PRAC April 2024 – PRAC finds no link between suicidal thoughts and thoughts of self-harm and GLP-1 receptor agonists and new safety information for HCPs on new Rybelsus tablets

date: 26/04/2024

During its April 2024 meeting, the Pharmacovigilance Risk Assessment Committee (PRAC) of the European Medicines Agency (EMA) has concluded that there is no available evidence supporting a link between GLP-1 receptor agonists and suicidal thoughts and thoughts of self-harm and advice to CHMP on new Rybelsus tablets.

GLP-1 receptor agonists and suicidal thoughts and thoughts of self-harm
The PRAC has concluded that 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 thoughts or thoughts of self-harm.

GLP-1 receptor agonists are used to treat type 2 diabetes and some are also authorised for weight management under certain conditions in adults who are obese or overweight. The review started in July 2023, following case reports of suicidal thoughts and thoughts of self-harm from people using liraglutide and semaglutide medicines, and in November 2023 the committee requested additional data from the marketing authorisation holders for these medicines, namely Ozempic, Rybelsus, Wegovy, Victoza, Saxenda, Xultophy, Byetta, Bydureon, Lyxumia, Suliqua and Trulicity.

Additionally, the committee analysed the results of a recent study*, 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. 

Another study was conducted by EMA , based on electronic health records, which examined the risk of suicidal thoughts and thoughts of self-harm in people with type 2 diabetes mellitus. The results 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).

The following medicines containing a GLP-1 receptor agonist, licensed for the treatment of type-2 diabetes, are on the market in Belgium:

  • medicines containing the active substance dulaglutide: Trulicity;
  • medicines with the active ingredient exanetide: Bydureon;
  • medicines with the active ingredient liraglutide: Victoza;
  • medicinal products with the active ingredient semaglutide: Ozempic and Rybelsus.

New safety information for healthcare professionals: advice to CHMP on new Rybelsus tablets (oral semaglutide)
Rybelsus is a medicine used to control blood glucose (sugar) levels in adults whose type 2 diabetes is not controlled well enough.

In the context of an ongoing application (line extension) to introduce new strengths of tablets for Rybelsus (oral semaglutide), PRAC was consulted on a proposed direct healthcare professional communication (DHPC) and communication plan for Rybelsus. The committee agreed on the content of the DHPC aiming at informing healthcare professionals on the differences between current and newly proposed formulations.

The agreed content of the DHPC will be forwarded to EMA’s human medicines committee (CHMP) for adoption. After finalisation of the line extension application and in case of a positive opinion at CHMP, the DHPC will be disseminated to healthcare professionals by the marketing authorisation holder, according to an agreed communication plan, and published on the medicines database.

More information is available on the EMA website.

 

*Wang, W., Volkow, N.D., Berger, N.A. et al. Association of semaglutide with risk of suicidal ideation in a real-world cohort. Nat Med 30, 168–176 (2024).

Last updated on 26/04/2024