SAT-619 - A Case of Semaglutide Therapy and Diabetic Retinopathy Progression in A Patient with Stable Glycemic Control

Introduction
Diabetic retinopathy (DR) is a common microvascular complication of diabetes and a leading cause of vision loss in working-age adults. Prior reports suggest a possible association between GLP-1 receptor agonists (GLP-1RAs) and DR worsening. We present a case of DR progression following initiation of semaglutide therapy.

Case Description
A 69-year-old male with a history of cerebrovascular accident, peripheral arterial disease, and type 2 diabetes mellitus diagnosed in 2008, complicated by DR, presented for routine follow-up after recent initiation of weekly semaglutide. He was started on insulin six years earlier for an HbA1c of 12.3%, with sustained improvement to 6–8% several years later. Semaglutide 2 mg weekly was initiated to optimize glycemic control and for its cardiovascular benefits. The patient maintained stable blood glucose levels without a significant change in HbA1c. Shortly after initiation, ophthalmologic evaluation revealed accelerated progression of pre-existing DR. Semaglutide was subsequently discontinued due to concern for medication-associated retinopathy worsening. Following discontinuation, retinopathy progression stabilized, with no other clear precipitating factors identified.

Discussion
Although sustained glycemic improvement reduces the risk of DR, rapid HbA1c lowering can transiently worsen pre-existing disease, a phenomenon observed in settings such as pregnancy, bariatric surgery, and insulin initiation or intensification. Observational data suggest that reported DR worsening with GLP-1RA therapy occurs predominantly in patients with pre-existing disease. These patients often have long-standing diabetes, high baseline HbA1c levels, and insulin use, factors independently associated with advanced microvascular disease. This suggests that the observed association may be due to confounding rather than a direct drug effect. Supporting this, experimental studies in non-diabetic animal models have not demonstrated direct retinal toxicity from GLP-1RAs, including semaglutide and liraglutide. Our patient developed DR progression after semaglutide initiation despite stable glycemia, with stabilization after discontinuation. This temporal association raises the possibility of a drug-related effect in patients with high-risk features. While evidence remains insufficient to establish causality and findings are limited to semaglutide, this case highlights the need for further studies to clarify the relationship between GLP-1RA therapy and DR progression and how this should influence clinical care.

Conclusion
Given increasing GLP-1RA use and limited data on the effect on DR, clinicians should take a cautious, individualized approach in high-risk patients. Closer ophthalmologic follow-up and patient education may be warranted until further evidence clarifies the nature of this drug-related association.

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