Data on weight loss jab link to suicidal thoughts needs ‘urgent clarification’

Data that suggests a weight loss jab may be linked to people having suicidal thoughts needs urgent clarification, experts have said.

According to a new study, figures from a World Health Organisation (Who) database suggest a bigger proportion of reports about the drug semaglutide (Wegovy) mentioned suicidal thoughts.

This is when compared to liraglutide (another weight loss drug, also known as Saxenda).

This was particularly the case among patients who also reported taking antidepressants, the study found.

The researchers of the study, published in Jama Network Open, say the findings warrant “urgent clarification”.

Writing in the journal, corresponding author Georgios Schoretsanitis, from Zucker Hillside Hospital, USA, and colleagues, said: “This study using the WHO database found a signal of semaglutide-associated suicidal ideation, which warrants urgent clarification.”

There were 30,527 adverse drug reactions to semaglutide reported to the WHO database between November 2000 and August 2023. Of these, 107 (0.35%) were reports of suicidal thoughts or self-harm.

And for liraglutide, there were 162 such reports out of 52, 131 total reports (0.31%).

But some academics suggest the evidence of the link between semaglutide and suicidal thoughts is “weak”.

Ian Douglas, professor of pharmacoepdidemiology, London School of Hygiene and Tropical Medicine, said: “This paper presents, at best, weak evidence of an association between semaglutide and suicidality.”

He added: “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.

“This means that whatever this study had found, it would not improve our understanding of GLP-1 agonists and the risk of suicidal behaviour.”

Stephen Evans, emeritus professor of pharmacoepidemiology, London School of Hygiene and Tropical Medicine, said the paper has major limitations.

He added: “This paper is based just on spontaneous reports which are sent to regulatory authorities in the country of the person reporting a suspected adverse reaction.”

Prof Evans said: “The evidence is extremely weak for a genuine effect in this instance.”

He continues “We can’t conclude from the study by Schoretsanitis et al that semaglutide itself is responsible for suicidality.

“There are other grounds, based on previous evidence and with other drugs, for being cautious in the use of semaglutide, and being aware of patients’ mental health when prescribing it is sensible, even though semaglutide itself seems not to increase mental health problems.”

Other experts suggest the research may be mixing up the effects of the weight loss jab, with the overall negative mental health consequences of weight loss potentially not bringing happiness for people who may expect it to.

Dr Stephen Burgess, group leader at the MRC Biostatistics Unit, University of Cambridge, said: “There are biological effects of the mechanism of action of these drugs.  And there is the wider impact of losing as much as 20% of one’s bodyweight, as has been seen in trials of these drugs.

“This is a life-changing intervention that will have largely positive consequences for many.

“But for others, the impact of losing a large amount of weight could have negative emotional consequences.

“If an individual thinks that losing weight is the key to happiness, but losing weight does not bring happiness, could this lead to depression and suicidal ideation?

“And if it did, would we say that GLP-1R agonists caused suicidal thoughts?

“While any mechanism that increases suicide risk demands action, these two potential causal pathways require different management.

“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.”

The study used data from a large WHO database, called VigiBase, of reports of adverse reactions to drugs from 140 countries.

Kevin McConway, emeritus professor of applied statistics, Open University, said: “The use of this system is an excellent, and relatively rapid, way to be vigilant about possible adverse reactions that arise after drugs are marketed.

“But, really, data from such a system can’t by any means establish everything we would want to know about adverse reactions to a drug.  That needs further investigation.”