Despite Slight Increase in DR Incidence, Fewer Patients on GLP-1 Drugs Progressed or Develop Complications

GLP-1 receptor agonist use was associated with a 24.2% reduction in the risk of vision loss progressing to blindness, with 30.2% reduction in patients with preexisting DR. Photo: Carolyn Majcher, OD. Click image to enlarge. Given the rapidly increasing use of glucagon-like peptide-1 (GLP-1) receptor agonist therapy—and the attendant controversies that have followed—it’s important to continue to improve our understanding of the impact of these powerful medications. A retrospective cohort study of over 185,000 people prescribed these drugs showed that, while GLP-1 use was associated with a slight increase in incident diabetic retinopathy (DR), fewer patients experienced progression to sight-threatening stages of DR, developed retinopathic complications or required invasive treatments. These findings suggest that GLP-1 agonists may be a factor in reduced rate of vision loss leading to blindness, even among individuals with preexisting DR.“It is crucial that all patients with type 2 diabetes treated with GLP-1 RAs, regardless of preexisting DR, receive regular screening and monitoring for potential diabetic complications,” the study authors wrote in their paper in JAMA Network Open.This retrospective cohort study of adults (aged ≥18 years) with type 2 diabetes and a recent hemoglobin A1c level of 6.5% or higher during a seven-year period was conducted using the TriNetX database. After propensity score matching, 185,066 individuals (mean age, 59.0 years; 50.5% women) were prescribed GLP-1 receptor agonists. The study investigated whether GLP-1 use is associated with the development of DR, nonarteritic anterior ischemic optic neuropathy (NAION) or DR complications in patients with type 2 diabetes. For a good overview of the optometrist’s role in diabetic retinopathy care, see this recent feature by Carolyn Majcher, OD. Although the use of GLP-1 agonists was associated with a modest increase in the rate of incident DR (0.2% increase) over two years, the absolute number of new DR diagnoses was low at 2.7%.Use of GLP-1 drugs was associated with a slight increased incidence of DR (hazard ratio; HR: 1.07), while no statistically significant difference was observed in the risk of NAION (HR: 1.26). In a subgroup analysis of 32,695 patients with preexisting DR, GLP-1 agonists were not associated with progression to proliferative DR (HR: 1.06) or diabetic macular edema (HR: 0.98) but were associated with a lower occurrence of vitreous hemorrhages (HR: 0.74), neovascular glaucoma (HR: 0.78) or blindness (HR: 0.77).The study found that many interventions for DR, including intravitreal injections, panretinal laser photocoagulation and vitrectomy for DR, were less frequently needed by patients with GLP-1 receptor agonist prescriptions compared with those without such prescriptions. It also found a lower rate of initiation of treatment with anti-VEGF inhibitors.The researchers noted that their study was also limited by the lack of longitudinal HbA1c measurements at fixed time intervals that would allow assessment of glycemic changes over the follow-up period.“As a result, we could not directly evaluate the potential implications of rapid glucose lowering for the observed outcomes, a mechanism hypothesized to contribute to the initial worsening of DR with GLP-1 RA use,” they wrote.The team was also unable to determine the precise number of individuals excluded due to inadequate follow-up. The analysis did not capture data on the switching or discontinuation of GLP-1 agonists, which may affect treatment patterns and outcomes. Additionally, certain demographic groups, such as Asian, Black and Hispanic individuals or patients with lower income, were less likely to receive GLP-1 agonist prescriptions. The researchers also acknowledged that they did not control for other retinal conditions unrelated to diabetes that may have required treatment.The researchers concluded that future studies should examine how compliance and adherence affect effectiveness endpoints to improve understanding of the clinical effectiveness outcomes of GLP-1 receptor agonists.Click here for the journal source. Ramsey DJ, Makwana B, Dani SS, et al. GLP-1 receptor agonists and sight-threatening ophthalmic complications in patients with type 2 diabetes. JAMA Netw Open. 2025;8(8):e2526321. This article was developed by the editorial staff in conjunction with experts in the field. In the process, AI may have been among the editorial tools used to meet the goals of human editors, who approved all content.