Can GLP1 (Glucagon-like peptide-1) receptor agonists, such as Victoza (liraglutide) or Ozempic (semaglutide), cause vision loss?

GLP-1 Receptor Agonists and Vision Loss

Key Recommendation

GLP-1 receptor agonists, particularly semaglutide, may increase the risk of diabetic retinopathy complications in patients with pre-existing diabetic retinopathy, but do not cause vision loss in patients without pre-existing eye disease.

Risk Assessment for Diabetic Retinopathy

The FDA label for semaglutide (Ozempic) explicitly warns about diabetic retinopathy complications:

• In a 2-year trial, more events of diabetic retinopathy complications occurred in patients treated with semaglutide (3.0%) compared to placebo (1.8%) 1
• The absolute risk increase was significantly higher among patients with a history of diabetic retinopathy at baseline (semaglutide 8.2%, placebo 5.2%) compared to those without (semaglutide 0.7%, placebo 0.4%) 1
• The mechanism is likely related to rapid improvement in glucose control, which has been associated with temporary worsening of diabetic retinopathy 1

Risk Stratification

The risk of retinopathy complications varies by:

1. Pre-existing retinopathy status:

   • High risk: Patients with established diabetic retinopathy
   • Low risk: Patients without pre-existing retinopathy

2. Specific GLP-1 agonist:

   • Higher risk: Semaglutide has the strongest association with retinopathy complications
   • Meta-analysis shows increased risk with parenteral semaglutide (relative risk = 1.73; 95% CI 1.10-2.71) 2

3. Magnitude of A1c reduction:

   • Higher risk: A1c decreases >1.0% are associated with increased retinopathy risk (RR = 1.59; 95% CI 1.092-2.316) 2
   • The risk appears to be related to rapid glycemic improvement rather than a direct drug effect

Management Recommendations

For Patients Without Diabetic Retinopathy:

• GLP-1 receptor agonists can be used with minimal concern for vision loss
• The number needed to harm (NNH) for the GLP-1 RA class is approximately 1000 2
• Regular eye examinations as recommended for all diabetes patients

For Patients With Established Diabetic Retinopathy:

1. Before starting therapy:

   • Obtain a baseline eye examination as recommended by guidelines 3
   • Consider ophthalmology consultation for patients with known proliferative retinopathy

2. During therapy:

   • Monitor for visual changes during treatment 1
   • Consider more gradual A1c reduction to minimize risk
   • Advise patients to promptly report any changes in vision 1

3. Patient education:

   • Inform patients about potential risk of diabetic retinopathy progression
   • Emphasize importance of regular ophthalmologic follow-up

Benefit-Risk Assessment

When considering GLP-1 RA therapy, weigh the following:

• Cardiovascular benefits: GLP-1 RAs reduce major adverse cardiovascular events (MACE) with a number needed to treat (NNT) of 77 for the class and 43 for semaglutide 2
• Retinopathy risk: For semaglutide, the NNH for worsening retinopathy is approximately 77 2
• Other benefits: Weight loss, renal protection, and improved glycemic control

Clinical Perspective

The 2018 American College of Cardiology expert consensus notes that an increased risk of diabetic retinopathy complications has been observed with semaglutide, predominantly in patients with prior history of proliferative retinopathy 3. This finding has not been consistently observed with other GLP-1 RAs.

Recent research suggests that while there may be an increased risk of early-stage retinopathy with some GLP-1 RAs compared to placebo, they may actually protect against late-stage diabetic retinopathy compared to insulin 4.

Conclusion

GLP-1 receptor agonists do not cause vision loss in patients without pre-existing eye disease. The risk of diabetic retinopathy complications is primarily in patients with established retinopathy and is likely related to rapid glycemic improvement. The cardiovascular and metabolic benefits of these medications generally outweigh the retinopathy risk for most patients, but careful monitoring is warranted in high-risk individuals.