Effect of metformin on the development of age-related macular degeneration (AMD) in the Diabetes Prevention Program Outcomes Study (DPPOS)

Abstract

Purpose : Based on retrospective studies, metformin has been suggested to have a beneficial role in lowering the risk of AMD. The DPPOS is a follow-up phase of a large multicenter randomized clinical trial to investigate the effects of treatment with metformin or an intensive lifestyle modification (lifestyle), compared to placebo on preventing the onset of type 2 diabetes in a population at high-risk of developing diabetes. The DPPOS provides a unique opportunity to study the effects of metformin and lifestyle changes in preventing or delaying the development of AMD.

Methods : Color fundus photographs (FP) and optical coherences tomograms (OCT) were evaluated by the Wisconsin Reading Center in 1592 participants at year 16 of study follow up for presence and severity of diabetic retinopathy and AMD. AMD was classified as early, intermediate, or advanced (neovascular AMD or geographic atrophy) based on FP and OCT. Drusen size was classified as small, intermediate, or large. Differences in the prevalence and severity of AMD across the randomized groups were evaluated using Pearson’s Chi² test.

Results : Participants were randomly distributed between three interventional arms; 514 in the lifestyle arm, 549 in metformin, and 529 in the placebo arm. All 3 arms were balanced for baseline characteristics including age, gender, race, smoking habits, body mass index, and education level. AMD was identified in 479 (30.1%) participants; 229 (14.4%) had early, 218 (13.7%) intermediate and 32 (2.0%) had advanced AMD. There was no significant difference in the presence of AMD between the three groups: 29.6% in lifestyle, 30.2% in metformin, and 30.7% in the placebo (p = 0.93). There was also no difference in the distribution of early, intermediate, and advanced AMD between the intervention groups (p =0.095, Figure).

Conclusions : There was no statistically significant difference in the prevalence and severity of AMD between the three treatment groups after 16 years of follow-up. These data suggest neither metformin nor lifestyle changes for weight loss have a beneficial effect on lowering the risk of AMD. Additional observational analysis with cumulative years of metformin as main exposure is ongoing and may reveal further information.

This is a 2021 ARVO Annual Meeting abstract.

 

Distribution of AMD severity levels within the three study arms; Intensive lifestyle modification (Lifestyle), Metformin and Placebo