Association of GLP1-Receptor Agonists With Diabetic Retinopathy

We aimed to examine the association between glucagon-like peptide-1 receptor agonists (GLP1-RA) use and diabetic retinopathy and non-arteritic anterior ischemic optic neuropathy (NAION), using dipeptidyl peptidase-4 inhibitors (DPP4i) as active comparators.

We created a retrospective propensity score (PS)-matched cohort study of patients who initiated either GLP1-RA or DPP4i (years 2006-2021). Using new-users, we created two PS-matched cohorts: patients with diabetes (overall cohort) and patients with diabetes and chronic kidney disease (CKD-cohort); the latter represents patients at higher likelihood of diabetes microvascular complications. Primary outcomes were non-vision-threatening diabetic retinopathy (NVTDR), vision-threatening diabetic retinopathy and diabetic macular edema (VTDR/DME), and NAION. Secondary outcomes included vision impairment or blindness and occurrence of retinopathy procedures.

PS-matched overall cohort included 98 082 pairs of GLP1-RA or DPP4i users. GLP1-RA users had higher risk of NVTDR (11.05% vs. 9.98%; odds ratio [OR] 1.12, 95% confidence interval [95% CI]: 1.09-1.15), VTDR/DME (2.17% vs. 1.98%; OR 1.09, 95% CI: 1.03-1.16), and occurrence of retinopathy procedures (4.16% vs. 3.68%, OR 1.14, 95% CI: 1.09-1.19). There was no significant difference in risk of NAION (OR 1.11, 95% CI: 0.96-1.29) or vision impairment or blindness (OR 1.04, 95% CI: 0.97-1.11). In the CKD cohort (15 440 matched pairs), GLP1-RA was associated with high risk of NVTDR (OR 1.10, 95% CI: 1.03-1.18), and occurrence of retinopathy procedures (OR 1.14, 95% CI: 1.03-1.26), but not other outcomes.

GLP1-RA use was associated with a modest increase in risk of diabetic retinopathy and retinopathy-related procedures, independent of the presence of retinopathy at baseline. However, GLP1-RA use was not associated with vision impairment or blindness, although administrative codes notably have low validity for blindness diagnosis.