GLP-1 Agonists Powerful Results, But What’s the Catch

Glucagon-like peptide-1 (GLP-1) receptor agonists, including semaglutide and tirzepatide, have transformed the treatment of type 2 diabetes and obesity. However, as their use grows, so do safety concerns.

Recent studies have linked semaglutide to a rare eye condition called non-arteritic anterior ischemic optic neuropathy (NAION). The DrugCard platform has also identified a new study investigating a potential connection between GLP-1 agonists and thyroid cancer.

These findings have sparked essential discussions in the pharmacovigilance community, highlighting the need for ongoing safety monitoring.

New Studies on Semaglutide and NAION Risk

The Danish Medicines Agency has requested the European Pharmacovigilance Risk Assessment Committee (PRAC) to assess two new register-based studies from the University of Southern Denmark (SDU). These studies suggest a potential increased risk of non-arteritic anterior ischemic optic neuropathy (NAION) in patients receiving GLP-1 agonist semaglutide. NAION is a rare condition affecting the small blood vessels at the front of the optic nerve, potentially leading to sudden vision loss and visual field defects. The SDU studies analyzed data from large patient registries: one reviewed records of 424,152 diabetic patients, including 106,454 treated with semaglutide. Another study, in collaboration with the Norwegian Institute of Public Health, examined 44,517 Danish and 16,860 Norwegian diabetic patients who received semaglutide between 2018 and 2024.

Regulatory Response and Safety Review

Over the past six months, the Danish Medicines Agency has closely monitored NAION as a possible adverse effect of semaglutide. As of December 10, 2024, 19 reported cases of NAION in Denmark, with the first case linked to semaglutide reported in July 2024. Although previous data were inconclusive, the new studies reinforce suspicions and warrant further investigation. In response, PRAC has initiated a safety review of semaglutide-containing medicines. The review is based on data from clinical trials, post-marketing surveillance, and mechanistic studies. Its goal is to determine whether the risk of NAION is elevated in patients taking semaglutide. It is important to note that patients with type 2 diabetes may already have an inherently higher risk of NAION, making causality assessment complex.

GLP-1 Agonists and Thyroid Cancer: A New Safety Concern?

While NAION has been a recent focus, another potential safety issue with GLP-1 receptor agonists is their possible link to thyroid cancer. The DrugCard platform has identified a new study investigating this association.

A disproportionality analysis of the FAERS database examined the connection between weight-loss medications and thyroid cancer. The results showed significant positive associations for GLP-1 receptor agonists:

Semaglutide: ROR = 7.61 (95% CI: 6.37-9.08)

Dulaglutide: ROR = 3.59 (95% CI: 3.03-4.27)

Liraglutide: ROR = 15.59 (95% CI: 13.94-17.44)

Tirzepatide: ROR = 2.09 (95% CI: 1.51-2.89)

In contrast, metformin showed a weak inverse association (ROR = 0.58, 95% CI: 0.36-0.93), and no significant links were found for other medications like topiramate, dapagliflozin, or insulin glargine.

These findings emphasize the need for further research and close safety monitoring. It is essential as GLP-1 agonists are increasingly used for weight loss beyond their original diabetes indication.

Balancing Benefits and Risks of GLP-1 Agonists

GLP-1 receptor agonists have provided life-changing benefits for many patients, improving glycemic control and facilitating weight loss. However, emerging safety concerns emphasize the importance of pharmacovigilance and post-marketing surveillance. The ongoing PRAC review and further independent studies will be crucial in determining the actual risk profile of these medications.

Healthcare professionals and patients should remain informed about potential risks while weighing the benefits of GLP-1 agonists. As new data emerge, regulatory agencies will play a key role in ensuring that safety measures align with the evolving evidence.

Conclusion

While GLP-1 receptor agonists have transformed diabetes and obesity management, recent safety signals regarding NAION and thyroid cancer necessitate careful evaluation. The pharmacovigilance community must continue to monitor and assess these risks to ensure patient safety. The coming months will be critical as PRAC reviews available data and determines whether regulatory actions are warranted.

Patients and healthcare providers should stay vigilant, report adverse effects, and make informed decisions based on the latest scientific evidence.