Impact of Glucagon-Like Peptide-1 Receptor Agonists on Age-Related Macular Degeneration at a Tertiary Ophthalmology Center

Objective

There is ongoing debate in the literature on the effects of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on age-related macular degeneration (AMD). This study examines the effect of GLP-1RA on the risk of AMD development compared with other glucose-lowering medications at a single ophthalmology center.

Design

Retrospective cohort study.

Subjects

A total of 30 515 GLP-1RA users, 48 906 sodium–glucose transport protein 2 inhibitor (SGLT-2i) users, 286 066 metformin users, and 164 361 insulin users aged ≥50 years had a 1-year minimum drug duration between 2016 and 2025. After propensity score matching (PSM), each cohort included 7561 patients. Patients with diabetic macular edema, severe or proliferative diabetic retinopathy, and with history of prior retinal surgeries were excluded.

Methods

The relative risk (RR) of developing nonexudative AMD was measured at yearly drug duration intervals up to 3 years using logistic regression models controlling for age, sex, race, smoking status, and hemoglobin A1C percentage. Manual review was performed on a random sampling of AMD cases to optimize accuracy. Cox proportional hazards (CPHs) validation analyses in PSM cohorts were performed, matching additionally for body mass index, history of hypertension, chronic kidney disease, and diabetes duration.

Main Outcome Measures

The primary outcome was the RR of nonexudative AMD up to 3 years on GLP-1RAs compared with alternative antihyperglycemic agents.

Results

Glucagon-like peptide-1 receptor agonist was associated with decreased risk of nonexudative AMD compared with metformin and insulin at all 3 years and compared with SGLT-2i only after 3 years of use (3 years: metformin relative risk [RR] = 0.25; 95% confidence interval [CI], 0.14–0.41; insulin RR = 0.28; 95% CI, 0.15–0.46; SGLT-2i RR = 0.42; 95% CI, 0.22–0.74). In PSM cohorts, CPH analyses showed a reduced risk only compared with insulin (hazards ratio = 0.45; 95% CI, 0.27–0.76).

Conclusions

Glucagon-like peptide-1 receptor agonist use was associated with a lower risk of nonexudative AMD compared with metformin, insulin, and SGLT-2i in logistic regression models. The risk reduction persisted for insulin in CPH analyses in smaller PSM cohorts.

Financial Disclosure(s)

Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.