A new observational study has found an increased risk of suicidal ideation among patients who take Novo Nordisk’s flagship weight loss drug semaglutide compared to other drugs, adding to a mixed bag of research on the relationship between suicidal thoughts and GLP-1 use.
The analysis of WHO adverse event data comes with a key caveat: The risk was more pronounced in patients who were also taking antidepressants. When the study excluded reports from patients taking both medications, there was not a disproportionate relationship between semaglutide and suicidal thoughts.
Researchers found that among the 107 reports of suicidal ideation and/or self-harm, semaglutide was associated with a 45% increase compared to other drugs reviewed. The results, published Tuesday in JAMA, found suicidal or self-injury adverse events made up 0.35% of all the side effects reported for semaglutide in the database.
Both US and European regulators have investigated the connection between the GLP-1 class of weight loss medications and suicidal ideation, saying for now that they’ve yet to identify a risk. But the FDA noted in its preliminary update at the beginning of this year that because of the small sample size, “we cannot definitively rule out that a small risk may exist; therefore, FDA is continuing to look into this issue.”
Study authors also specifically assessed suicidality data from liraglutide, one of Novo’s earlier-generation metabolic drugs. Semaglutide was compared to three other drugs that have been prescribed for similar indications: dapagliflozin (the active compound in Farxiga), metformin and orlistat.
Key sensitivity analyses underpinned the study’s overall finding. Namely, the risk of suicidal thoughts was more than four times higher in patients who were taking both antidepressants and semaglutide, but reporting was not disproportionate when those cases were excluded. A similarly high risk was also identified in patients taking benzodiazepines and semaglutide, and reporting remained disproportionate when those co-medication cases were removed.
Semaglutide use was associated with a higher risk of suicidal ideation compared to liraglutide, but neither of the two were associated with higher risks of suicide attempts. Liraglutide on its own was not associated with a higher risk of suicidal ideation. When compared to the other three drugs that are similarly prescribed, semaglutide was associated with a disproportionate rate of suicidal ideation.
Novo Nordisk pointed to limitations in the study, namely a lack of data on dosage and treatment duration, pre-existing suicidal ideation and substance abuse.
“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 company said in a statement.
Georgios Schoretsanitis, the paper’s lead author and a psychiatric researcher at Northwell Health in New York, did not respond to a request for comment.