Abstract
Purpose :
Prior studies have reported that the incidence of age-related macular degeneration (AMD) is reduced in diabetes mellitus (DM) patients with a history of metformin usage. That metformin can slow progression of geographic atrophy is the subject of an ongoing clinical trial (NCT02684578). But not all studies have reported a beneficial effect of metformin in AMD diagnosis. We recently performed a genome-wide association study for AMD and showed that polygenic risk has poor transferability in multi-ethnic samples. Thus, the chance that genetic ancestry or predisposition impacts the relationship between AMD and metformin exposure has not been addressed. We examined these questions in the VA Million Veteran Program (MVP) biobank.
Methods :
We included MVP participants with a history of DM (17,062 cases with AMD and 140,944 controls). Duration and cumulative dose of metformin use were the main exposures. Risk modifiers included genetic ancestry and AMD polygenic risk score (PRS). AMD case or control status was the main outcome and was determined by ICD code-based algorithm. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using multivariable logistic regression-models adjusted for potential confounders (age, gender, duration of DM, lipid profile, sulfonylurea, insulin use); sensitivity analyses were performed for HbA1C.
Results :
Of 158,006 patients with DM, 96.2% were male, 60.6% were non-Hispanic white (NHW), 18.0% were non-Hispanic black (NHB) and 6.5% were Hispanic (HIS). In comparison to NHW, NHB and HIS status were associated with a decreased risk of AMD. Metformin use was associated with a modest decrease in risk of AMD (OR 0.96 [95%CI: 0.95, 0.97 per year of use]) while sulfonylurea use was associated with increased AMD risk. Unsurprisingly, increased risk of AMD was associated with a higher AMD PRS, but metformin did not display differential risk across the AMD PRS spectrum.
Conclusions :
In the U.S. Veteran population, a decreased risk of AMD was associated with metformin use. This decrease was comparable across different genetic ancestries and for different levels of genetic risk. These results support further evaluation of metformin as a treatment for AMD.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.