A recent publication in JAMA Ophthalmology has brought to light potential risks associated with the use of semaglutide, a medication often prescribed for managing type 2 diabetes (T2D) and obesity.
The study analysed data from a broad patient population. The findings suggest a significant association between semaglutide and the onset of non-arteritic anterior ischemic optic neuropathy (NAION) in both diabetic and overweight or obese patients.
Study Background
This large-scale observational study evaluated the health records of 16,827 patients who were examined at a neuro-ophthalmology clinic from December 1, 2017, to November 30, 2023. All individuals had been referred for various neuro-ophthalmological evaluations, and those with a prior diagnosis of NAION were rigorously excluded. This method ensured that the study accurately assessed the incidence of NAION in patients currently prescribed semaglutide, as compared to those taking non-GLP-1 receptor agonist (RA) medications.
Study Findings
Diabetic Cohort Analysis: Increased NAION Risk with Semaglutide
The research team analysed the incidence of NAION among patients using semaglutide compared to those on other treatments. Within the diabetic cohort, the occurrence of NAION over 36 months was markedly higher in the semaglutide group at 8.9% (95% CI, 4.5%-13.1%), compared to only 1.8% (95% CI, 0%-3.5%) in the group treated with non-GLP-1 RA medications. This data yielded a hazard ratio (HR) of 4.28, indicating a more than fourfold increase in risk, which is statistically significant (P < .001).
Impact on Overweight or Obese Cohorts: Higher NAION Incidence
In the subgroup of overweight or obese patients, those prescribed semaglutide experienced a 6.7% incidence of NAION, compared to merely 0.8% in the non-GLP-1 RA group. This result provided an even higher HR of 7.64, underlining a substantial risk elevation (P < .001).
Semaglutide and Ocular Health: Comparisons with Other Studies and Medications
The results align with previous concerns about semaglutide’s impact on ocular health, highlighted in trials such as the SUSTAIN-6 trial. Though the SUSTAIN-6 study primarily focused on cardiovascular outcomes of semaglutide treatment in diabetic patients, they inadvertently revealed the potential ocular side effects linked to increased risk of retinopathy. 3% of patients in the semaglutide group experienced retinopathy complications, whereas in the placebo group, the incidence was 1.8%, representing a significant 76% increase (P = .02).
Observations similar to those with semaglutide have been noted with other drugs in the same GLP-1 RA class, such as liraglutide, used in the LEADER trial. This trial noted a nonsignificant increase in retinopathy complications, emphasising the nuanced effects of these medications on diabetic patients’ ocular health.
The Role of HbA1c Reduction in Neuro-Ophthalmic Risks
Some researchers and medical professionals attribute the increased risk of neuro-ophthalmic conditions, such as retinopathy or NAION, to the HbA1c-lowering effect of GLP-1 RA drugs rather than the direct effect of the drugs themselves. Semaglutide, with its stronger HbA1c-lowering effect compared to other GLP-1 RA drugs, may exacerbate existing neuro-ophthalmic conditions more significantly.
Clinical Implications
These findings are particularly significant considering the increasing use of semaglutide in the treatment of chronic conditions such as type 2 diabetes and obesity. The study underscores the necessity for clinicians to monitor for potential neuro-ophthalmic side effects in patients using semaglutide, especially those who may already be at elevated risk for ocular issues.
Ongoing Research and Future Directions
While the recent study identified an association between semaglutide and a potential heightened risk of NAION, additional research is necessary to establish causality. The FOCUS Trial, initiated in 2019 and expected to conclude by 2027, is set to further explore these links. Interestingly, a separate study presented at the 2023 American Academy of Ophthalmology’s annual meeting suggests that semaglutide may not exacerbate retinopathy in most patients. In fact, approximately 60% of eyes with advanced disease (severe nonproliferative or proliferative diabetic retinopathy) experienced an improvement in their diabetic retinopathy. However, researchers have indicated that the study had its limitations including its retrospective observational design, lack of a control group, and a lack of pre- and post-initiation of semaglutide comparisons.
Conclusion and Recommendations: Balancing Treatment Benefits and Risks
As the medical community continues to assess the safety profile of semaglutide, particularly in populations vulnerable to ocular complications, this study emphasises the urgent need for comprehensive patient assessment and monitoring. Healthcare professionals should carefully consider these findings when prescribing semaglutide, particularly for patients with pre-existing ocular conditions or those at high risk of developing NAION. Additionally, they may consider lowering the dose, especially for patients with preexisting retinopathy, particularly if intravitreal therapy or laser photocoagulation has been required. It is advisable to encourage regular ocular health screenings for patients on semaglutide to monitor for any potential adverse effects. It is crucial to ensure that the benefits of medications like semaglutide are balanced against their potential risks.Through continued research and vigilant clinical practice, the aim is to safeguard the vision and overall health of patients navigating the complexities of diabetes and obesity.
References
- Hathaway, J. T., Shah, M. P., Hathaway, D. B., et al. (2024). Risk of nonarteritic anterior ischemic optic neuropathy in patients prescribed semaglutide. JAMA Ophthalmology. https://doi.org/10.1001/jamaophthalmol.2024.2296
- Sharma, A., Parachuri, N., Kumar, N., et al. (2022). Semaglutide and the risk of diabetic retinopathy—current perspective. Eye, 36(1), 10–11. https://doi.org/10.1038/s41433-021-01741-5
- Tucker, M. E. (2017, June 10). New SUSTAIN-6 data could explain retinopathy worsening. Medscape. https://www.medscape.com/viewarticle/881413
- Hutton, D. (2023, November 3). AAO 2023: Weight loss drug does not appear to worsen diabetic eye disease in most patients. Ophthalmology Times. https://www.ophthalmologytimes.com/view/weight-loss-drug-does-not-appear-to-worsen-diabetic-eye-disease-in-most-patients
