Relationship between Oral Metformin Use and Age-Related Macular Degeneration

Stewart, Jay M.; Lamy, Ricardo; Wu, Frances; Keenan, Jeremy D.

doi:10.1016/j.oret.2020.06.003

Cited by 27 publications

(55 citation statements)

References 7 publications

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“…The overall OR of any AMD from metformin use was 0.80 with 95% CI 0.54-1.05. In a sensitivity analysis, the OR remained stable and the upper limit of the confidence interval remained close to 1.0, affecting the statistical significance (removing study by Blitzer et al [34]: OR 0.75, 95% CI 0.52-0.97, P \ 0.001, I 2 = 87.1%; Stewart et al [33]: OR 0.82, 95% CI 0.53-1.12, P \ 0.001, I 2 = 99.1%; Brown et al [32]: OR 0.82, 95% CI 0.54-1.11, P \ 0.001, I 2 = 99.1%; Chen et al [35]: OR 0.87, 95% CI 0.70-1.05, P = 0.002, I 2 = 79.7%; Lee et al [36]: 0.72, 95% CI 0.44-1.01, P \ 0.001, I 2 = 99.1%).…”

Section: Meta-analysismentioning

confidence: 94%

“…The second study in the USA [33] gathered data from University of California San Francisco electronic medical record of people aged 60 years and older with diabetes, and having an ophthalmology encounter from April 2012 to August 2019. It reported that in 3120 patients, metformin was associated with decreased odds of any AMD (OR 0.70; 95% CI 0.55-0.88, P = 0.003) and non-neovascular AMD (OR 0.59; 95% CI 0.46-0.77, P \ 0.001) using propensity score-weighted logistic regression models.…”

Section: Literature Systematic Searchmentioning

confidence: 99%

“…We analysed 'any AMD' since all studies included all AMD, not only atrophic and neovascular AMD, but also unspecified form of macular degeneration (Supplementary Material B). Only one study presented data of an AMD subtype, non-neovascular AMD, in the analysis [33]. Thus, it is not possible to perform meta-analysis by classifying the AMD subtypes.…”

Section: Meta-analysismentioning

confidence: 99%

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Metformin, A Potential Role in Age-Related Macular Degeneration: A Systematic Review and Meta-Analysis

et al. 2021

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Background Currently, no generally approved medical treatment can delay the onset of age-related macular degeneration (AMD) or slow the progression of degenerative changes. Repurposing drugs with beneficial effects on AMD pathophysiology offers a route to new treatments which is faster, cost-effective, and safer for patients. Recent studies indicate a potential role for metformin in delaying AMD development and progression. In this context, we conducted a systematic review and meta-analysis to look for beneficial associations between metformin and AMD. Methods We systematically searched Medline and Embase (via Ovid), Web of Science, and ClinicalTrials.gov databases for clinical studies in humans that examined the associations between metformin treatment and AMD published from inception to February 2021. We calculated pooled odds ratio (OR) with 95% confidence interval (CI) considering a random effect model in the meta-analysis. Results Five retrospective studies met the inclusion criteria. There are no prospective studies that have reported the effect of metformin in AMD. The meta-analysis showed that people taking metformin were less likely to have AMD although statistical significance was not met (pooled adjusted OR = 0.80, 95% CI 0.54–1.05, I 2 = 98.8%). Subgroup analysis of the association between metformin and early and late AMD could not be performed since the data was not available from the included studies. Conclusions Analysis of retrospective data suggests a signal that metformin may be associated with decreased risk of any AMD. It should be interpreted with caution because of the failure to meet statistical significance, the small number of studies, and the limitation of routine record data. However prospective studies are warranted in generalizable populations without diabetes, of varied ethnicities, and AMD stages. Clinical trials are needed to determine if metformin has efficacy in treating early and late-stage AMD. Supplementary Information The online version contains supplementary material available at 10.1007/s40123-021-00344-3.

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Section: Meta-analysismentioning

confidence: 94%

Section: Literature Systematic Searchmentioning

confidence: 99%

Section: Meta-analysismentioning

confidence: 99%

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Metformin, A Potential Role in Age-Related Macular Degeneration: A Systematic Review and Meta-Analysis

et al. 2021

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“…Early retrospective studies on the effect of metformin exposure on development of AMD have shown mixed results. 17–20 Three studies, one case-control, one retrospective cohort, and one retrospective cross sectional, report that metformin exposure is associated with decreased AMD incidence. 17–19 In contrast, a third case-control study found no association with metformin exposure and AMD development.…”

Section: Introductionmentioning

confidence: 99%

“…17–20 Three studies, one case-control, one retrospective cohort, and one retrospective cross sectional, report that metformin exposure is associated with decreased AMD incidence. 17–19 In contrast, a third case-control study found no association with metformin exposure and AMD development. 20 Possibly contributing to the conflicting results is the fact that previous studies combined incident dAMD and neovascular AMD as the primary outcome of interest, rather than looking at these disease subsets with different pathogeneses separately.…”

