Association of Diabetes Medication With Open-Angle Glaucoma, Age-Related Macular Degeneration, and Cataract in the Rotterdam Study

Abstract

Importance: Recent studies suggest that the diabetes drug metformin has a protective effect on open-angle glaucoma (OAG) and age-related macular degeneration (AMD). However, studies have not addressed the critical issue of confounding by indication, and associations have not been evaluated in a large prospective cohort.

Objective: To determine the association between diabetes medication and the common eye diseases OAG, AMD, and cataract and to evaluate their cumulative lifetime risks in a large cohort study.

Design, setting, and participants: This cohort study included participants from 3 independent cohorts from the prospective, population-based Rotterdam Study between April 23, 1990, and June 25, 2014. Participants were monitored for incident eye diseases (OAG, AMD, cataract) and had baseline measurements of serum glucose. Data on diabetes medication use and data from ophthalmologic examinations were gathered.

Exposures: Type 2 diabetes (T2D) and the diabetes medications metformin, insulin, and sulfonylurea derivatives.

Main outcomes and measures: Diagnosis and cumulative lifetime risk of OAG, AMD, and cataract.

Results: This study included 11 260 participants (mean [SD] age, 65.1 [9.8]; 6610 women [58.7%]). T2D was diagnosed in 2406 participants (28.4%), OAG was diagnosed in 324 of 7394 participants (4.4%), AMD was diagnosed in 1935 of 10 993 participants (17.6%), and cataract was diagnosed in 4203 of 11 260 participants (37.3%). Untreated T2D was associated with a higher risk of OAG (odds ratio [OR], 1.50; 95% CI, 1.06-2.13; P = .02), AMD (OR, 1.35; 95% CI, 1.11-1.64; P = .003), and cataract (OR, 1.63; 95% CI, 1.39-1.92; P < .001). T2D treated with metformin was associated with a lower risk of OAG (OR, 0.18; 95% CI, 0.08-0.41; P < .001). Other diabetes medication (ie, insulin, sulfonylurea derivates) was associated with a lower risk of AMD (combined OR, 0.32; 95% CI, 0.18 to 0.55; P < .001). The cumulative lifetime risk of OAG was lower for individuals taking metformin (1.5%; 95% CI, 0.01%-3.1%) than for individuals without T2D (7.2%; 95% CI, 5.7%-8.7%); the lifetime risk of AMD was lower for individuals taking other diabetes medication (17.0%; 95% CI, 5.8%-26.8% vs 33.1%; 95% CI, 30.6%-35.6%).

Conclusions and relevance: Results of this cohort study suggest that, although diabetes was clearly associated with cataract, diabetes medication was not. Treatment with metformin was associated with a lower risk of OAG, and other diabetes medication was associated with a lower risk of AMD. Proof of benefit would require interventional clinical trials.

Figure 1.. Association Between Diabetes Medication and Eye Diseases

Data presented as odds ratios (ORs) with 95% CIs for open-angle glaucoma (A), age-related macular degeneration (B), and cataract (C). All analyses are adjusted for age, sex, body mass index, use of antihypertensives, use of statins, and fasting serum glucose. The reference category were participants with diabetes who were not receiving treatment, unless otherwise stated. ^aOnly participants with diabetes.

Figure 2.. Cumulative Incidence of Eye Diseases as a Function of Age

Kaplan-Meier curves showing cumulative incidence of open-angle glaucoma (A), age-related macular degeneration (B), and cataract (C) of participants with diabetes treated with metformin and those treated with other diabetes medications, untreated participants with diabetes, and individuals without type 2 diabetes.