Meta-analysis Probes Rare Potential Vision Risk From GLP-1s

TOPLINE:

Patients treated with glucagon-like peptide 1 receptor agonists (GLP-1 RAs) appear to have a very low incidence of nonarteritic anterior ischemic optic neuropathy (NAION) when appropriately prescribed for obesity or diabetes. 

METHODOLOGY:

• A retrospective observational study recently suggested that semaglutide treatment may be associated with more than a fourfold increase in the risk for NAION, a rare condition potentially leading to blindness that is more frequent in people with obesity and diabetes.
• To assess the risk for NAION in adult patients receiving GLP1-RAs for diabetes or obesity, researchers conducted this meta-analysis, which included 69 randomized controlled trials that lasted at least 12 months, compared GLP-1s to a placebo or an active comparator (control arm), and disclosed a complete list of serious adverse events.
• The analysis included 144,226 and 132,922 patient-years in the GLP1-RA and control arms, respectively, and the trials used liraglutide (23 trials), semaglutide (19 trials), exenatide (15 trials), dulaglutide (seven trials), and lixisenatide (one trial).
• Most trials (n = 52) enrolled patients with type 2 diabetes only, while 17 enrolled those with obesity; the median age and body mass index of these patients was 57 years and 32, respectively, with the median study duration being 56 weeks.
• The endpoint was the difference in the incidence of NAION, as reported by investigators as a serious adverse event.

TAKEAWAY:

• Of the 69 trials, only five reported cases of NAION — eight cases in the GLP-1 group and four in the control group; the remaining 64 trials did not report any case of NAION.
• Among the different GLP-1s, six cases were noted in those using semaglutide and one case each in those using liraglutide and dulaglutide.
• GLP-1 treatment was not associated with an increased risk for NAION (odds ratio, 1.53; 95% CI, 0.53-4.44; P = .43).
• The estimated absolute increase in the risk for NAION with GLP-1 therapy was 2.6 per 100,000 patient-years (but it was noted that an increase of 570 per 100,000 patient-years would have been needed to achieve 80% statistical power).

IN PRACTICE:

“A relevant increase of the relative risk for a very rare, although severe, condition does not modify the overall risk-benefit ratio of effective drugs, at least when appropriately prescribed,” the authors wrote. “At the same time, we should be aware that the inappropriate use of drugs for inducing weight loss in moderately overweight patients with low cardiovascular risk could be associated with rare but severe adverse effects, possibly including NAION,” they added.

SOURCE:

The study was led by Giovanni Antonio Silverii, MD, Experimental and Clinical Biomedical Sciences ‘Mario Serio’ Department, University of Florence, Florence, Italy. It was published online in Diabetes, Obesity and Metabolism.

LIMITATIONS: 

With such a rare condition, the clinical trial numbers are not yet sufficient to demonstrate an association or establish the safety of GLP-1s, especially for semaglutide, which was the treatment in most of the detected cases. Also, the possibility of underreporting NAION could not be excluded as it was not independently analyzed as an adverse event. Lastly, the trials did not specify whether the reported cases were arteritic or nonarteritic, which may have presented a challenging differential diagnosis for many ophthalmologists.

DISCLOSURES:

This research was performed as a part of the institutional activity of the researchers, without any specific funding. One author reported receiving consultancy and speaking fees from several pharmaceutical companies outside this study, as well as grants for the unit he directs.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.