Is there an association between Glucagon-like peptide-1 (GLP-1) receptor agonists and retinal tears?

GLP-1 Receptor Agonists and Retinal Tears

There is no established association between GLP-1 receptor agonists and retinal tears specifically, though these medications have been associated with diabetic retinopathy progression in patients with pre-existing retinopathy. 1, 2

Current Evidence on GLP-1 RAs and Retinal Health

• GLP-1 receptor agonists (GLP-1 RAs) have been associated with worsening of diabetic retinopathy in some patients, particularly when there is rapid reduction in A1C levels rather than due to a direct effect of the medication itself 1
• Recent evidence shows no increased risk of developing vision-threatening diabetic retinopathy (VTDR), proliferative diabetic retinopathy (PDR), or diabetic macular edema (DME) among GLP-1 RA users compared to those on other oral anti-diabetic medications 3
• When comparing GLP-1 RAs to SGLT2 inhibitors, patients with pre-existing diabetic retinopathy showed a higher incidence of retinopathy progression events with GLP-1 RAs (subdistribution hazard ratio 1.50,95% CI 1.01-2.23) 2
• In patients without diabetic retinopathy at baseline, the risks of ocular outcomes were similar between GLP-1 RA and SGLT2 inhibitor groups 2

Risk Assessment and Monitoring

• Retinopathy status should be assessed when intensifying glucose-lowering therapies such as those using GLP-1 RAs 1
• Baseline eye examination is recommended 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
• More frequent monitoring is necessary when starting GLP-1 RAs in patients with established retinopathy 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
• In cases where retinopathy develops or worsens on injectable GLP-1 RAs, switching to oral semaglutide may be beneficial, as suggested by case reports 4

Clinical Implications

• While there is evidence of potential worsening of pre-existing diabetic retinopathy with GLP-1 RAs, there is no specific evidence linking these medications to retinal tears 1, 3
• A meta-analysis found no elevated risk of incidence of diabetic retinopathy linked to GLP-1 RAs compared to insulin, and GLP-1 RAs may actually offer potential advantages over insulin regarding the overall incidence of diabetic retinopathy 5
• The increased risk of diabetic retinopathy requiring treatment when comparing GLP-1 RAs to oral antidiabetic medications may be due to the transient progression associated with rapid decrease in HbA1c - a phenomenon not specific to GLP-1 RAs 5

Common Adverse Effects of GLP-1 RAs

• The most frequently reported adverse effects of GLP-1 receptor agonists are gastrointestinal, including nausea, vomiting, and diarrhea 6
• These adverse effects are dose-dependent and more frequent with short-acting than long-acting drugs 6
• Slow titration is helpful in increasing gastrointestinal tolerability 6
• Acute pancreatitis is a rare adverse effect that has been linked to the use of exenatide 6