GLP-1 Receptor Agonists and Eye Disease Associations
GLP-1 receptor agonists (GLP-1 RAs) are primarily associated with diabetic retinopathy, with specific agents like liraglutide, semaglutide, and dulaglutide shown to increase the risk of rapidly worsening diabetic retinopathy in randomized trials. 1, 2
Primary Association: Diabetic Retinopathy
Mechanism and Risk
- The worsening of diabetic retinopathy with GLP-1 RAs appears to be related to rapid reduction in A1C levels rather than a direct effect of the medication itself 1, 2
- The risk is particularly elevated in patients with pre-existing diabetic retinopathy 3
- In the SUSTAIN-6 trial, semaglutide was specifically associated with an increase in diabetic retinopathy complications compared to placebo 1
- In a cardiovascular outcomes trial with dulaglutide, diabetic retinopathy complications occurred in 1.9% of patients treated with dulaglutide 1.5 mg versus 1.5% with placebo 3
Risk Stratification
- Patients with a history of diabetic retinopathy at baseline have significantly higher risk (dulaglutide 8.5% vs placebo 6.2%) compared to those without known history (dulaglutide 1% vs placebo 1%) 3
- Recent evidence suggests that while GLP-1 RAs may be associated with a modest increase in incident diabetic retinopathy, they may actually be associated with fewer sight-threatening complications in the long term 4
Monitoring and Management Recommendations
Baseline Assessment
- Retinopathy status should be assessed before initiating GLP-1 RA therapy 1, 2
- People with type 2 diabetes should have an initial dilated comprehensive eye examination at the time of diabetes diagnosis 1
- Adults with type 1 diabetes should have an initial dilated eye examination within 5 years after diabetes diagnosis 1
Ongoing Monitoring
- If no retinopathy is present and glycemia is well controlled, screening every 1-2 years may be considered 2
- If any level of diabetic retinopathy is present, dilated retinal examinations should be repeated at least annually 1, 2
- If retinopathy is progressing or sight-threatening, more frequent examinations are required 1, 2
- Patients with a history of diabetic retinopathy should be monitored closely for progression when starting GLP-1 RAs 3
Risk Mitigation Strategies
- Consider more gradual improvement in glycemic control in patients with established retinopathy to minimize the risk of worsening 2
- Optimize blood pressure and serum lipid control to reduce the risk or slow the progression of diabetic retinopathy 2
- For patients who develop diabetic retinopathy on one GLP-1 RA, switching to a different agent within the class with potentially lower risk for retinopathy complications may be beneficial 5
Recent Evidence on Long-term Outcomes
- Recent real-world studies have shown mixed results regarding GLP-1 RAs and retinopathy:
- Some studies suggest GLP-1 RA use may be associated with decreased risk of diabetic retinopathy (HR: 0.31,95% CI: 0.26-0.37) and diabetic macular edema (HR: 0.40,95% CI: 0.27-0.59) 6
- Other studies show a modest increase in incident diabetic retinopathy (HR: 1.07,95% CI: 1.03-1.11) but lower occurrence of serious complications like vitreous hemorrhages (HR: 0.74,95% CI: 0.68-0.80) and blindness (HR: 0.77,95% CI: 0.73-0.82) 4
- Some studies found no significant difference in progression to proliferative diabetic retinopathy or vision-threatening diabetic retinopathy with GLP-1 RA use 4, 7
Clinical Implications
- All patients with diabetes treated with GLP-1 RAs should undergo regular eye examinations, regardless of whether they have pre-existing diabetic retinopathy 4
- The benefits of GLP-1 RAs for glycemic control, weight management, and cardiovascular risk reduction must be balanced against the potential risk of worsening retinopathy, particularly in patients with pre-existing eye disease 1
- The initial worsening of retinopathy may be temporary, and long-term outcomes may actually show protective effects against sight-threatening complications 4