What are the potential eye side effects of GLP-1 (Glucagon-like peptide-1) receptor agonists, such as liraglutide (Victoza) and semaglutide (Ozempic)?

Eye Side Effects of GLP-1 Receptor Agonists

GLP-1 receptor agonists can cause diabetic retinopathy complications, particularly in patients with pre-existing diabetic retinopathy, due to rapid glucose reduction. 1, 2

Primary Ocular Concern: Diabetic Retinopathy

GLP-1 receptor agonists have been associated with specific eye-related side effects, with diabetic retinopathy complications being the most significant concern:

• Diabetic retinopathy complications: In the SUSTAIN-6 trial, semaglutide was associated with an increased risk of diabetic retinopathy complications (3.0%) compared to placebo (1.8%) 1, 2

  • The risk was substantially higher in patients with pre-existing diabetic retinopathy (semaglutide 8.2% vs. placebo 5.2%)
  • Patients without pre-existing diabetic retinopathy had a much lower risk (semaglutide 0.7% vs. placebo 0.4%)

• Mechanism: The worsening of diabetic retinopathy is hypothesized to be related to rapid reduction in blood glucose and HbA1c levels rather than a direct toxic effect of the medication 1, 2, 3

Recommended Monitoring

Based on the evidence, the following monitoring is recommended:

• Baseline eye examination: Patients should undergo appropriate guideline-recommended eye examinations before starting GLP-1 receptor agonist therapy if an examination has not been completed within the last 12 months 1

• Increased vigilance: Patients with a history of diabetic retinopathy should be monitored more closely for progression of diabetic retinopathy 2

Other Potential Ocular Effects

Recent research has identified additional potential ocular effects of GLP-1 receptor agonists:

• Nonarteritic ischemic optic neuropathy (NAION): Some evidence suggests a possible association, though the mechanism remains unclear 3

• Potentially protective effects: Some studies suggest GLP-1 receptor agonists may have protective effects against:

  • Glaucoma 3
  • Age-related macular degeneration 3
  • Dry eye disease 3, 4
  • Superficial keratitis 4

• Neuroprotective effects: Experimental studies suggest GLP-1 receptor agonists may have neuroprotective effects in the retina, potentially through reduction of extracellular glutamate and activation of prosurvival signaling pathways 5

Risk Stratification

The risk of diabetic retinopathy complications appears to be stratified based on:

1. Pre-existing diabetic retinopathy: Highest risk group
2. Rapid HbA1c reduction: Patients experiencing rapid improvement in glycemic control
3. No history of diabetic retinopathy: Lowest risk group

Clinical Approach

When prescribing GLP-1 receptor agonists:

1. Screen for pre-existing diabetic retinopathy before initiating therapy
2. Consider more gradual dose titration in patients with pre-existing diabetic retinopathy to avoid rapid glucose reduction
3. Ensure regular ophthalmologic follow-up for patients with pre-existing diabetic retinopathy
4. Educate patients about potential eye symptoms that should prompt medical attention

Conclusion

While GLP-1 receptor agonists offer significant benefits for glycemic control, weight management, and cardiovascular risk reduction, clinicians should be aware of the potential for diabetic retinopathy complications, particularly in high-risk patients. Regular ophthalmologic monitoring is essential, especially for those with pre-existing diabetic retinopathy.