Metformin, Lifestyle Changes Not Associated With Risk of AMD

A clinical trial found that the prevalence of age-related macular degeneration (AMD) was not associated with the use of metformin.

A study published in JAMA Ophthalmology found that the use of metformin and lifestyle changes were not associated with the prevalence of age-related macular degeneration (AMD). Duration of metformin use was also not found to be associated with AMD.

AMD is the most common age-related eye condition in the United States and is a leading cause of blindness. The neovascular stage remains the only stage of AMD that can be treated with therapies. This current study examined the association between the prevention or delaying of the development of AMD and the use of metformin and lifestyle changes initiated to prevent diabetes.

This study used the Diabetes Prevention Program (DPP) for its data, which was a multicenter controlled clinical trial that enrolled patients with a risk of a diabetes diagnosis. The study separated the participants into 3 groups: a lifestyle intervention group focused on achieving physical activity of at least 150 minutes in a week; a metformin group that received 850 mg twice daily with a standard diet and exercise routine; and a double-blinded placebo group with standard diet and exercise.

The Diabetes Prevention Program Outcomes Study, which was a follow-up study to assess the association of the DPP interventions with outcomes, utilized fundus photographs and optical coherence tomography (SD-OCT) images to evaluate the association between AMD and metformin. The images were taken in 2018 in the 16th year of the follow-up. AMD was determined using these photographs.

There were 2051 participants who had attended the year 16 follow-up. Participants had a mean (SD) age of 49 (9) years and 71% were men. There were 1587 participants who had retinal imaging for this study, of whom 513 (32.3%) were in the lifestyle group, 546 (34.4%) were in the metformin group, and 528 (33.2%) were in the placebo group. No significant difference in age, sex, race and ethnicity, smoking status, or body mass index was found in these groups.

A higher proportion of patients in the placebo group had type 2 diabetes. Metformin was used for a median (IQR) of 0 (0-7) years in the lifestyle group, 18.5 (9.5-20.3) years in the metformin group, and 1.5 (0-8.5) years in the placebo group.

AMD was found in 479 participants (30%), with early-stage AMD accounting for 14.4%, intermediate AMD accounting for 13.7%, and advanced AMD accounting for 2%. AMD severity was agreed on between color photography and SD-OCT in 92.9% of all eyes.

Prevalence of AMD was found to be 29.6% in the lifestyle group, 30.2% in the metformin group, and 30.7% in the placebo group. Age was significantly higher in the AMD group compared with those without AMD (mean [SD] age, 51.4 [9.6] vs 48 [8.6] years). Smoking was associated with prevalence of AMD (odds ratio [OR], 1.3; 95% CI, 1.1-1.6).

Prevalence of AMD was 28.8% in patients who used metformin regardless of duration and was 33.5% in patients who had never used metformin. No association was found between the use of metformin and AMD. The mean number of years that metformin was used was not significantly different in patients who did and did not have AMD. The OR for the likelihood of AMD with the number of years that metformin was used was 1.0 (95% CI, 0.9-1.2).

There were some limitations to this study. The relationship between metformin and incidence or progression of AMD could not be assessed in this cross-sectional study. Out-of-study use of metformin could have affected the assessment of the relationship. The cohort was healthy overall. Generalizability was limited due to only including adults at a higher risk of a diagnosis of diabetes.

The researchers concluded that a relationship between the prevalence of AMD and the use of metformin could not be found.


Domalpally A, Whittier SA, Pan Q, et al. Association of metformin with the development of age-related macular degeneration. JAMA Ophthalmol. Published online December 22, 2022. doi:10.1001/jamaophthalmol.2022.5567

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