GLP1 agonists: FDA investigates suicide risk

It is rare for the US Food and Drug Administration (FDA) to act more slowly than its European counterpart, the EMA. However, this is the case with the diabetes and obesity blockbusters semaglutide (Novo Nordisk) and tirzepatide (Eli Lilly). Back in July, the EMA’s PRAC Committee launched an investigation into whether the highly sought-after drugs should carry a corresponding warning on the package leaflet following the frequent occurrence of “suicidal thoughts” after treatment with so-called GLP-1 agonists. This should actually be completed by the end of 2023 after the inclusion of additional drugs. However, despite the provisional all-clear that the current data situation does not permit a decision, the PRAC committee has further questions, meaning that the announcement of the result has been postponed until April 2024. The investigation concerns the preparations Ozempic, Rybelsus, Saxenda, Xultophy, Victoza, Wegovy and Victoza from Novo Nordisk as well as Trulicity and Byetta from Eli Lilly, Bydureon from AstraZeneca and Lyxumia and Suliqua from Sanofi. Saxenda already contains a warning about “suicidal behaviour and suicidal ideation”.

Following a lawsuit over gastrointestinal side effects of Novo Nordisk’s and Eli Lilly’s slimming drugs – intestinal obstruction is already warned of as a rare side effect – and hundreds of reports from the FDA Adverse Event Reporting System (FAERS), the US agency is now also investigating whether GLP1 agonists promote hair loss, suicidal thoughts and aspiration, in which people undergoing surgery inhale food, liquids, vomit or saliva into the lungs. However, a recent study published in Nature (10.1038/s41591-023-02672-2) found no causal link between the administration of semaglutide and suicidal thoughts.

The side effects have been discussed for years in connection with the versions of GLP-1 agonists authorised for diabetes. In the course of the immense demand for an extension of the indication to obesity patients, they are receiving greater public attention. The developers Novo Nordisk and Eli Lilly said that they were working closely with the FDA – not least because the US market is considered the more lucrative and Novo had recently announced that it wanted to focus its business more on the USA due to bureaucratic hurdles in Europe. The Danish global market leader explained that side effects of semaglutide had not only been intensively monitored since yesterday and that data on 9.5 million patient years was available.