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

Abstract

IMPORTANCERecent 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 PARTICIPANTSThis 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 MEASURESDiagnosis and cumulative lifetime risk of OAG, AMD, and cataract. RESULTSThis 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 RELEVANCEResults 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.

Association Between Oral Metformin Use and the Development of Age-Related Macular Degeneration in Diabetic Patients: A Systematic Review and Meta-Analysis

“…The full texts of 32 studies were retrieved for assessment of eligibility, with 9 studies remaining in the final quantitative meta-analysis. 12 – 20 …”

“…The included studies consisted of one cross-sectional, 19 three case‒control, 12 , 13 , 18 and five cohort studies. 14 – 17 , 20 Eight studies were retrospective in design, 12 – 19 and one was conducted prospectively. 20 Four studies were performed in the United States, 12 , 13 , 15 , 19 three in Asia, 14 , 17 , 18 and the other two in Europe.…”

“… 14 – 17 , 20 Eight studies were retrospective in design, 12 – 19 and one was conducted prospectively. 20 Four studies were performed in the United States, 12 , 13 , 15 , 19 three in Asia, 14 , 17 , 18 and the other two in Europe. 16 , 20 Seven studies obtained a diagnosis of DM with International Classification of Diseases (ICD) codes, 12 – 15 , 17 – 19 one with database read codes, 16 and one with medical records.…”

“… 20 Four studies were performed in the United States, 12 , 13 , 15 , 19 three in Asia, 14 , 17 , 18 and the other two in Europe. 16 , 20 Seven studies obtained a diagnosis of DM with International Classification of Diseases (ICD) codes, 12 – 15 , 17 – 19 one with database read codes, 16 and one with medical records. 20 Four studies exclusively enrolled patients with type 2 DM, 14 , 16 , 17 , 20 whereas 5 studies also recruited patients with type 1 DM.…”

“… 16 , 20 Seven studies obtained a diagnosis of DM with International Classification of Diseases (ICD) codes, 12 – 15 , 17 – 19 one with database read codes, 16 and one with medical records. 20 Four studies exclusively enrolled patients with type 2 DM, 14 , 16 , 17 , 20 whereas 5 studies also recruited patients with type 1 DM. 12 , 13 , 15 , 18 , 19 Seven studies investigated the outcome of incident AMD, 12 – 19 whereas one study aimed for both incident and prevalent AMD.…”