Study Reveals Increased Risk of Optic Nerve Damage with GLP-1 Drugs

A recent study published in JAMA Ophthalmology has revealed a concerning association between the use of glucagon-like peptide-1 (GLP-1) receptor agonists, particularly liraglutide, and an increased risk of developing nonarteritic anterior ischemic optic neuropathy (NAION) during the first year of treatment. The findings are especially significant for individuals without type 2 diabetes (T2D) or obesity, raising critical questions about the safety of these medications in broader populations.

This study, led by Pallavi Nagdeve, MPH, and Russell Griffin, PhD, from the University of Alabama at Birmingham, analyzed data from 65,612 patients diagnosed with NAION. These individuals were matched against 641,751 control participants based on age, insurance enrollment year, and history of T2D or obesity. Researchers categorized GLP-1 use by duration and frequency, assessing prescriptions for various agents including dulaglutide, liraglutide, semaglutide, and exenatide.

The results indicated that any use of GLP-1 agents was linked to a 19% increase in the odds of developing NAION within the first year of treatment (odds ratio [OR], 1.19; 95% CI, 1.02-1.39). Notably, patients using liraglutide faced an even greater risk, with an OR of 1.53 (95% CI, 1.18-1.98). Alarmingly, the risk was elevated to an OR of 2.03 (95% CI, 1.07-3.85) for individuals without T2D or obesity, and further increased to 2.32 (95% CI, 1.04-5.20) for liraglutide users in this group.

The significance of these findings is underscored by the increasing popularity of GLP-1 receptor agonists for weight management, as they are often prescribed off-label to individuals without obesity or T2D. According to Dr. Sarah Johnson, Professor of Ophthalmology at the University of California, San Francisco, "The implications of this study are profound, as they highlight a potential risk that may not have been fully understood, particularly in off-label prescribing scenarios."

The methodology employed in this case-control study has been critiqued for its reliance on standard diagnostic codes, which may have led to misclassification of other optic neuropathy cases as NAION. Additionally, the database used had limitations that could introduce bias, as noted in the study's acknowledgments of potential unknown factors influencing the reported associations.

Despite the limitations, the study prompts important considerations for healthcare providers. Dr. Maria Rodriguez, an endocrinologist at the Mayo Clinic, expressed concern regarding the implications for patient safety. "As we navigate the increasing use of GLP-1 medications, it is imperative that we remain vigilant regarding potential adverse effects, especially in populations that may be at greater risk."

Future research is essential to explore the reasons behind GLP-1 receptor agonist use among individuals without obesity or T2D and to clarify these associations further. Larger sample sizes and more comprehensive data collection methodologies will be crucial in establishing a definitive understanding of the risks involved.

This study adds to a growing body of literature questioning the safety profiles of GLP-1 medications. Health professionals are urged to consider these findings in the context of patient treatment plans, balancing the benefits of weight management against the potential for serious adverse effects.

In summary, while GLP-1 receptor agonists like liraglutide offer significant benefits in managing weight and diabetes, this study highlights a critical risk that warrants further investigation and careful consideration in clinical practice. The implications of these findings extend beyond individual patients, potentially influencing prescribing practices and public health policies around GLP-1 medications.