Is a GLP-1 (Glucagon-like peptide-1) agonist safe for an uncontrolled diabetic patient with no eye exam in the past 3 years?

GLP-1 Agonist Safety in Uncontrolled Diabetics Without Recent Eye Exam

A GLP-1 agonist should NOT be initiated in an uncontrolled diabetic patient whose last eye exam was 3 years ago until a comprehensive dilated eye examination is performed to assess for diabetic retinopathy, particularly proliferative disease. 1

Critical Pre-Treatment Requirement

Patients must undergo appropriate, guideline-recommended eye examinations before starting GLP-1 agonist therapy if an examination has not been completed within the last 12 months. 1 This is not merely a suggestion but a specific safety recommendation from the American College of Cardiology based on the SUSTAIN-6 trial findings. 1

The 3-year gap in eye examinations is particularly concerning because:

• Type 2 diabetics should have had an initial dilated eye examination at the time of diabetes diagnosis, with subsequent annual exams if retinopathy is present. 1
• If no retinopathy is present and glycemic control is adequate, exams every 1-2 years may be acceptable, but 3 years exceeds this interval. 1
• In an uncontrolled diabetic, the likelihood of having developed or progressed retinopathy during this 3-year period is substantial. 1

Why This Matters: The Retinopathy Risk

GLP-1 agonists, particularly semaglutide, have been associated with increased risk of diabetic retinopathy complications in randomized trials. 1, 2 The mechanism is critical to understand:

The retinopathy worsening is hypothesized to be related to the rapid reduction in blood glucose and A1C, not necessarily a direct drug effect. 1 This means:

• Patients with poor baseline glycemic control (HbA1c >9%) are at higher risk. 2
• Patients with pre-existing proliferative diabetic retinopathy are at particularly high risk. 2, 3
• The rapid improvement in glycemia can cause initial worsening of retinopathy. 1, 3

Without knowing the current retinopathy status after 3 years, you cannot assess this risk or implement appropriate mitigation strategies.

The Clinical Algorithm

Step 1: Obtain Eye Examination FIRST

• Schedule comprehensive dilated eye examination by ophthalmologist or optometrist before prescribing any GLP-1 agonist. 1
• Document the retinopathy status: none, non-proliferative (mild, moderate, severe), or proliferative. 1
• Assess for diabetic macular edema. 1

Step 2: Risk Stratification Based on Eye Exam Results

If NO retinopathy or only mild non-proliferative retinopathy:

• GLP-1 agonist can be initiated with standard precautions. 2
• Start at lowest dose and titrate slowly to minimize rapid A1C reduction. 2
• Plan for annual eye exams going forward. 1

If moderate to severe non-proliferative retinopathy:

• GLP-1 agonist can be used but requires enhanced monitoring. 2
• Reduce concurrent insulin dose by 20% when starting GLP-1 agonist to slow glycemic improvement. 2
• If on sulfonylureas with well-controlled baseline HbA1c, reduce sulfonylurea dose by 50%. 2
• Consider more frequent ophthalmologic monitoring (every 6 months rather than annually). 2
• Avoid aggressive A1C reduction targets initially. 2

If proliferative diabetic retinopathy:

• Exercise extreme caution; consider alternative agents first (SGLT2 inhibitors for cardiovascular risk reduction). 2, 3
• If GLP-1 agonist is still deemed necessary, ensure ophthalmology is actively managing the proliferative disease. 2
• Implement all mitigation strategies: slow titration, insulin/sulfonylurea dose reduction, frequent monitoring. 2

Common Pitfalls to Avoid

Pitfall #1: Assuming the patient has no retinopathy because they have no visual symptoms. Diabetic retinopathy is often asymptomatic until advanced stages. 1 The 3-year gap means you have no current data.

Pitfall #2: Prioritizing the cardiovascular benefits without addressing retinopathy risk. While GLP-1 agonists reduce cardiovascular events by 13% 2, this benefit must be weighed against potential vision-threatening complications in high-risk patients. The eye exam allows you to make this risk-benefit assessment properly.

Pitfall #3: Initiating therapy with plans to "get the eye exam soon." The retinopathy complications can occur with rapid A1C reduction, which begins immediately upon starting therapy. 1 The eye exam must precede initiation.

Pitfall #4: Believing all GLP-1 agonists carry equal retinopathy risk. While liraglutide, semaglutide, and dulaglutide have all been associated with retinopathy worsening 1, 3, semaglutide showed the most pronounced signal in SUSTAIN-6. 1 However, the mechanism appears related to rapidity of glycemic improvement rather than drug-specific effects. 2, 3

Nuance in the Evidence

There is conflicting evidence on GLP-1 agonist retinopathy risk:

• Some real-world studies show GLP-1 agonists may actually be protective against diabetic retinopathy when accounting for longitudinal glycemic control. 4
• A 2024 study found no increased risk of vision-threatening diabetic retinopathy with GLP-1 agonists compared to other oral agents in patients with non-proliferative retinopathy. 5
• However, the FDA drug label for semaglutide specifically warns about diabetic retinopathy complications and recommends monitoring patients with a history of diabetic retinopathy. 6

The key distinction: The protective effects seen in some studies likely reflect better long-term glycemic control. The risk occurs specifically with rapid A1C reduction in patients with pre-existing retinopathy, particularly proliferative disease. 1, 2, 7 This is why knowing the baseline retinopathy status is essential.

Documentation Requirements

Document in the medical record:

• Pre-treatment ophthalmologic assessment results. 2
• Informed consent discussion about retinopathy risks, particularly if pre-existing retinopathy is present. 2
• Mitigation strategies implemented (dose titration plan, insulin/sulfonylurea adjustments). 2
• Follow-up ophthalmology monitoring plan. 2

Bottom Line

Do not prescribe a GLP-1 agonist to this patient until a current eye examination is obtained. 1 The 3-year gap in eye care combined with uncontrolled diabetes creates an unacceptable knowledge gap about retinopathy status, which directly impacts both the safety of initiating GLP-1 agonist therapy and the necessary risk mitigation strategies. Schedule the eye exam first, then proceed based on the findings using the algorithm above.