Risk of Diabetic Retinopathy with Ozempic (Semaglutide)
Ozempic (semaglutide) is associated with a higher risk of diabetic retinopathy complications (3.0%) compared to placebo (1.8%) in patients with type 2 diabetes and high cardiovascular risk, with the absolute risk increase being greater among those with pre-existing diabetic retinopathy (Ozempic 8.2% vs. placebo 5.2%). 1
Understanding the Risk
- The FDA label for Ozempic specifically warns about diabetic retinopathy complications, noting that the risk is particularly elevated in patients who already have a history of diabetic retinopathy at baseline 1
- For patients without a known history of diabetic retinopathy, the risk is lower but still present (Ozempic 0.7% vs. placebo 0.4%) 1
- Rapid improvement in glucose control with semaglutide has been associated with temporary worsening of diabetic retinopathy 1
- The long-term effect of semaglutide on diabetic retinopathy complications has not been thoroughly studied 1
Risk Factors for Diabetic Retinopathy
- Duration of diabetes is the strongest predictor for development and progression of retinopathy, regardless of medication used 2
- In type 1 diabetes, the prevalence of any retinopathy increases from 8% at 3 years to 80% at 15 years 2
- For type 2 diabetes patients over age 30, retinopathy develops in 40% of insulin users and 24% of non-insulin users with less than 5 years of diabetes, increasing to 84% and 53% respectively after 19 years 2
- Proliferative diabetic retinopathy (PDR) develops in 2% of type 2 patients with less than 5 years of diabetes and in 25% of patients with diabetes for 25+ years 2
Comparative Risk Between GLP-1 Receptor Agonists
- Recent research comparing semaglutide to dulaglutide found no significant difference in the risk of sight-threatening diabetic retinopathy (HR 0.88,95% CI 0.70-1.11) 3
- The same study found no significant differences between exenatide, dulaglutide, and liraglutide regarding risk of diabetic macular edema and/or proliferative diabetic retinopathy 3
- This suggests that the risk of retinopathy may be a class effect of GLP-1 receptor agonists rather than specific to semaglutide 3
Potential Mechanisms
- GLP-1 receptor expression is low in normal human eyes and was not detected in eyes with advanced stages of proliferative diabetic retinopathy 4
- The retinopathy complications may be related to rapid correction of hyperglycemia induced by semaglutide rather than a direct toxic effect of the drug 5
- Some researchers hypothesize that semaglutide-related retinopathy may result from changes in perfusion leading to venous dilation and congestion during relative hypoglycemia 6
Monitoring and Management
- Patients with a history of diabetic retinopathy should be monitored closely for progression of diabetic retinopathy when taking Ozempic 1
- Pre-treatment assessment for retinopathy is important but often overlooked in clinical practice - one study found only 1.8% of patients had appropriate checks for retinopathy history before starting semaglutide 7
- Regular dilated eye examinations are recommended for all patients with diabetes, but frequency may need to be increased for those taking semaglutide, especially with pre-existing retinopathy 2
Clinical Implications
- The risk of retinopathy complications should be weighed against the benefits of improved glycemic control with semaglutide 1
- Patients should be informed about the potential risk and symptoms of worsening retinopathy 1
- Slower titration of semaglutide may be considered in patients with established retinopathy to avoid rapid glucose fluctuations 5, 6
- Coordination between endocrinologists and ophthalmologists is essential for patients with diabetes starting semaglutide, particularly those with pre-existing retinopathy 2