Semaglutide and suicide risk, UniVr experts ‘caution and more studies’

The possible link between anti-diabetes weight-loss drugs such as semaglutide and the risk of suicide is back in the spotlight of science. A study published in ‘Jama Network open’ in which Corrado Barbui and Chiara Gastaldon from the University of Verona participated, as well as Georgios Schoretsanitis, a psychiatrist and researcher at Zucker Hillside Hospital in New York, USA. In light of the results of the study, the Italian authors call for caution and underline the need for new studies to clarify the causal link between these drugs and suicidal ideation. A cause-effect relationship, in fact, has not yet been proven.

Semaglutide, a Glp-1 receptor agonist, is also known in the news for the ‘celebrity’ patients who allegedly used it to lose weight quickly, from Elon Musk to Oprah Winfrey and Robbie Williams. The new research drew on the World Health Organization’s global database of suspected adverse drug reactions. Specifically – UniVr reports – the reports of adverse events involving suicidal thoughts, self-harm and suicidal/self-harm behaviors or attempts associated with semaglutide and liraglutide were analyzed, collected between November 2000 and August 2023. 107 cases of people with suicidal ideation linked to semaglutide and 162 linked to liraglutide were identified.

“A significant finding of the study – the researchers explain, according to the University of Verona – was that semaglutide is disproportionately associated with reports of suicidal ideation. This association remained statistically significant even when patients were taking other medications such as antidepressants or benzodiazepines, while it was not significant in people who were not taking antidepressants, suggesting a possible increased risk in people with depression or a history of depression as well as diabetes and obesity. Furthermore, the disproportion was significantly higher for semaglutide than for other antidiabetic drugs for type 2 diabetes and obesity such as dapagliflozin, metformin and orlistat. The study highlighted this increase in reports of suicidal ideation linked to semaglutide, but urgent further investigation is needed to clarify the potential risks and establish whether there is indeed a causal link in this correlation”, specify the experts who nevertheless consider the result of the work “particularly worrying given the widespread and expanding use of semaglutide both for the management of diabetes and for the management of obesity.”

“Based on these results – says Gastaldon, who coordinated the study of the Section of Psychiatry of the Department of Neuroscience, Biomedicine and Movement Sciences of the University of Verona – we suggest that doctors who prescribe semaglutide inform their patients about the risks of the drugs and evaluate the psychiatric history and mental state of patients before starting treatment with semaglutide, acting with caution, thoroughly evaluating risks and benefits in those who suffer from depression or have suffered from depression, suicidal ideation or suicide attempts”. Furthermore, “we encourage health professionals to monitor and advise patients who use semaglutide to report new or worsening depression, suicidal thoughts or any unusual changes in mood or behavior”.

“Future studies should take a closer look at the risk of suicidal ideation associated with semaglutide in people with a history of psychiatric disorders or in people with comorbid psychiatric disorders,” the expert continues. “Tirzepatide – he adds – a dual agonist of the GIP and GLP-1 receptors recently approved for the treatment of obesity, should also be monitored by healthcare professionals and pharmacovigilance experts. We discourage the use of this drug for purposes other than those for which it was authorized and without any medical supervision, as has happened in several countries.”

“Physicians and patients – Gastaldon points out however – should not interpret these results as evidence of a causal relationship between suicidal ideation and semaglutide, since pharmacovigilance studies cannot demonstrate this, but only show an association between the use of semaglutide and reports of suicidal ideation”. The ongoing research on semaglutide and suicide risk, they point out from UniVr, confirms “the importance of timely proactive post-marketing surveillance. Pharmacovigilance collects and analyzes cases of adverse events, providing a picture of drug safety in real life, where subjects may be exposed to a series of additional drugs and may have comorbidities (significant exclusion criteria of pre-marketing clinical studies).” Both the American drug agency FDA and the European EMA are continuing surveillance on the topic using various post-marketing data.