Two leading ophthalmic organizations—the American Academy of Ophthalmology (AAO) and the North American Neuro-Ophthalmology Society (NANOS)—have weighed in on recent research tying the use of semaglutide to an increased risk for nonarteritic anterior ischemic optic neuropathy (NAION).
First up: Semaglutide.
We already dove into this FDA-approved drug last week, but for a quick refresh:
What it is: Semaglutide belongs to a class of medications referred to as glucagon-like peptide-1 (GLP-1) receptor agonists (RA).
- What these do: Essentially, they prompt the body to produce more insulin, reduce appetite, and initiate a feeling of fullness (leading to weight loss).
Next: Two popular semaglutide products (both manufactured by Novo Nordisk) on the U.S. market include:
Now the inevitable question: What spurred this research?
Since its initial approval in 2017, semaglutide has been found to worsen existing diabetic retinopathy (DR) in diabetic patients following a drop in their blood glucose (blood sugar control).
Other effects may include blurred vision and macular complications.
However: Providing diabetic patients undergo regular eye exams and keep their ophthalmologists updated on medication use, these symptoms are largely manageable for the majority of this demographic.
Nevertheless: The investigators of this recent study sought to explore the drug’s ocular effect even further.
Now the study.
Published in JAMA Ophthalmology, the retrospective, matched cohort study was conducted by Massachusetts Eye and Ear researchers among a total of 710 neuro-ophthalmic patients.
The purpose: To investigate the potential and suspected association between the use of semaglutide among diabetic patients with the risk for NAION.
See our coverage on this for the complete rundown.
Cut to the chase on those findings.
Overall, the investigators concluded that the prescribed use of semaglutide is indeed associated with an increased risk of developing NAION.
Most importantly: Survival analyses for both T2D and obese/overweight participants determined that NAION may have the greatest risk of developing within the first year of starting semaglutide prescription use.
Now what are the AAO and NANOS saying?
In light of these findings, the organizations released a joint statement on July 8 with four key stipulations:
- Given that the study was not able to show treatment caused by NAION (only identify a potential link between semaglutide and the disease), the “intriguing finding should inspire more research that will help clarify if semaglutide does cause NAION.”
- Note: This takeaway is on par with the study authors’ conclusions, in which they recommended future investigation into the association with one of the following criteria:
- Larger, retrospective, multicenter, population-based study
- Prospective, randomized clinical trial (RCT)
- Post-market analysis of all GLP-1 RA drugs
- Note: This takeaway is on par with the study authors’ conclusions, in which they recommended future investigation into the association with one of the following criteria:
What else?
The organizations also noted that this study was the first to report an association between semaglutide and NAION.
They further called out the following risk factors for NAION (aside from being diabetic or overweight):
- Heart disease
- History of heart attack
- High blood pressure
- Sleep apnea
Any limitations called out?
Indeed there were. The organizations stated that, as all study participants were seen at the same large eye hospital, it made it difficult “to determine if this association is true of all people taking semaglutide.”
- To note: This limitation was also observed by the study’s investigators.
The AAO/NANOS suggestion: A postmarket surveillance study (measuring semaglutide for its safety/effectiveness in patients) would be “helpful in determining if there is a connection between semaglutide and NAION.”
So what do they recommend for patients?
Ultimately: “At this time, we do not recommend that people stop taking semaglutide.”
They further added that, if a patient develops a sudden loss of vision while taking the GLP-1 RA, to immediately stop and contact their doctor.
The AAO and NANOS concluded that “The study offers no information about people who previously had NAION who then developed it again following a prescription of semaglutide.”
Now, looking beyond this study; didn’t the AAO already study this connection?
Good memory!
Just last year (November 2023), the organization unveiled real-world data (RWD) analyzing the potential link between semaglutide and the development of vision loss in T2D patients.
Go on …
Investigators sought to determine this potential cause and effect by using the AAO’s Intelligent Research in Sight (IRIS) Registry to examine data from:
- 48,000+ adults
- Aged 51 to 75
- Diagnosed with T2D
- Treated with an injectable semaglutide between 2013 and 2021.
And those findings?
You can read our full coverage, but here’s a preview:
- 2.2% of eyes with no or background DR experienced a worsening of DR
- 3.5% of eyes with early-stage (mild or moderate nonproliferative DR [NPDR]) disease illustrated a worsening of DR
- Nearly 60% of eyes with severe NPDR or PDR experienced DR improvement
So, what’s next for this semaglutide research?
Similar to the AAO’s previous conclusions last fall, the AAO and NANOS recommended further research into the drug’s ocular effects and its involvement in causing NAION.
Any progress on this additional research yet?
As we’ve previously reported, a prospective clinical trial—dubbed “FOCUS” (NCT03811561)— is examining the long-term effects of semaglutide and diabetic medication among T2D patients aged 18+.
Give me those details.
- The setup:
- Participants divided into two groups (semaglutide vs placebo) to receive a once-weekly subcutaneous injection in addition to their standard diabetes treatment
- The dosages for each group:
- 0.25 mg for 4 weeks, then increased to 0.5 mg for 4 weeks, then 1.0 mg once weekly up to 260 weeks
- The duration: 5 years
- The primary outcome measure:
- Percentage of participants with at least 3 steps Early Treatment Diabetic Retinopathy Study (ETDRS) subject level progression at Year 5
- See here for secondary endpoints.
- Percentage of participants with at least 3 steps Early Treatment Diabetic Retinopathy Study (ETDRS) subject level progression at Year 5
That study is expected to conclude in February 2027.