Patients taking Novo Nordisk’s blockbuster GLP-1 drug appear to be more likely to harbor thoughts of suicide or self-harm, especially if they are already suffering from anxiety or depressive disorders, according to a new study.
Novo Nordisk’s blockbuster GLP-1 treatment semaglutide—sold as Ozempic for type 2 diabetes and Wegovy for obesity—appears to be associated with a higher risk of suicidal ideation versus other drugs, according to a new study that drew from the World Health Organization’s safety database.
The results, published Tuesday in JAMA Network Open, are based on the WHO’s repository which included 107 cases of suicidal and/or self-injurious drug reactions associated with semaglutide between November 2000 and August 2023. Novo’s other GLP-1 analog liragulitde—marketed as either Victoza or Saxenda—was also linked with 162 such adverse reactions during the same time frame.
However, the study found “significant disproportionality” of suicide or self-harm thoughts was observed only with semaglutide. This effect was much stronger in patients who were also taking antidepressants, in whom the risk of suicidal ideation was higher by nearly 4.5 times. People on benzodiazepine therapy were also four times more likely to harbor thoughts of suicide or self-harm.
“This study using the WHO database found a signal of semaglutide-associated suicidal ideation, which warrants urgent clarification,” the authors concluded.
In interpreting the findings, the study’s researchers suggested that patients who were also suffering from anxiety and depressive disorders “may be at a higher probability” of also developing suicidal or self-injurious thoughts when medicated with semaglutide.
Comparing Novo’s incretin therapy against other popular drugs, the JAMA study also found that semaglutide therapy carried a significantly higher risk of suicidal ideation than AstraZeneca’s SGLT2 inhibitor Farxiga (dapagliflozin) and metformin, a common medication used to control blood sugar levels. Semaglutide’s suicidality risk was also higher than the gastric lipase blocker orlistat.
“To our knowledge, no previous reports investigated the association between semaglutide and suicidal ideation using this database,” according to the authors. They used the WHO’s global individual case safety report database, which is the “largest pharmacovigilance archive worldwide” with more than 28 million reports of suspected adverse drug reactions from 140 countries.
At the same time, the researchers cautioned that “the results of this study should be interpreted in light of several limitations,” such as the potential for missing information and uncontrolled confounders. The authors also flagged the “inability to infer causality,” which indicates that the thoughts of suicide and self-harm cannot yet be directly attributed to semaglutide.
Tuesday’s study adds to a growing but conflicting body of evidence regarding the safety of semaglutide . In January 2024, the FDA launched a probe into semaglutide—as well as Eli Lilly’s competitor tirzepatide—for suspected risks of suicidal ideation, alopecia and aspiration. At the time, the regulator said that its Adverse Event Reporting System picked up these safety signals between July and September 2023.
A week later, the FDA announced that its investigation found no conclusive link between GLP-1 receptors and an increased risk of suicidal thoughts. A Nature Medicine study published in the same month echoed the FDA’s findings and failed to identify a significant risk of suicidal ideation associated with semaglutide.
The European Medicines Association came to a similar conclusion. The European regulator first looked into the suicidality risk of GLP-1 treatments in July 2023 and announced in April 2024 that it could not establish a significant link.
