The European Medicines Agency (EMA) has asked some licence holders of GLP-1 receptor agonists for evidence into associations with suicidal ideation and self-harm as part of a review. These drugs include Ozempic (semaglutide), Saxenda (liraglutide), and Wegovy (semaglutide) and are used to treat type 2 diabetes and in weight management.
The review was triggered by the Icelandic Medicines Agency in July after reports of suicidal thoughts and self-injury in people using liraglutide and semaglutide. The authorities have so far retrieved and analysed about 150 reports of possible cases of self-injury and suicidal thoughts.
The EMA’s Pharmacovigilance Risk Assessment Committee has also reviewed the available evidence from clinical trials, post-marketing surveillance, and the published literature on reported cases of suicidal thoughts and thoughts of self-harm when using GLP-1 receptor agonists.
These drugs can cross the blood-brain barrier, show pharmacology reports by the manufacturers Novo Nordisk and Lilly submitted to the US Food and Drug Administration. That may account for their effectiveness in influencing hunger signals, but it could also increase the risk of neuropsychiatric side effects.1
However, the EMA said that no conclusion could be drawn at this point on a causal association and that several issues still needed to be clarified. Its committee has agreed further lists of questions that the companies need to address. An EMA spokesperson told The BMJ that they were unable to release the results of their review so far or the questions they would like answered, as their processes were still ongoing.
Similar warnings
Suicidal thoughts have previously been linked to other weight loss drugs with different mechanisms of action from GLP-1 receptor agonists.
Sanofi’s drug Acomplia (rimonabant) was withdrawn from Europe in 2008 after being linked to suicidal thoughts, and the weight loss drug Contrave (buproprion) carries a black box warning in the US about suicidal thoughts.2 Similarly, Qsymia (phentermine hydrochloride and topiramate) carries a warning telling patients to stop taking it if they experience suicidal thoughts.3
The UK’s Medicines and Healthcare Products Regulatory Agency (MHRA) is also separately reviewing any link between GLP-1 receptor agonists and self-harm. From 2020 to December 2023 it received 26 suspected adverse drug reactions involving semaglutide associated with “suicidal and self-injurious behaviour.”
The agency approved Novo Nordisk’s Wegovy in 2021 for weight loss treatment, but the drug has not yet been launched in Britain. Ozempic, which also contains semaglutide, is licensed for type 2 diabetes and is used off label for weight loss.
Since 2010 the MHRA has received reports on 20 suspected adverse drug reactions involving liraglutide that were associated with “suicidal and self-injurious behaviour.” While only some of the reports mentioned the drug’s medical purpose, they included both type 2 diabetes and weight loss.
Alison Cave, MHRA chief safety officer, said that the agency would “carefully consider all available evidence and communicate any further advice to patients and healthcare professionals as appropriate.”