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

Abstract

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.

Association of lipid-lowering drugs and antidiabetic drugs with age-related macular degeneration: a meta-analysis in Europeans

“…Some studies reported metformin use to be associated with reduced odds of prevalent [20] or incident AMD [21,61,62], yet others could not confirm a relationship. [51,63] Blitzer et al described the largest benefit of metformin at a low to moderate dosage, indicating a U-shaped dose-response and hypothesized that a high dose may have been indicated in patients with poorly controlled diabetes who hence may benefit less from metformin use. Subsequently, a recent meta-analysis on retrospective data suggested a trend of reduced risk for AMD in patients using metformin without reaching statistical significance, underscoring the scarcity of data and highlighting the need for further prospective studies.…”

Metformin and retinal diseases in preclinical and clinical studies: Insights and review of literature

“…Data from retrospective studies are mixed but overall promising. [15][16][17][18]50,51 A large case-control study by our group revealed that metformin use was associated with reduced odds of developing age-related macular degeneration in a dose-dependent manner (OR, 0.93; 95% CI = 0.91-0.95), with low to moderate doses showing the greatest potential benefit. 312,404 patients with newly diagnosed AMD and 313,376 control patients matched on the following criteria: age, anemia, HTN, geography US region, and Charlson comorbidity index (CCI) score (0, 1, 2, or 3+) were identified from the IBM MarketScan Commercial and Medicare Supplemental Databases.…”

“…Even when categorizing patients based on treatment duration, metformin use did not demonstrate a protective effect (>300 days metformin use adjusted OR 0.93;95% CI = 0.68-1.26). 50 A recent retrospective cohort study by Eton et al 51 found that metformin was not protective against the development of dry AMD (dAMD). The authors queried a national US medical insurance claims database between January 2002 and December 2016 to identify an initial cohort of 1,007,226 diabetic patients 55 or older with no previous diagnosis of AMD, no history of DR or treatment for DR, and no other underlying retinal diseases.…”

Influence of metformin on age-related macular degeneration

“…Eight retrospective studies have analyzed the association of metformin use with AMD, of which one was a crosssectional study [39], four were cohort studies [40][41][42][43], two were case-control studies [44,45], and one was a nested case-control study [46]. Five studies exclusively determined the association between metformin use and the risk of developing AMD in diabetic patients [39][40][41][42][43], whereas three studies included broader patient groups according to their cohort definition [44][45][46]. One study examined the association of metformin use with dry AMD only [43], while the remaining studies considered all forms of AMD or did not further specify.…”

“…Five studies exclusively determined the association between metformin use and the risk of developing AMD in diabetic patients [39][40][41][42][43], whereas three studies included broader patient groups according to their cohort definition [44][45][46]. One study examined the association of metformin use with dry AMD only [43], while the remaining studies considered all forms of AMD or did not further specify. All other antidiabetic drugs studied showed no association.…”