Why do GLP-1 (Glucagon-like peptide-1) medications cause loss of vision?

GLP-1 Receptor Agonists and Vision Loss Risk

GLP-1 receptor agonists can cause vision loss primarily through worsening of diabetic retinopathy, especially in patients with pre-existing retinopathy and when blood glucose levels are rapidly reduced. 1, 2

Mechanism of Vision Loss

The vision loss associated with GLP-1 receptor agonists is not believed to be a direct toxic effect of the medications, but rather occurs through several mechanisms:

1. Rapid A1C reduction: The primary mechanism appears to be rapid and marked reduction in blood glucose levels, which can temporarily worsen retinopathy 2

2. Pre-existing retinopathy risk: Patients with pre-existing diabetic retinopathy, particularly those with proliferative retinopathy, are at highest risk 2

3. Medication-specific risks: Semaglutide has been most strongly associated with retinopathy complications in clinical trials, specifically in the SUSTAIN-6 trial 2

Evidence from Clinical Studies

• In the SUSTAIN-6 trial, semaglutide was associated with an increased risk of diabetic retinopathy complications compared to placebo, primarily in patients with pre-existing proliferative retinopathy 1

• A meta-analysis of cardiovascular outcome studies showed no direct association between GLP-1 RAs and retinopathy except through the association with rapid A1C reduction 1

• Recent research indicates that while GLP-1 RAs may be associated with a modestly increased risk of incident diabetic retinopathy (HR 1.07), they may actually reduce the risk of serious complications like vitreous hemorrhage (HR 0.74), neovascular glaucoma (HR 0.78), and blindness (HR 0.77) in patients with pre-existing retinopathy 3

Risk Stratification and Management

High-Risk Patients

• Patients with pre-existing proliferative diabetic retinopathy
• Patients with poorly controlled diabetes who may experience rapid A1C reduction
• Patients with long-standing diabetes

Monitoring Recommendations

1. Before starting GLP-1 RA therapy:

   • Complete dilated eye examination by an ophthalmologist or optometrist 1, 2
   • Assessment of retinopathy status 1

2. During GLP-1 RA therapy:

   • Regular ophthalmological examinations as per standard diabetes care 2
   • More frequent monitoring for patients with pre-existing retinopathy 2
   • If retinopathy is present, dilated retinal examinations at least annually 2

Balancing Risks and Benefits

Despite the potential risk of retinopathy complications, the cardiovascular and metabolic benefits of GLP-1 RAs are substantial and should be considered in treatment decisions:

• The absolute risk of vision loss is low and should not preclude GLP-1 RA use in most patients 2
• In patients with pre-existing retinopathy, the risk-benefit ratio should be carefully evaluated 2
• Recent evidence suggests that GLP-1 RAs may actually reduce the risk of blindness in patients with pre-existing retinopathy 3

Practical Recommendations

1. Screen before treatment: Perform comprehensive eye examination before initiating GLP-1 RAs, especially in patients with long-standing diabetes 2

2. Consider gradual titration: In patients with pre-existing retinopathy, consider slower titration of GLP-1 RAs to avoid rapid glucose reduction 1

3. Educate patients: Inform patients about potential retinopathy risk and the importance of regular eye examinations 2

4. Regular monitoring: Ensure patients adhere to recommended eye examination schedules 1, 2

5. Special populations: Exercise particular caution in pregnant patients with diabetes, as pregnancy can aggravate retinopathy 1

By following these recommendations, clinicians can minimize the risk of vision loss while allowing patients to benefit from the significant cardiovascular and metabolic advantages of GLP-1 receptor agonists.