Researchers have found an apparent disproportional risk of suicidal thoughts with semaglutide compared with other diabetes drugs.
A study based on a World Health Organization global database of adverse drug reactions found while cases were very rare patients were significantly more likely to report suicidal thoughts while taking semaglutide compared to other medication.
The increased risk also remained significant when the researchers compared semaglutide with dapagliflozin and metformin and in the subgroup of patients with co-reported use of antidepressants and benzodiazepines.
In all there were 107 reports of suicidal ideation or self harm associated with semaglutide and 162 with liraglutide between 2000 and 2023. Only semaglutide was found to have a significantly disproportionate rate than what would be expected among adverse drug reactions.
Writing in JAMA Network Open the researchers said the ‘detected signal’ suggested more work was urgently needed to clarify any association.
Lead author Dr Georgios Schoretsanitis, a psychiatrist at the Zucker School of Medicine in New York, US, said a more cautious approach should be taken to in use of the drug in patients with existing psychiatric problems.
He wrote: ‘People with anxiety and depressive disorders may be at higher probability of reporting suicidal ideation when medicated with semaglutide.
‘Based on these findings, we believe that a precaution of use in patients with psychiatric disorders or psychological lability could be added in the semaglutide package insert.’
Semaglutide, under the brand Wegovy, was made available from the NHS for weight loss last year.
The RCGP has warned that unregulated online sales are posing a threat to patient safety and leading to shortages.
Experts urged caution in interpretation of the results which could not show causality and needed further investigation.
Dr Riccardo De Giorgi, clinical lecturer in the Department of Psychiatry at the University of Oxford, said there was currently no plausible biological explanation for a potential link between semaglutide and suicidal thoughts.
But he added, based on the findings: ‘A call for caution and for further investigations in these groups of people, including those with pre-existing psychiatric disorders such as depression, is probably justified.’
Dr Nerys Astbury, senior researcher in diet and obesity at Nuffield Department of Primary Health Care Sciences at the University of Oxford, said the disproportionality shown by the researcher suggests ‘further close investigation is needed to explore possible effects of GLP-1 agonists, now popular weight loss medications, on adverse mental health outcomes’.
‘Because of the inherent limitations of the data used in the study the authors only have data on suicidality in people who take semaglutide and they don’t know how many semaglutide users don’t have this reaction. For this reason they can’t say how likely this reaction is.’
She added that the authors reported the suicidal ideation only stopped in 63% of cases once use of the drug was discontinued, which further complicated the picture.
‘Whilst the findings reported here are observational, and cannot infer causality, they send a clear message that there is a lot still to be learnt about the newer classes of obesity mediations,’ Dr Astbury concluded.
In April, following a review into glucagon-like peptide-1 (GLP-1) receptor agonists, the European Medicine Agency’s Pharmacovigilance Risk Assessment Committee said that available evidence does not support a causal association between GLP-1 receptor agonists, such as semaglutide, and suicidal and self-injurious thoughts and actions.
Update: On 4 September 2024, the Medicines and Healthcare products Regulatory Agency (MHRA) ruled that available evidence does not establish a causal relationship between GLP-1 receptor agonists and suicidal behaviour, suicidal ideation, self-injury and depression.
Aligning with the results of EMA’s PRAC review, the MHRA review concluded that no updates to the product information of GLP-1 receptor agonists are warranted at this time.
A version of this article was originally published by our sister publication Pulse.
