Metformin may have a protective effect against AMD

Metformin, a frequently prescribed drug to treat diabetes, could be a novel therapy for AMD.

Reviewed by Dimitra Skondra, MD, PhD.

A frequently prescribed drug to treat diabetes, metformin, may have the potential to be a novel therapy for age-related macular degeneration (AMD), reported Dimitra Skondra MD, PhD. She is Associate Professor of Ophthalmology and Visual Science, and Director of the J. Terry Ernest Ocular Imaging Center, Founder/Leader, Retina Microbiome Team, Vitreoretinal Service, The University of Chicago.

This protective effect is known to be present against other age-associated diseases, but the importance of such a finding in diabetes cannot be over-emphasized.

She and her colleagues conducted a retrospective case-control study to take a close look at the the relationship betweenmetformin and other antidiabetic medications in patients with AMD. The authors used a large health insurance claims database to identify patients who had been newly diagnosed with AMD between January 2008 and December 2017.

A total of 312,404 patients and 312,376 matched controls were included in the study.

Important finding: Metformin associated with reduced odds of AMD development

“We found that metformin use was associated with reduced odds of developing AMD (odds ratio [OR], 0.94 [95% CI, 0.92-0.96]), Dr. Skondra reported.

The low-to-moderate doses of metformin carried the greatest potential benefit. The former covers doses of 1-270 grams/2 years; OR, 0.91 [95% confidence interval [CI], 0.88-0.94]; and the latter 271-600 grams/2 years; OR, 0.90 [95% CI, 0.87-0.93]).

In contrast, doses that exceeded 1,080 grams/2 years were not associated with reduced odds of developing AMD.

Both the reduced ORs and the dose-dependent response were preserved in the diabetic patients-only cohort, that is, metformin was associated with a decreased OR of development of AMD in patients with diabetes who did not have diabetic retinopathy (OR, 0.93 [95% CI, 0.91-0.95]); however, this was not the case when patients also had diabetic retinopathy (OR, 1.07 [95% CI, 1.01-1.15]).

Another finding in the patients in the diabetic cohort was an independent protective effect against AMD development associated with the use of insulin (OR, 0.92 [95% CI, 0.90-0.95], P < 0.001), and sulfonylureas (OR, 0.94 [95% CI, 0.92-0.96], P < 0.001). When analyzed in combination with metformin versus neither of those medications, insulin (OR, 0.89 [95% CI, 0.83-0.97], P = 0.004) and sulfonylureas (OR, 0.91 [95% CI, 0.84-0.98], P = 0.01), the analysis showed a protective effect as well.

“Subjects taking insulin or sulfonylureas alone had a similar risk of developing AMD as those taking metformin alone (OR, 0.96 [95% CI, 0.89-1.01] and OR, 0.98 [95% CI, 0.90-1.05), respectively). Patients receiving exenatide, sitagliptin (Januvia, Merck), or pramlintide (Symlin, Bristol-Myers Squibb), other diabetic medications, had a higher risk of developing AMD (OR, 1.08 [95% CI, 1.05-1.11], P < 0.001), although when taken with metformin the increased risk was no longer seen (OR, 1.04 [95% CI, 0.97-1.13]).

Another finding was that subjects taking sulfonylureas with metformin had an even greater decreased risk of AMD development compared to those taking metformin alone (OR, 0.94 [95% CI 0.91-0.97], P < 0.001).

Dr. Skondra concluded,These data suggest that metformin may be a novel AMD therapeutic strategy and provide the basis for future studies.”