Can semaglutide (glucagon-like peptide-1 receptor agonist) affect vision?

Can Semaglutide Affect Vision?

Yes, semaglutide can affect vision, primarily through worsening diabetic retinopathy complications, particularly in patients with pre-existing retinopathy, and the risk appears related to rapid A1C reduction rather than a direct drug effect. 1

Primary Vision Risks

Diabetic Retinopathy Complications

• The FDA label explicitly warns that in a 2-year cardiovascular outcomes trial, diabetic retinopathy complications occurred more frequently with semaglutide (3.0%) compared to placebo (1.8%) 1

• The risk is substantially higher in patients with pre-existing diabetic retinopathy: 8.2% with semaglutide versus 5.2% with placebo in those with baseline retinopathy, compared to only 0.7% versus 0.4% in those without known retinopathy history 1

• The American Diabetes Association confirms that semaglutide, along with other GLP-1 receptor agonists (liraglutide, dulaglutide), has been associated with increased risk of rapidly worsening diabetic retinopathy in randomized trials 2

• The mechanism appears to be rapid improvement in glucose control causing temporary worsening of retinopathy, not a direct drug effect 2, 1

Non-Arteritic Anterior Ischemic Optic Neuropathy (NAION)

• Recent meta-analysis of 78 trials with 73,640 participants found semaglutide associated with significantly increased odds of NAION (OR 3.92,95% CI 1.02-15.02) 3

• However, the evidence remains insufficient for definitive conclusions, as trial sequential analysis indicated inadequate sample size to rule out alternative results 3

• Case reports describe NAION occurring within months of semaglutide initiation, particularly in patients with vascular risk factors 4

Critical Pre-Treatment Assessment

Before initiating semaglutide, you must obtain a comprehensive dilated ophthalmologic examination to document baseline retinopathy status 5, 6

• For type 2 diabetes patients, this eye examination should occur at the time of diabetes diagnosis regardless of semaglutide consideration 2

• Specifically assess for proliferative diabetic retinopathy, as this represents the highest-risk population 2, 5

• Document the presence of "crowded" optic discs using optical coherence tomography, as this anatomic feature may predispose to NAION 7

Risk Stratification Algorithm

Highest Risk (Use with Extreme Caution)

• Pre-existing proliferative diabetic retinopathy 2, 5
• History of any diabetic retinopathy with diabetes duration ≥10 years 8
• Age ≥60 years with any retinopathy 8
• Small, crowded optic discs on examination 7

Moderate Risk (Use with Standard Monitoring)

• Any non-proliferative diabetic retinopathy 1
• Diabetes duration ≥10 years without known retinopathy 8
• Multiple vascular risk factors (hypertension, hyperlipidemia) 4

Lower Risk (Standard Precautions)

• No diabetic retinopathy on baseline examination 1
• Diabetes duration <10 years 8
• Well-controlled blood pressure and lipids 2

Initiation Protocol to Minimize Risk

Start at the lowest dose (0.25 mg subcutaneously once weekly) and titrate slowly to minimize rapid glycemic changes 6

• Increase to 0.5 mg after 4 weeks, then 1.0 mg, then 1.7 mg as tolerated 6

• Avoid aggressive A1C reduction targets in patients with established retinopathy—the mechanism of retinopathy worsening is related to rapidity of glucose lowering 5, 7

• Consider reducing or holding insulin or sulfonylureas when initiating semaglutide to slow the rate of glycemic improvement 2

Monitoring Requirements During Treatment

For Patients WITHOUT Baseline Retinopathy

• Repeat dilated eye examination annually if glycemic control is stable 9
• Consider screening every 1-2 years if no retinopathy develops and A1C remains at goal 9

For Patients WITH Baseline Retinopathy

• Repeat dilated retinal examinations at least annually, or more frequently (every 6 months) if retinopathy is progressing 9, 5
• Monitor closely during the first 4-8 weeks after initiation when A1C reduction is most rapid 6
• If retinopathy progresses to sight-threatening stages, refer immediately to ophthalmology 9

Important Clinical Caveats

The Retinopathy Risk Is Likely Class Effect

• Meta-analysis showed no association between GLP-1 receptor agonists as a class and retinopathy per se, except through the association with average A1C reduction 2

• Large observational studies found semaglutide had similar or lower risk of proliferative diabetic retinopathy compared to other diabetes medications including other GLP-1 receptor agonists 10

Cardiovascular Benefits May Outweigh Risks

• The American College of Cardiology notes semaglutide's 13% reduction in major adverse cardiovascular events 5

• In patients with established cardiovascular disease, the mortality benefit may justify use even in those with retinopathy, provided close ophthalmologic monitoring is maintained 5

Optimize Other Risk Factors

• Implement strategies to reach blood pressure and lipid goals, as these independently reduce retinopathy risk 2

• Ensure adequate hydration and monitor for gastrointestinal symptoms that could lead to volume depletion and potentially worsen optic nerve perfusion 1

Documentation Requirements

• Document pre-treatment ophthalmologic assessment in the medical record 5

• Obtain informed consent discussion specifically addressing the risk of retinopathy worsening and potential NAION, particularly in high-risk patients 5

• Note that the FDA label requires monitoring for progression of diabetic retinopathy in patients with a history of this condition 1