Do medications like liraglutide (glucagon-like peptide-1 receptor agonist) and semaglutide (glucagon-like peptide-1 receptor agonist) increase the risk of eye disease, particularly in patients with pre-existing diabetes (diabetes mellitus)?

From the Guidelines

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) like liraglutide and semaglutide may potentially increase the risk of diabetic retinopathy complications in some patients with pre-existing diabetes, particularly those with established diabetic retinopathy, as noted in a recent study 1. This risk appears to be associated with rapid improvement in blood glucose levels rather than a direct toxic effect of the medications themselves. When blood sugar levels improve quickly, it can cause temporary worsening of retinopathy, a phenomenon called "early worsening." Patients with poorly controlled diabetes who have existing retinopathy are at highest risk. If you have diabetes and are considering starting liraglutide or semaglutide, it's advisable to have a comprehensive eye examination before beginning treatment, especially if you have a history of diabetic retinopathy. During treatment initiation, more gradual dose escalation and blood glucose control may help minimize this risk. Regular eye examinations should be continued throughout treatment to monitor for any changes. The benefits of these medications for glycemic control and cardiovascular protection typically outweigh this potential risk for most patients, but individual risk assessment is important, as suggested by recent guidelines 1.

Some key points to consider:

• The risk of diabetic retinopathy complications is more pronounced in patients with a prior history of proliferative retinopathy, as seen with semaglutide 1.
• GLP-1 RAs are unlikely to cause hypoglycemia on their own but may increase the risk when used with insulin or insulin secretagogues 1.
• Patients should be advised to undergo appropriate, guideline-recommended eye examinations before starting therapy if an examination has not been completed within the last 12 months 1.
• The presence of retinopathy is not a contraindication to aspirin therapy for cardioprotection, as aspirin does not increase the risk of retinal hemorrhage 1.

Overall, while there is a potential increased risk of diabetic retinopathy complications with GLP-1 RAs, the benefits of these medications for patients with diabetes, particularly in terms of glycemic control and cardiovascular protection, generally outweigh this risk, as supported by the most recent evidence 1.

From the FDA Drug Label

5.3 Diabetic Retinopathy Complications In a 2-year trial involving patients with type 2 diabetes and high cardiovascular risk, more events of diabetic retinopathy complications occurred in patients treated with OZEMPIC (3.0%) compared to placebo (1. 8%). The absolute risk increase for diabetic retinopathy complications was larger among patients with a history of diabetic retinopathy at baseline (OZEMPIC 8.2%, placebo 5.2%) than among patients without a known history of diabetic retinopathy (OZEMPIC 0.7%, placebo 0. 4%).

Medications like semaglutide may increase the risk of eye disease, particularly diabetic retinopathy complications, in patients with pre-existing diabetes. Patients with a history of diabetic retinopathy should be monitored for progression of diabetic retinopathy 2. Rapid improvement in glucose control has been associated with a temporary worsening of diabetic retinopathy. Key points to consider:

• The risk of diabetic retinopathy complications is higher in patients with a history of diabetic retinopathy at baseline.
• Patients without a known history of diabetic retinopathy also have an increased risk, although it is lower compared to those with a history of the condition.
• Monitoring of patients with a history of diabetic retinopathy is necessary to assess the progression of the disease.

From the Research

Link with Increase Chances of Eye Disease

The relationship between medications like liraglutide and semaglutide (glucagon-like peptide-1 receptor agonists) and the risk of eye disease, particularly in patients with pre-existing diabetes, is complex. Key points to consider include:

• The SUSTAIN clinical trial program found a safety issue concerning the progression and worsening of diabetic retinopathy with semaglutide use 3.
• A meta-analysis of randomized controlled trials suggested that semaglutide was not associated with an increased risk of diabetic retinopathy overall, but subgroup analysis indicated a potential increased risk in older patients or those with longer diabetes duration 4.
• A critical review of the effects of newer-generation anti-diabetics on diabetic retinopathy found that most drugs in these classes are neutral to DR progression, but there may be subclass differences, including potential slight DR worsening with semaglutide 5.
• Research on glucagon-like peptide-1 receptor expression in the human eye has shown low expression in normal eyes and no expression in eyes with advanced stages of proliferative diabetic retinopathy 6.
• A case report described the resolution of proliferative diabetic retinopathy following treatment with semaglutide, suggesting a potential independent role for semaglutide in managing PDR 7.

Factors Influencing Eye Disease Risk

Several factors may influence the risk of eye disease in patients taking semaglutide, including:

• Patient age: Older patients may be at increased risk of diabetic retinopathy when taking semaglutide 4.
• Diabetes duration: Patients with longer diabetes duration may be at increased risk of diabetic retinopathy when taking semaglutide 4.
• Glycemic control: Rapid improvements in glycemic control, such as those seen with semaglutide, may be associated with an increased risk of diabetic retinopathy 3.
• Presence of pre-existing diabetic retinopathy: Patients with pre-existing diabetic retinopathy may be at increased risk of progression or worsening of the disease when taking semaglutide 3, 4.