A meta-analysis examined the potential association between glucagon-like peptide-1 receptor agonists and the risk of nonarteritic anterior ischemic optic neuropathy.
The post hoc meta-analysis included 69 randomized controlled trials (RCTs) and studied semaglutide, liraglutide, dulaglutide, exenatide, and lixisenatide compared to placebo or active controls. The primary outcome was the incidence of ischemic optic neuropathy (NAION) as reported by investigators. Given the sample size, a statistically significant association was unlikely due to the rarity of NAION. Indeed, the calculated absolute risk increase was 2.6 cases per 100,000 patient-years for glucagon-like peptide-1 receptor agonists (GLP-1 RA) users.
“The use of GLP-1 RA is associated with a reduction of major cardiovascular events, with possible improvements of heart failure, and renal function,” the researchers wrote in their recent Diabetes, Obesity, and Metabolism article. In addition to an increased risk of worsening pre-existing diabetic retinopathy, another recent study reported “a more than 4-fold increase in risk for NAION.” While worsening of diabetic retinopathy could be a “consequence of a sudden and wide reduction of hyperglycemia” and increased risk of NAION could be a result of selection bias, the possible link between NAION, obesity, diabetes, and obstructive sleep apnea remains a concern among clinicians.
In this study, the investigators found the incidence rate of NAION in the GLP-1 RA group was 5.6 cases per 100,000 patient-years. In the comparator group, the rate was 3.0 cases per 100,000 patient-years. However, they did not find a significant difference in risk of NAION between GLP-1 RA users and comparators, and there was low heterogeneity across studies.
Eight cases of NAION were reported in GLP-1 RA users: 6 were associated with semaglutide, 1 case was associated with liraglutide, and the final case was associated with dulaglutide.
Despite these results, the researchers described, the number of NAION events may not have been sufficient to yield significant results. Possible underreporting of NAION events were also a factor because they were not an independently adjudicated event, nor were arteritic or non-arteritic NAION specified in the RCTs analyzed.
In short, additional research on the association between GLP-1 RAs and NAION, as well as the safety of GLP-1 RAs for obese or diabetic patients who “already have an increased baseline risk of NAION,” is needed.
A full list of author disclosures can be found in the published research
