Semaglutide, known by brand names like Ozempic and Wegovy, is used for managing type 2 diabetes and aiding in weight loss. It functions by mimicking a hormone that regulates appetite and insulin, leading to better blood sugar control. Diabetic retinopathy is a frequent complication of diabetes, characterized by damage to the light-sensitive tissue at the back of the eye, the retina. The growing use of semaglutide has raised questions about a potential association between the medication and a worsening of this eye condition.
The Link Between Semaglutide and Retinopathy Complications
Initial concerns about semaglutide’s effect on diabetic retinopathy were driven by the SUSTAIN-6 clinical trial. This study evaluated the cardiovascular safety of semaglutide in individuals with type 2 diabetes at high risk for heart-related events. While the medication demonstrated cardiovascular benefits, an unexpected finding was a higher rate of retinopathy complications in the group receiving semaglutide compared to a placebo.
The “retinopathy complications” in the SUSTAIN-6 trial referred to specific, vision-threatening events. These included vitreous hemorrhage, which is bleeding into the gel-like substance that fills the eye, and the need for retinal photocoagulation, a laser treatment to seal leaking blood vessels. The trial data indicated a notable increase in risk for the semaglutide-treated participants, predominantly in patients who already had diabetic retinopathy when they entered the study.
Subsequent analyses and real-world data have provided a more nuanced picture. A large retrospective study using the IRIS Registry examined thousands of individuals on semaglutide and found that after two years, only a small percentage experienced worsening retinopathy. Other research has produced varied results, with some studies showing no relationship. The labeling for semaglutide products now includes a warning about this potential risk, encouraging a cautious approach for those with a history of eye disease.
Understanding the Impact of Rapid Blood Sugar Control
The leading explanation for the observed increase in retinopathy complications is not a direct harmful effect of semaglutide on the retina. It is thought to be related to a phenomenon known as “early worsening” of diabetic retinopathy. This condition is not exclusive to semaglutide; it has been documented for decades with other intensive diabetes treatments, including insulin, that lead to a fast and substantial decrease in blood glucose.
In an individual with chronically high blood sugar, the tiny blood vessels in the retina adapt to this hyperglycemic environment. When blood sugar levels are brought down very quickly, as can happen with potent medications like semaglutide, these adapted vessels can undergo stress. This rapid change can disrupt their stability, leading to increased leakage and temporary progression of the retinopathy.
The magnitude and speed of the reduction in HbA1c, a measure of average blood sugar over several months, appear to be directly related to the risk. Patients who start with poorly controlled diabetes and achieve near-normal glucose levels in a short period are the most susceptible. This physiological stress response explains why the risk is most pronounced in the initial phases of treatment.
A meta-analysis of studies on this class of drugs, known as GLP-1 receptor agonists, found that the association with retinopathy was linked to the average A1C reduction, not the drug itself. This reinforces the idea that the rapid correction of high blood sugar is the primary driver.
Who Is at a Higher Risk?
The risk of experiencing a worsening of diabetic retinopathy while taking semaglutide is not uniform across all patients. The most significant factor is the presence and severity of pre-existing diabetic retinopathy. Individuals who have already been diagnosed with the condition, particularly if it is more advanced, are the most vulnerable to the “early worsening” phenomenon when their blood sugar is rapidly lowered.
Another contributing factor is the duration of diabetes. Those who have lived with diabetes for a longer period may have a higher likelihood of experiencing this complication. This is because the cumulative effects of high blood sugar over many years have already made the retinal blood vessels more fragile.
Patients starting with very high HbA1c levels (e.g., above 9%) who then experience a sharp drop after beginning treatment are at an increased risk. The combination of these factors—pre-existing, severe retinopathy, long-standing diabetes, and a dramatic reduction in blood glucose—creates the highest-risk profile.
Eye Health and Monitoring on Semaglutide
Given the potential for early worsening of retinopathy, proactive eye health management is a recommendation for individuals starting semaglutide, especially those with known risk factors. A comprehensive dilated eye exam performed by an ophthalmologist or retina specialist is recommended before initiating the medication. This baseline examination establishes the health of the retina and can identify any pre-existing retinopathy.
Following the initial assessment, regular follow-up eye exams are advised. The frequency of these check-ups will depend on the individual’s specific situation, including the findings of the baseline exam and their overall diabetes management plan. Consistent monitoring allows the ophthalmologist to detect any changes in the retina early, enabling prompt intervention if the retinopathy shows signs of progression.
Open communication between the patient, the prescribing physician, and the ophthalmologist is fundamental. This collaborative approach ensures that the benefits of improved blood sugar control with semaglutide are weighed against the potential risks to eye health. For some high-risk patients, the prescribing doctor might opt for a more gradual dose escalation to lessen the speed of glucose reduction.