Study of Potential Ozempic Suicide Link Stokes Safety Debate

A new study that found evidence of a higher rate of suicidal thoughts among patients taking Novo Nordisk A/S’s popular weight-loss and diabetes drugs is adding to a debate among doctors about the drugs’ safety.

The study published Tuesday in JAMA Network Open is the first to mine the World Health Organization’s global database of suspected drug side effects for reports of suicidal thinking in patients who have taken the drugs. It found a bigger proportion of such reports from patients who’d taken semaglutide, the drug Novo markets as Ozempic for diabetes and Wegovy for weight loss, than from those who took other medicines.

The US Food and Drug Administration said this year that a preliminary evaluation didn’t find evidence that use of drugs like Ozempic and Wegovy causes suicidal thoughts or actions. Still, the agency said it can’t rule out a small risk and is continuing to investigate. In April, the European Medicines Agency’s risk assessment committee found no added risk of suicide or self-harm for people taking the drugs.

The EMA and FDA findings line up with data from clinical trials, Novo Nordisk said in an e-mailed statement. The company said it will work with regulators to monitor the safety of the medicines, including surveillance of data from ongoing studies and real-world use.

WHO’s database lacks important information that would put the results in perspective, such as how long patients had been treated, the authors of the JAMA Network Open report acknowledged. The data might have been biased because it relied on self-reporting from patients and their doctors, they said.

Still, the study findings should prompt physicians to be more cautious about prescribing semaglutide to people with a history of depression or suicide attempts, Francesco Salvo, a pharmacologist at the University of Bordeaux, wrote in an editorial published alongside the results.

Other doctors called the evidence in the paper weak and inconclusive.

“It has major limitations,” said Stephen Evans, an emeritus professor of pharmacoepidemiology at the London School of Hygiene and Tropical Medicine, in a comment distributed by the Science Media Centre. Spontaneous reports from patients like those in the WHO database “are very subject to bias, including effects of media reporting,” Evans said.

In the study, the authors looked at more than 32 million reports of possible side effects to the WHO’s VigiBase, a database used to track potential dangers of drugs that have reached the market. Reports to the database of suicidal thoughts and behavior as linked to semaglutide were 45% higher than other treatments.

Such reports were higher than those linked to a group of other diabetes and weight-loss treatments. The difference was greatest among patients who were taking antidepressants along with semaglutide.

The findings don’t mean that Ozempic and Wegovy are dangerous or that they induce thoughts of suicide. For example, losing a large amount of weight alone may have an emotional impact, according to Stephen Burgess, group leader at the University of Cambridge’s MRC Biostatistics Unit.

“We need to understand whether these results represent a specific side-effect of these drugs, or an uncommon but tragic consequence of some individuals’ weight loss journey,” he said in remarks published by the Science Media Centre.