The European Medicines Agency (EMA) has asked some licensees of GLP-1 receptor agonists for evidence on associations with suicidal ideation and self-harm as part of a review. These medications include semaglutide, liraglutide, and semaglutide and are used to treat type 2 diabetes and control weight.
The review was initiated by the Icelandic Medicines Agency in July after reports of suicidal thoughts and self-harm in people using liraglutide and semaglutide. So far, authorities have recovered and analyzed around 150 reports of possible cases of self-harm and suicidal thoughts.
The EMA Pharmacovigilance Risk Assessment Committee has also reviewed the available evidence from clinical trials, post-marketing surveillance and published literature on reported cases of suicidal thoughts and self-harm when using GLP-1 receptor agonists.
These drugs can cross the blood-brain barrier, according to drug reports from manufacturers Novo Nordisk and Lilly submitted to the US Food and Drug Administration. That may explain its effectiveness in influencing hunger signals, but it could also increase the risk of neuropsychiatric side effects.
However, the EMA said that no conclusion could be drawn at this time about a causal association and that several issues still needed to be clarified. His committee has agreed on further lists of issues that companies must address. An EMA spokesperson told The BMJ that they had so far been unable to publish the results of their review 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 medications with different mechanisms of action than GLP-1 receptor agonists.
The drug rimonabant was withdrawn from Europe in 2008 after being linked to suicidal thoughts, and the weight-loss drug buproprion carries a black box warning in the United States about suicidal thoughts. Similarly, phentermine hydrochloride and topiramate carry a warning instructing patients to stop taking them if they experience suicidal thoughts.
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 related to semaglutide associated with “suicidal and self-harming behaviors.”
Since 2010, the MHRA has received reports of 20 suspected adverse drug reactions related to liraglutide which were associated with "suicidal and self-harm behaviour". While only a few of the reports mentioned the medical purpose of the drug, they included both type 2 diabetes and weight loss.
Alison Cave, the MHRA’s chief safety officer, said the agency would "carefully consider all available evidence and communicate any further advice to patients and healthcare professionals as appropriate."
