,080 g had an OR of 0.95 (95% CI, 0.92-0.98), and doses greater than 1,080 g did not reduce AMD incidence. As for the presence or absence of DR, metformin use reduced the odds of developing AMD only in those diabetic patients who did not have DR (OR, 0.93 [95% CI, 0.91-0.95]; p < .0001). In contrast, patients who had diabetes and DR and were taking metformin were at greater risk of developing AMD (OR, 1.07 [95% CI, 1.01-1.15]; p < .03).
This study has several limitations, the authors acknowledge. Nonetheless, the study results suggest that metformin may have a role in preventing or slowing the progression of AMD, and they called for future studies on the issue. (Also see related commentary by Myra B. McGuinness, MBiostat, PhD, Jessica Kasza, BSc, PhD, and Robyn H Guymer, MBBS, PhD, in the same issue.)
The original article can be found here.