GLP-1 receptor agonists and diabetic retinopathy: A meta-analysis of randomized clinical trials

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are used to treat type 2 diabetes mellitus. Recent research suggests that GLP-1 RAs may influence diabetic retinopathy (DR). We searched ClinicalTrials.gov for trials comparing FDA-approved GLP-1 RAs to placebo, insulin, or oral antidiabetic medicine. Rates of DR, ocular adverse events, demographics, and clinical characteristics were compared amongst cohorts on 93 trials. GLP-1 RA use was significantly associated with increased risk of early-stage DR (risk ratio (RR) = 1.31, 95% confidence interval (CI) [1.01, 1.68]) and early-stage retinal adverse events (RR = 1.29, 95% CI [1.01, 1.66]) compared to placebo. Compared to insulin, GLP-1 RA use protected against late-stage DR (RR = 0.38, 95% CI [0.15, 0.98]). Analysis of individual GLP-1 RAs showed that albiglutide is responsible for these trends, as it is significantly associated with a higher risk of early-stage DR (RR = 2.18, 95% CI [1.01, 4.67]) compared to placebo and a lower risk of late-stage DR (RR = 0.25, 95% CI [0.09, 0.70]) compared to insulin. Albiglutide similarly affected retinal and ocular adverse events. Demographic analysis revealed significant differences between GLP-1 RA and comparator groups for age, HbA1c, body weight, BMI, duration of diabetes, sex, race, and ethnicity. The influence of GLP-1 RAs on DR and the eye may depend on the specific GLP-1 RA and patient demographic and clinical characteristics.