European regulator finds no link between GLP-1 drugs and suicidal thoughts

The European Medicines Agency's safety committee concluded on April 12, 2024 that available evidence does not support a causal link between GLP-1 receptor agonists — including semaglutide — and suicidal or self-injurious thoughts and actions. The committee said no update to the medicines' product information is warranted ^[1].

The conclusion came from the agency's Pharmacovigilance Risk Assessment Committee, or PRAC, and covers dulaglutide, exenatide, liraglutide, lixisenatide and semaglutide ^[1]. In the United States, semaglutide is sold as Ozempic and Rybelsus for type 2 diabetes and as Wegovy for weight management; liraglutide is sold as Saxenda, dulaglutide as Trulicity and exenatide as Byetta ^[1][2].

The review began in July 2023, after case reports of suicidal thoughts and thoughts of self-injury in people using liraglutide and semaglutide medicines ^[1]. The Icelandic Medicines Agency flagged reports in people taking Saxenda and Ozempic, according to BioSpace ^[2]. In November 2023, PRAC asked the companies holding marketing authorizations for those products — a list that includes Ozempic, Rybelsus, Wegovy, Victoza, Saxenda, Xultophy, Byetta, Bydureon, Lyxumia, Suliqua and Trulicity — for additional data ^[1]. At a preliminary stage in December 2023, the committee said it could not draw a definitive conclusion and asked for further clarifications ^[2].

To reach its final position, PRAC reviewed non-clinical studies, clinical trials, post-marketing surveillance data and two studies based on electronic health records ^[1]. One study looked at the incidence of suicidal thoughts in patients with overweight or type 2 diabetes treated with semaglutide or with non-GLP-1 medicines for diabetes or overweight; it found no causal association with semaglutide ^[1]. The other, conducted by EMA, examined suicide-related and self-injury-related events in people with type 2 diabetes and did not support a causal association ^[1].

The first of those studies, published in Nature Medicine in January 2024, used electronic health record data from more than 240,000 patients who were overweight or had obesity and found that GLP-1 medications did not worsen suicidal ideation, BioSpace reported. That report said the study found GLP-1 drugs were associated with a significantly lower likelihood of suicidal thoughts, and that a separate analysis of records from nearly 1.6 million people with type 2 diabetes reached a similar conclusion ^[2]. EMA's announcement describes the studies as showing no causal association; it does not state that the drugs reduce suicidal thoughts ^[1].

Why it matters for patients

The decision means European regulators did not add a warning about suicidal thoughts or self-harm to GLP-1 product information, and PRAC said no update is warranted ^[1]. In the US, the Food and Drug Administration opened its own investigation in January 2024 and said a week later that a preliminary review found no evidence supporting such an association ^[2]. The sources do not say whether that FDA review has been completed or whether US labeling has changed.

PRAC said the companies that make the medicines will continue to monitor these events closely, including any new publications, and report new evidence in periodic safety update reports ^[1]. Because the review covered the drug class as a whole, the conclusion applies to the medicines named above rather than to one brand alone ^[1]. The sources do not explain why some people reported suicidal thoughts while taking these drugs. They also do not include guidance for patients who notice mood changes during treatment.

What happens next

No further PRAC review of this issue was announced, and no dates were given for the next round of safety reporting. The committee said it expects new evidence to arrive through the companies' routine pharmacovigilance reporting ^[1].

Separately, PRAC agreed on the content of a communication for healthcare professionals about new proposed tablet strengths of Rybelsus, the oral form of semaglutide, covering differences between the current and newly proposed formulations. That communication goes to EMA's human medicines committee, and would be sent to healthcare professionals in EU member states after the application is finalized and if that committee issues a positive opinion ^[1].