Available evidence does not support a causal association between glucagon-like peptide-1 (GLP-1) receptor agonists and suicidal and self-injurious thoughts and actions, according to the European Medicine Agency (EMA)’s Pharmacovigilance Risk Assessment Committee (PRAC).
This conclusion follows a review into GLP-1 receptor agonists starting in July 2023 after receiving case reports from the Icelandic medicines agency of suicidal thoughts and thoughts of self-injury from people using liraglutide and semaglutide.
At the time, the EMA said it was ‘not yet clear whether the reported cases are linked to the medicines themselves or to the patients’ underlying conditions or other factors‘.
The PRAC review has since included the results of a recent real-world cohort study looking at the association of semaglutide with risk of suicidal ideation.
Based on a large database of electronic health records, it investigated the incidence of suicidal thoughts in patients with overweight and type 2 diabetes mellitus treated with semaglutide or other non-GLP-1 receptor agonist medicines for diabetes or overweight.
The study found no causal association between the use of semaglutide and suicidal thoughts.
The EMA conducted a separate study based on electronic health records. This examined the risk of suicide-related and self-injury-related events in people with type 2 diabetes mellitus and found no causal association between the use of GLP-1 receptor agonists and this risk.
The PRAC also considered additional data from the marketing authorisation holders for semaglutide (brand names Ozempic, Rybelsus and Wegovy), liraglutide (brand names Victoza and Saxenda), degludec/liraglutide (brand name Xultophy), exenatide (brand names Byetta and Bydureon), lixisenatide (brand name Lyxumia), glargine/lixisenatide (brand name Suliqua), and dulaglutide (brand name Trulicity).
After reviewing the available evidence from non-clinical studies, clinical trials, post-marketing surveillance data and the available studies the PRAC announced that no update to the product information is warranted.
It added that close monitoring by the marketing authorisation holders is required and any new evidence on the issue must be reported.
This mirrors a similar conclusion from the US FDA in January 2024, in which it stated: ‘Our preliminary evaluation has not found evidence that use of these medicines causes suicidal thoughts or actions.‘
