New study on suicidal ideation risk for Novo's Ozempic fuels safety debate

Regulatory bodies in the United States and Europe have been examining the potential link between Novo Nordisk's semaglutide, a popular medication for diabetes and obesity, and suicidal thoughts. This scrutiny came after reports raised concerns about such risks last year. Although these agencies did not find an increased risk associated with semaglutide, a new study may intensify the ongoing debate.

The study, which was published in the Journal of the American Medical Association (JAMA), revealed a "significant disproportionality" regarding suicidal ideation linked to semaglutide compared to other drugs, particularly among patients who are also using antidepressants. Interestingly, no such association was observed for Novo Nordisk’s earlier medication, liraglutide. The research was based on data from the World Health Organization's (WHO's) database, which tracks suspected suicidal and self-injurious adverse drug reactions.

Semaglutide is marketed under different brand names such as Wegovy, Ozempic, and Rybelsus, while liraglutide is sold as Victoza and Saxenda. Both medications belong to the GLP-1 class of drugs, which have gained considerable popularity recently due to their expanding list of benefits, thereby attracting a new wave of patients. The JAMA study included patients who might have used these GLP-1 medications off-label. However, the data did not account for other factors that could contribute to mental distress, such as significant fluctuations in body weight or BMI.

It is crucial to note that a higher incidence of suicidal ideation does not necessarily indicate a causal relationship. Several experts have voiced skepticism about the study's findings. According to Ian Douglas, a professor of pharmacoepidemiology at the London School of Hygiene & Tropical Medicine, the methodology used to detect signals in pharmacovigilance databases is effective for generating hypotheses but insufficient for establishing causality.

Novo Nordisk acknowledged several limitations in the study and emphasized its commitment to working with regulatory agencies like the FDA to monitor the safety of its GLP-1 products. A company representative reiterated that Novo Nordisk stands by the safety and efficacy of its GLP-1 receptor agonist medicines when used as indicated and under the supervision of a healthcare professional. The known risks of these medications are reflected in their FDA- and EMA-approved labeling.

The European Medicines Agency (EMA) initiated an investigation last year after receiving two reports of suicidal thoughts and one case of self-harm from patients in Iceland. In the United States, 201 reports of suicidal thoughts from users of semaglutide or Eli Lilly’s rival drug, tirzepatide, prompted the FDA to launch a probe. Both regulatory bodies continue to monitor these reports and investigate any potential links, but neither has found conclusive evidence that these medications cause suicidal thoughts or actions.

Despite these concerns, the authors of the JAMA study suggest adding a precautionary note on the semaglutide package insert for patients with psychiatric disorders or psychological vulnerability. Currently, the FDA label for Novo’s Wegovy already includes a similar warning.

Other research, including a study published in Nature Medicine, supports the findings of the FDA and EMA. The Nature Medicine study, which included 1.8 million diabetes and obesity patients, found that those using semaglutide were less likely to experience suicidal thoughts compared to those on other treatments. These findings align with Novo Nordisk’s own clinical trial data and observational studies, as confirmed by the company spokesperson.