Section: Introductionmentioning

confidence: 99%

Association of metformin and development of dry age-related macular degeneration in a U.S. insurance claims database

Eton

Wubben

Besirli

et al. 2021

European Journal of Ophthalmology

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Purpose: To assess whether metformin is associated with dry age-related macular degeneration (dAMD) development. Methods: In this retrospective cohort study, patients enrolled in a nationwide U.S. medical insurance claims database from 2002 to 2016 were included if they had diabetes mellitus, were ⩾55 years old, and were enrolled for ⩾2 years without a prior AMD diagnosis. The primary exposure was metformin use analyzed as either active or prior use or cumulative metformin dosage over the study period. A time updating Cox proportional hazard regression was used to estimate the hazard ratio of dAMD incidence with metformin exposure. Results: Among 1,007,226 diabetic enrollees, 53.3% were female and 66.4% were white with a mean hemoglobin A1c of 6.8%. Of eligible enrollees, 166,115 (16.5%) were taking metformin at the index date. Over the study period, 29,818 (3.0%) participants developed dAMD. In the active versus prior use of metformin model, active use conferred an increased hazard of developing dAMD (HR, 1.08; 95% CI, 1.04–1.12) while prior use had a decreased hazard (HR, 0.95; 95% CI 0.92–0.98). The cumulative metformin dosage model showed a significant trend toward increased hazard of dAMD incidence with increasing cumulative dosage ( p < 0.001), with the lowest dosage quartile having decreased hazard of dAMD incidence (HR, 0.95; 95% CI, 0.91–0.99) and the highest having increased hazard (HR, 1.07; 95% CI, 1.01–1.13). Conclusions: Small, conflicting associations between metformin exposure and development of dAMD were observed depending on cumulative dosage and whether drug use was active, suggesting metformin did not substantially affect the development of dAMD.

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Association of Metformin With the Development of Age-Related Macular Degeneration

et al. 2023

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ImportanceAge-related macular degeneration (AMD) is a leading cause of blindness with no treatment available for early stages. Retrospective studies have shown an association between metformin and reduced risk of AMD.ObjectiveTo investigate the association between metformin use and age-related macular degeneration (AMD).Design, Setting, and ParticipantsThe Diabetes Prevention Program Outcomes Study is a cross-sectional follow-up phase of a large multicenter randomized clinical trial, Diabetes Prevention Program (1996-2001), to investigate the association of treatment with metformin or an intensive lifestyle modification vs placebo with preventing the onset of type 2 diabetes in a population at high risk for developing diabetes. Participants with retinal imaging at a follow-up visit 16 years posttrial (2017-2019) were included. Analysis took place between October 2019 and May 2022.InterventionsParticipants were randomly distributed between 3 interventional arms: lifestyle, metformin, and placebo.Main Outcomes and MeasuresPrevalence of AMD in the treatment arms.ResultsOf 1592 participants, 514 (32.3%) were in the lifestyle arm, 549 (34.5%) were in the metformin arm, and 529 (33.2%) were in the placebo arm. All 3 arms were balanced for baseline characteristics including age (mean [SD] age at randomization, 49 [9] years), sex (1128 [71%] male), race and ethnicity (784 [49%] White), smoking habits, body mass index, and education level. AMD was identified in 479 participants (30.1%); 229 (14.4%) had early AMD, 218 (13.7%) had intermediate AMD, and 32 (2.0%) had advanced AMD. There was 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 arm. There was also no difference in the distribution of early, intermediate, and advanced AMD between the intervention groups. Mean duration of metformin use was similar for those with and without AMD (mean [SD], 8.0 [9.3] vs 8.5 [9.3] years; P = .69). In the multivariate models, history of smoking was associated with increased risks of AMD (odds ratio, 1.30; 95% CI, 1.05-1.61; P = .02).Conclusions and RelevanceThese data suggest neither metformin nor lifestyle changes initiated for diabetes prevention were associated with the risk of any AMD, with similar results for AMD severity. Duration of metformin use was also not associated with AMD. This analysis does not address the association of metformin with incidence or progression of AMD.

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Relationship between Oral Metformin Use and Age-Related Macular Degeneration

Cited by 27 publications

References 7 publications

Metformin, A Potential Role in Age-Related Macular Degeneration: A Systematic Review and Meta-Analysis

Metformin, A Potential Role in Age-Related Macular Degeneration: A Systematic Review and Meta-Analysis

Association of metformin and development of dry age-related macular degeneration in a U.S. insurance claims database

Association of Metformin With the Development of Age-Related Macular Degeneration

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