The available evidence does not support a causal association between the Glucagon-Like Peptide-1 receptor agonists (GLP-1) – dulaglutide, exenatide, liraglutide, lixisenatide and semaglutide – and suicidal and self-injurious thoughts and actions, the Pharmacovigilance Risk Assessment Committee (PRAC) of the European Medicines Agency (EMA) has concluded.
The review was started in July 2023 following case reports of suicidal thoughts and thoughts of self-injury from people using liraglutide and semaglutide medicines. In November 2023 the committee requested additional data from the marketing authorisation holders for Ozempic, Rybelsus, Wegovy, Victoza, Saxenda, Xultophy, Byetta, Bydureon, Lyxumia, Suliqua and Trulicity.
Additionally, the committee analysed the results of a recent study (Wang, W., et al. Association of semaglutide with risk of suicidal ideation in a real-world cohort. Nat Med 30, 168–176 (2024)), based on a large database of electronic health records, which 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.
A second study conducted by the EMA (Association between exposure to GLP-1 receptor agonists and risk of suicide-related and self-injury-related events | HMA-EMA Catalogues of real-world data sources and studies (europa.eu)), based on electronic health records, which examined the risk of suicide-related and self-injury-related events in people with type 2 diabetes mellitus, did not support a causal association between the use of GLP-1 receptor agonists and this risk.
After reviewing the available evidence from non-clinical studies, clinical trials, post-marketing surveillance data and the available studies the PRAC considers that no update to the product information is warranted.
The marketing authorisation holders for these medicines will continue to monitor these events closely, including any new publications, as part of their pharmacovigilance activities and report any new evidence on this issue in their Periodic Safety Update Reports (PSURs).