No Difference Seen in Risk of Sight-threatening DR Among GLP-1 Drugs

Given the rapidly increasing use of GLP-1 agonist pharmacotherapy, it is important to continue to improve our understanding of the impact of these powerful medications, as clinical trials have thus far provided limited and conflicting evidence on potential retinal risks. Photo: Novo Nordisk. Click image to enlarge.  The substantial increase in glucagon-like peptide-1 (GLP-1) receptor agonist agent use among patients with type 2 diabetes has been important to reduce systemic health risks; however, there is conflicting evidence regarding the impact of these medications on sight-threatening diabetic retinopathy (DR) complications. All FDA-approved GLP-1 medications have demonstrated improved fasting blood glucose and HbA1c reductions compared to placebo; however, there are known differences between semaglutide, dulaglutide, liraglutide and exenatide in the magnitude of these effects.A recent study published in Ophthalmology Retina evaluated the relative risk associated with initiating GLP-1 agonist pharmacotherapy with these drug options on developing sight-threatening DR in routine clinical practice for patients with type 2 diabetes at moderate cardiovascular risk, which was defined as an annualized 1% to 5% predicted risk of experiencing a major adverse cardiovascular event. In a cohort of over 150,000 patients, the researchers identified no difference in the risk following initiation of different GLP-1 agents among these adults, despite the differences in systemic efficacy among the examined GLP-1 receptor agonist medications.The researchers performed a retrospective observational study of over 150,000 adult patients over a nine-year period. The study population included adults with type 2 diabetes, moderate cardiovascular disease risk, no baseline advanced DR and minimum one year enrollment prior to GLP-1 treatment.  When comparing patients who initiated treatment with exenatide (n=14,076, median follow-up: 969 days), to those starting dulaglutide (n=54,787, median follow-up: 948 days) or liraglutide (n=25,562, median follow-up: 1,007 days), no differences were found in the hazard of composite treatment for diabetic macular edema (DME) and/or proliferative DR: exenatide vs. dulaglutide, liraglutide vs. dulaglutide or liraglutide vs. exenatide, nor were differences found in any comparisons for treatment of DME or PDR individually. Likewise, when comparing patients initiating semaglutide (n=30,911, median follow-up: 625 days) vs. dulaglutide (n=32,844, median follow-up: 639 days), the hazards for treatment of DME and/or proliferative DR, DME and proliferative DR all found no difference between drugs.“In the context of a shifting paradigm in type 2 diabetes management and the current limited understanding of the potential impact on retinal risk, it is encouraging that there were no inter-agent differences in retinopathy complications in this head-to-head comparison,” the study authors wrote in their paper. “These results will reassure patients and physicians caring for them,” and support doctors in choosing the most appropriate drug “without consideration of possible differences in the risk of retinopathy complications.”Click here for the journal source. Barkmeier AJ, Deng Y, Swarna KS, et al. Risk of sight-threatening diabetic retinopathy with GLP-1 RA use in routine clinical practice: comparative effectiveness of semaglutide, dulaglutide, liraglutide and exenatide. Ophthalmol Retina. August 5, 2025. [Epub ahead of print].  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.