Regulators in both the U.S. and Europe have looked into the potential link between suicidal thoughts and Novo Nordisk’s blockbuster semaglutide franchise after reports sounded the alarm last year. While the agencies found no increased risk for the popular diabetes and obesity drug, a new study could fuel the debate.
In a study recently published in the Journal of the American Medical Association (JAMA), researchers found a “significant disproportionality” for semaglutide-associated suicidal ideation compared with other medicines, particularly among patients who also use antidepressants.
No such link was found for Novo’s earlier-generation GLP-1 med, liraglutide, according to the team. The study was based on the World Health Organization's (WHO's) database of suspected suicidal and self-injurious adverse drug reactions.
Branded as Wegovy, Ozempic and Rybelsus, Novo’s semaglutide medicines—and their liraglutide counterparts Victoza and Saxenda—all fall under the GLP-1 umbrella.
The drug class has seen soaring popularity in recent years as its list of documented benefits has expanded, bringing on an onslaught of new patients. The JAMA study notably includes patients who potentially used the GLP-1 meds off-label, and the data also lacked other information that could potentially play a part in added mental distress, such as rapid changes of body weight or BMI.
More importantly, a higher rate of suicidal ideation does not mean a causal relationship.
In a series of reactions disseminated by Science Media Centre, an independent science information organization, several experts called into question the significance of the research. Multiple experts said the study's method of finding a statistical disproportionality between two groups does not prove causality.
"Signal detection studies in pharmacovigilance databases are good for generating hypotheses, but are not suitable for assessing whether there is a causal association between a drug and an outcome," Ian Douglas, professor of pharmacoepidemiology at the London School of Hygiene & Tropical Medicine, said in a statement.
Novo, for its part, flagged “several limitations” of the study and maintained that it will continue to work with the FDA and other regulators to monitor the safety of its GLP-1 products, a company representative said in an emailed statement.
“We stand behind the safety and efficacy of all of our GLP-1RA medicines when they are used as indicated and when taken under the care of a licensed healthcare professional,” the spokesperson said. “The known risks associated with use of these medicines are reflected in their current FDA- and EMA-approved product labeling.”
Last year, two cases of suicidal thoughts and one case of self-harm from patients in Iceland prompted an investigation from the European Medicines Agency (EMA). And 201 reports of suicidal thoughts received by the FDA from users of semaglutide or Eli Lilly’s rival tirzepatide sparked a U.S. probe. While both regulators are still monitoring reports and probing any potential link, neither has so far found evidence that these medicines causes suicidal thoughts or actions.
Still, the JAMA study authors assert that a “precaution of use” in patients with psychiatric disorders or psychological lability could be added to the semaglutide package insert. The FDA label on Novo’s Wegovy already includes a similar warning, the researchers pointed out.
Other studies, such as one published in the journal Nature Medicine, have backed the FDA and EMA’s conclusions. The Nature Medicine study found that in 1.8 million diabetes and obesity patients, those who used semaglutide were less likely to have suicidal thoughts than patients on other treatments.
The findings from the EMA, FDA and other independent researchers align with Novo’s trial data, “including large-scale outcomes trials and observational studies,” according to the company spokesperson.