GLP-1 Receptor Agonists and Risk of Optic Nerve or Vision-Threatening Events in Patients With Type 2 Diabetes or Cardiometabolic Diseases: A Meta-analysis of Randomized Controlled Trials

BACKGROUND: Data concerning glucagon-like peptide 1 receptor agonists (GLP-1 RAs) on risk of ischemic optic neuropathy (ION) are conflicting. PURPOSE: We synthesize current evidence of GLP-1 RAs on risk of optic nerve or vision-threatening events from randomized controlled trials (RCTs) in patients with type 2 diabetes or cardiometabolic diseases. DATA SOURCE: A total of 83,288 participants with type 2 diabetes/cardiometabolic diseases from 20 published RCTs were analyzed following Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA). STUDY SELECTION: RCTs investigating GLP-1 RAs for type 2 diabetes/cardiometabolic disease populations and reported optic nerve or vision-related adverse events were assessed. DATA EXTRACTION: Primary outcome was a composite of optic nerve and/or vision-threatening serious adverse events, including ION, ocular ischemic syndrome, papilledema, blindness, blurred vision, visual impairment, and reduced visual acuity. Odds ratios (ORs) were derived. DATA SYNTHESIS: Type 2 diabetes occurred in 76.4% of participants. Over mean follow-up duration of 2.97 years (estimated cumulative exposure of 240,334 patient-years), GLP-1 RA use was not associated with increased risk of primary end point (OR 1.20, 95% CI 0.73-1.97, I2 = 0%). Prespecified individual adverse events, including ION (OR 1.50, 95% CI 0.49-4.63), and vision loss/disturbance events (OR 1.08, 95% CI 0.60-1.94) were not significantly associated with GLP-1 RA use. LIMITATIONS: RCTs reported vision-threatening events as adverse events rather than as prespecified outcomes. CONCLUSIONS: Based on a large number of patients who contributed to a meta-analysis of RCTs involving participants with type 2 diabetes and cardiometabolic disease, GLP-1 RAs were not associated with an increased risk of optic nerve/vision-threatening events.