What are the recommendations for using Ozempic (semaglutide) in patients with pre-existing retinal disease, particularly diabetic retinopathy?

Ozempic (Semaglutide) Use in Patients with Pre-existing Retinal Disease

Patients with a history of diabetic retinopathy should be monitored closely for progression of retinopathy when using Ozempic (semaglutide), as it may increase the risk of diabetic retinopathy complications, particularly in those with pre-existing retinopathy. 1

Risk Assessment and Monitoring

FDA Warning and Risk Factors

The FDA label for Ozempic specifically warns about diabetic retinopathy complications. In a 2-year clinical 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%) 1. The risk was notably higher in patients with:

• Pre-existing diabetic retinopathy (Ozempic 8.2% vs placebo 5.2%)
• Compared to those without known retinopathy history (Ozempic 0.7% vs placebo 0.4%)

Mechanism of Risk

The increased risk appears to be associated with rapid improvement in glucose control, which has been historically linked to temporary worsening of diabetic retinopathy 1. This phenomenon is similar to what has been observed with intensive insulin therapy and is not necessarily specific to semaglutide itself.

Recommendations for Clinical Practice

Pre-Treatment Evaluation

1. Baseline Eye Examination: All patients with type 2 diabetes should have a comprehensive dilated eye examination by an ophthalmologist or optometrist before initiating Ozempic 2.

2. Risk Stratification:

   • High-risk patients: Those with pre-existing retinopathy, especially moderate to severe NPDR or PDR
   • Lower-risk patients: Those without retinopathy or with mild NPDR

Monitoring During Treatment

1. For Patients Without Retinopathy:

   • Annual dilated eye examinations 2
   • Consider more frequent monitoring if rapid glycemic improvement occurs

2. For Patients With Pre-existing Retinopathy:

   • More frequent monitoring is required 2
   • Consider examinations every 3-6 months, especially during the first year of treatment
   • Coordinate care with an ophthalmologist experienced in diabetic retinopathy management

3. Special Attention During Initial Treatment Phase:

   • The first 16 weeks appear to be a critical period when rapid HbA1c reduction may trigger retinopathy progression 3
   • Consider slower titration of Ozempic in patients with pre-existing retinopathy

Management of Specific Retinopathy Stages

1. Any Level of Macular Edema, Severe NPDR, or PDR:

   • Prompt referral to an ophthalmologist knowledgeable in diabetic retinopathy management 2
   • Consider delaying Ozempic initiation until retinopathy is stabilized with appropriate ophthalmologic treatment

2. Moderate NPDR:

   • Close monitoring by ophthalmology
   • Consider more gradual titration of Ozempic

Clinical Decision Algorithm

1. Before Starting Ozempic:

   • Assess retinopathy status through comprehensive eye examination
   • If severe NPDR or PDR is present, consider stabilizing retinopathy first
   • Discuss risks and benefits with patient

2. During Ozempic Treatment:

   • For patients with pre-existing retinopathy: Monitor every 3-6 months
   • For patients without retinopathy: Annual monitoring
   • If rapid HbA1c reduction occurs (>2% in 3 months): Consider more frequent eye examinations

3. If Retinopathy Worsens During Treatment:

   • Consider slowing Ozempic dose escalation
   • Ensure prompt ophthalmologic intervention
   • Do not discontinue Ozempic abruptly as this may worsen glycemic control

Special Considerations

Pregnancy Planning

Women with pre-existing diabetes who are planning pregnancy should have a comprehensive eye examination and be counseled about the risk of development or progression of diabetic retinopathy 2. This is particularly important if Ozempic is being used pre-conception.

Balancing Benefits and Risks

Despite the retinopathy concerns, it's important to note that for most patients, the benefits of improved glycemic control, weight loss, and cardiovascular risk reduction with Ozempic likely outweigh the potential retinal risks 4. The decision should be made with consideration of the individual's overall risk profile.

Emerging Evidence

Recent research suggests potentially conflicting effects of semaglutide on the retina:

• Some experimental studies suggest semaglutide may have direct beneficial effects on retinal neuroinflammation and vascular leakage 5
• There are isolated case reports of PDR resolution following semaglutide treatment 6

However, clinical trial data showing increased risk of retinopathy complications 1, 3 should take precedence in clinical decision-making until more definitive studies are available.