Metformin Usage Not Associated with Age-Related Macular Degeneration Development

The data from the DPPOS cohort report no difference in AMD presence or severity between metformin, intensive lifestyle intervention, and placebo arms.

The long-term use of metformin may not be associated with the development of age-related macular degeneration (AMD), according to new research published in JAMA Ophthalmology.

The findings report no association of metformin use with the presence or severity of AMD, as well as no association between any use or metformin or number of years of metformin with AMD.

Retinal images were acquired and AMD was evaluated as part of an annual follow-up visit at year 16 of the Diabetes Prevention Program Outcomes Study (DPPOS). Investigators noted the unique opportunity to study the association of metformin and lifestyle changes with preventing or delaying the development of AMD.

“Until randomized data are available, the DPPOS provides strong evidence that does not support the use of metformin in the treatment of any stage of AMD,” wrote study author Amitha Domalpally, MD, PhD, The DPP Coordinating Center, The Biostatistics Center, Milken Institute School of Public Health, The George Washington University.

Retrospective studies have indicated that metformin may play a role in AMD treatment, by providing a protective effect against progression to late AMD. However, these studies have been based on retrospective electronic medical records data with inconclusive findings.

The DPPOS is a follow-up study to understand the long-term association of the Diabetes Prevention Program interventions with outcomes, with 2776 of participants continuing the study. As part of DPPOS, fundus photographs and spectral-domain optical coherence tomography (SD-OCT) images were collected at the follow-up visit in 2018.

The primary analysis studied the association between treatment arms and prevalence of AMD. Logistic regression adjusted for age, sex, self-reported race and ethnicity, and treatment groups was used to assess the association of metformin and lifestyle interventions with the risk of AMD. Analysis took place between October 2019 and May 2022.

Overall, 2051 participants attended the annual checkup at DPPOS year 16 with 664 from the lifestyle group, 696 from the metformin group, and 691 from the placebo group. Retinal imaging was available in 1592 participants (77.6%)

All arms were balanced for baseline characteristics including age (mean age at randomization, 49 years), sex (1128 male [71%] male), race and ethnicity (784 [49%] White), smoking habits, body mass index, and education level.

Through multimodal imaging, AMD was identified in 479 participants (30%); early-stage AMD in 229 participants (14.4%), intermediate AMD in 218 participants (13.7%), and advanced AMD in 32 participants (2%).

The findings indicate no significant difference in the presence of AMD between the 3 groups: 152 (29.6%) in the lifestyle arm, 165 (30.2%) in the metformin arm, and 162 (30.7%) in the placebo group. There were no differences in AMD presence or severity between the 3 treatment arms.

Investigators noted the mean duration of metformin use was similar for those with and without AMD (mean, 8.0 vs. 8.5 years; P = .69). In the adjusted model, history of smoking was the only variable significantly associated with prevalence of AMD (odds ratio [OR], 1.3; 95% CI, 1.1 - 1.6); P = .02).

The study, “Association of Metformin with the Development of Age-Related Macular Degeneration,” was published in JAMA Ophthalmology.