In patients with type 2 diabetes (T2D), once-weekly semaglutide significantly increased the risk of developing nonarteritic anterior ischemic optic neuropathy (NAION) compared to non-exposure, doubling the five-year hazard ratio (HR), though it was associated with improved glycaemic control and other cardiometabolic benefits.
Clinical Summary
Main Finding:
Once-weekly semaglutide was independently associated with a doubled risk of NAION over a five-year period. This risk persisted after adjusting for confounding factors, including glycaemic control, cardiovascular history, and use of other medications.
Clinical Relevance:
• The findings underscore a potential link between semaglutide and NAION, an untreatable and vision-impairing condition, warranting caution in patients at higher ocular or cardiovascular risk.
• The elevated NAION risk contrasts with semaglutide’s proven efficacy in improving HbA1c, weight loss, and cardiovascular outcomes, necessitating individualised patient assessments before treatment.
Study Overview:
• Type of Study: National, longitudinal cohort study.
• Sample Size & Population: 424,152 persons with T2D (106,454 exposed, 317,698 unexposed).
• Intervention Duration & Doses: Up to five years of observation; median time to NAION onset post-exposure: 22.2 months.
• Comparison: Non-semaglutide users; sensitivity analyses included SGLT2 inhibitors.
Outcomes:
• Primary Measure (NAION Incidence): Adjusted HR of 2.19 for semaglutide users (p < 0.001).
• Secondary Measure (Cardiometabolic Benefits): Improvements in HbA1c and weight management with semaglutide.
• Safety Profile: No clear temporal “high-risk” window for NAION onset; higher baseline HbA1c in semaglutide users.
Considerations:
• Limitations included the inability to assess smoking, BMI, and ophthalmic examination results, and reliance on registry data for diagnoses and prescription adherence.
• No causal relationship was established, but findings highlight an important safety signal for future pharmacovigilance and research.
Implications for Patient Care
From a clinical perspective, these findings necessitate a more cautious approach when prescribing semaglutide, particularly for patients with pre-existing ocular or cardiovascular risk factors. Routine ophthalmologic evaluations could be considered for patients initiating therapy, although the rarity of NAION may limit the feasibility of widespread screening.
For future practice, identifying high-risk subgroups—such as those with “disc-at-risk” anatomy or uncontrolled hypertension—will be critical. Moreover, clinicians must weigh the drug’s benefits against this potential risk, particularly in patients with alternative treatment options.
Reference:
Grauslund, J., et al. (2024). “Once-weekly semaglutide doubles the five-year risk of nonarteritic anterior ischemic optic neuropathy in a Danish cohort of 424,152 persons with type 2 diabetes.” International Journal of Retina and Vitreous, 10:97. doi:10.1186/s40942-024-00620-x
Disclosure:
This article summary on Hormone Insight was created with both human and AI assistance. It underwent expert review to ensure accuracy and clarity.
