Can Glucagon-like peptide-1 (GLP-1) receptor agonists cause vision loss?

GLP-1 Receptor Agonists and Vision Loss: Risk Assessment and Management

GLP-1 receptor agonists can cause worsening of diabetic retinopathy in patients with pre-existing retinopathy, particularly when blood glucose levels are rapidly reduced, but they do not cause vision loss in patients without pre-existing retinopathy. 1

Risk Assessment for Vision Loss with GLP-1 RAs

Established Risk Factors

• Pre-existing diabetic retinopathy: Highest risk population 1
• Rapid A1C reduction: Rapid glycemic improvement can paradoxically worsen retinopathy 2, 1
• Proliferative diabetic retinopathy: Particularly vulnerable to worsening 1
• Long-standing poor glycemic control: Increases risk when starting GLP-1 RAs 1

Evidence from Clinical Trials

In the SUSTAIN-6 trial, semaglutide was associated with an increase in diabetic retinopathy complications compared to placebo 2. This effect is hypothesized to be related to rapid reduction in blood glucose and A1C rather than a direct toxic effect of the medication 2.

Recent Research Findings

More recent studies show conflicting evidence:

• A 2024 study found no increased risk of progressing to vision-threatening diabetic retinopathy, proliferative diabetic retinopathy, or diabetic macular edema among GLP-1 RA users compared to controls 3
• A 2025 study showed GLP-1 RA use was associated with a modestly increased risk of incident diabetic retinopathy but fewer sight-threatening complications including blindness, even among those with pre-existing retinopathy 4
• Another 2025 study found GLP-1 RA use was actually associated with decreased risk of diabetic retinopathy, diabetic macular edema, and treatment-requiring retinopathy/macular edema 5

Management Recommendations

Before Starting GLP-1 RA Therapy

1. Baseline eye examination: All patients with diabetes should have a comprehensive dilated eye examination 1

   • Type 1 diabetes: Within 5 years of diagnosis 2
   • Type 2 diabetes: At time of diagnosis 2

2. Risk stratification:

   • Highest risk: Pre-existing proliferative diabetic retinopathy 1
   • High risk: Any diabetic retinopathy 1
   • Lower risk: No retinopathy 1

During GLP-1 RA Therapy

1. Monitoring schedule:

   • No retinopathy: Eye exams every 1-2 years if glycemic control is good 2
   • Any level of retinopathy: Annual dilated retinal examinations 2
   • Progressive or sight-threatening retinopathy: More frequent examinations 2

2. Dosing strategy:

   • Consider slower titration of GLP-1 RAs in patients with established retinopathy to minimize rapid glucose reduction 1
   • Monitor for retinopathy progression when intensifying glucose-lowering therapies 2

3. Patient education:

   • Advise patients to report any vision changes immediately 1
   • Explain the importance of regular eye examinations 1

Potential Mechanisms and Considerations

Mechanism of Retinopathy Worsening

The worsening of retinopathy with GLP-1 RAs appears to be related to rapid glycemic improvement rather than direct toxicity to the retina 2, 1. This phenomenon is similar to what has been observed with intensive insulin therapy.

Gastrointestinal Effects and Other Side Effects

While not directly related to vision loss, GLP-1 RAs commonly cause gastrointestinal side effects including:

• Nausea and vomiting
• Dyspepsia
• Diarrhea
• Gastrointestinal reflux
• Constipation 2

These side effects can be mitigated by gradual dose escalation and educating patients to reduce meal size 2.

Conclusion

While GLP-1 RAs may cause worsening of pre-existing diabetic retinopathy, particularly with rapid glucose reduction, they do not appear to cause vision loss in patients without retinopathy. The benefits of GLP-1 RAs for glycemic control, weight management, and cardiovascular risk reduction should be weighed against the potential risk of retinopathy progression in patients with pre-existing eye disease.