How does GLP-1 (Glucagon-like peptide-1) affect eyesight in individuals with diabetes?

GLP-1 Receptor Agonists and Eyesight in Diabetes

GLP-1 receptor agonists (GLP-1 RAs) may cause initial worsening of diabetic retinopathy, particularly when they lead to rapid reductions in A1C levels, necessitating careful retinopathy screening before initiating therapy and during treatment. 1

Effects of GLP-1 RAs on Diabetic Retinopathy

Risk of Retinopathy Worsening

• GLP-1 RAs including liraglutide, semaglutide, and dulaglutide have been shown to be associated with a risk of mildly worsening diabetic retinopathy in randomized trials 1
• The FDA label for semaglutide specifically lists diabetic retinopathy complications as a warning, noting that it "has been reported in a clinical trial" and that "patients with a history of diabetic retinopathy should be monitored" 2
• The worsening of retinopathy appears to be related to the rapid reduction in A1C levels rather than a direct effect of the medication itself 1

Mechanism of Effect

• The association between GLP-1 RAs and retinopathy is primarily through the rapid correction of hyperglycemia, which can temporarily worsen retinopathy 3
• Meta-analyses have shown no direct association between GLP-1 RA treatment and retinopathy per se, except through the association with average A1C reduction at the 3-month and 1-year follow-up 1

Comparative Risk

• When compared to insulin, GLP-1 RAs may be associated with a decreased risk of diabetic retinopathy (HR 0.67,95% CI 0.51-0.90) 4
• Compared to oral antidiabetic drugs, GLP-1 RAs have not shown an increased risk of incident diabetic retinopathy overall (HR 1.00,95% CI 0.85-1.17) 4
• Some research suggests that specific GLP-1 RAs may have different effects - for example, albiglutide has been associated with higher risk of early-stage DR compared to placebo but lower risk of late-stage DR compared to insulin 5

Clinical Recommendations

Screening Before and During Treatment

• Retinopathy status should be assessed when intensifying glucose-lowering therapies such as those using GLP-1 RAs 1
• Adults with type 1 diabetes should have an initial dilated eye examination within 5 years after diabetes diagnosis 1
• People with type 2 diabetes should have an initial dilated eye examination at the time of diabetes diagnosis 1
• If retinopathy is present, more frequent monitoring is necessary when starting GLP-1 RAs 1

Risk Mitigation Strategies

• Consider more gradual improvement in glycemic control in patients with established retinopathy to minimize the risk of worsening 1
• Optimize blood pressure and serum lipid control to reduce the risk or slow the progression of diabetic retinopathy 1
• Regular ophthalmologic follow-up is important in patients considered at higher risk of ocular adverse events when using GLP-1 RAs 3

Important Considerations and Caveats

• The long-term impact of improved glycemic control with GLP-1 RAs on retinopathy has not been well-studied in clinical trials specifically designed to assess this outcome 1
• Further data from clinical studies with longer follow-up purposefully designed for diabetic retinopathy risk assessment, particularly including individuals with established diabetic retinopathy, are needed 1
• Despite concerns about retinopathy, GLP-1 RAs have significant benefits for glycemic control, weight management, and cardiovascular outcomes that must be weighed against the potential retinopathy risk 3
• Some research suggests GLP-1 RAs may actually have protective effects on the blood-retinal barrier through specific signaling pathways, though more research is needed 6

Monitoring Protocol for Patients on GLP-1 RAs

• Baseline eye examination before starting GLP-1 RA therapy 1
• If no retinopathy is present and glycemia is well controlled, screening every 1-2 years may be considered 1
• If any level of diabetic retinopathy is present, dilated retinal examinations should be repeated at least annually 1
• If retinopathy is progressing or sight-threatening, more frequent examinations by an ophthalmologist are required 1