Objective:

To investigate the association between glucagon-like peptide-1 receptor agonists (GLP-1s) and the risk of anterior ischemic optic neuropathy compared to sodium-glucose cotransporter-2 inhibitors (SGLT-2s) in patients with type 2 diabetes.

Approach:

• Study Design: A nationwide, register-based cohort study emulating a target trial using linked Swedish health and administrative registers from 2013 to 2024.
• Participants: 107,518 patients initiating GLP-1 receptor agonists compared with 185,898 patients initiating SGLT-2 inhibitors.
• Outcome Assessment: Anterior ischemic optic neuropathy identified through the national patient register.
• Statistical Analysis: Adjusted risks estimated at 1, 3, and 5 years using propensity score weighting to balance demographic characteristics, diabetes severity, comorbidities, drugs, health care use, and ophthalmic risk factors.

Key Findings:

• Anterior ischemic optic neuropathy occurred in 62 patients receiving GLP-1s and 64 patients receiving SGLT-2s.
• At 1 year, absolute risks were 0.04% for GLP-1s and 0.02% for SGLT-2s; at 5 years, 0.12% for GLP-1s and 0.07% for SGLT-2s.
• The primary analysis indicated a 78% higher likelihood of anterior ischemic optic neuropathy among GLP-1 users compared to SGLT-2 users.
• Differences in risk were substantially reduced in analyses restricted to patients receiving metformin.

Interpretation:

GLP-1 receptor agonist use may be associated with a higher relative risk of anterior ischemic optic neuropathy among patients with type 2 diabetes, but the very low absolute event rates and attenuation of the association in analyses accounting for diabetes severity suggest cautious interpretation.

Limitations:

• Residual confounding could not be excluded despite adjustments.
• Small number of anterior ischemic optic neuropathy events.
• Possible outcome misclassification.
• Limited ability to evaluate individual GLP-1 receptor agonists.
• Uncertain generalizability to patients using GLP-1s for obesity without diabetes.

Conclusion:

The findings suggest a potential association between GLP-1 receptor agonists and anterior ischemic optic neuropathy, but the low absolute risks and confounding factors warrant careful consideration.

Sources:

• Annals of Internal Medicine