FDA seeks changes to GLP-1, flu shot labels
The FDA has asked manufacturers of GLP-1 agonist medicines used for weight loss to remove warnings that they may cause suicidal thoughts.
The request – applying to Novo Nordisk's Wegovy (semaglutide) and Saxenda (liraglutide), as well as Eli Lilly's Zepbound (tirzepatide) – follows a new review of the drugs' safety, which the agency said did not identify any increased risk. The warnings are not included on formulations of the drugs used to treat diabetes, and do not appear on the drugs in Europe.
Concerns about suicidal ideation with GLP-1 drugs first emerged in 2023, when a few cases of suicidal thinking and self-harm were reported in patients using the medicines. That prompted a review by the FDA and EMA, which both concluded there was no risk in 2024.
Later that year, however, a new observational study published in JAMA Network Open reignited the debate around the safety of the class, prompting the FDA to take another look.
It carried out its own meta-analysis of 91 clinical trials across GLP-1 drug development programmes – involving more than 100,000 subjects – to improve its estimate of the risk, and also conducted a review of healthcare claims data to compare the risk of intentional self-harm with SGLT2 inhibitors used to treat diabetes.
"The results did not show an increased risk for [suicidal ideation/behaviour] or for other relevant psychiatric adverse events such as anxiety, depression, irritability, or psychosis," according to the regulator.
The move removes a potential brake on the use of GLP-1s just as a new class of oral medicines is starting to reach the market, spearheaded by Novo Nordisk's already-launched Wegovy pill, with Lilly's orforglipron poised potentially to join it in the next few weeks.
Flu shot warnings
Meanwhile, the FDA has asked manufacturers of flu vaccines to update their labels to include warnings about the risk of febrile seizures, saying that two post-marketing observational studies showed an increased risk during the first day after dosing of trivalent and quadrivalent shots in children aged six months to four years.
Letters asking for the changes have been sent to GSK, which makes Flulaval and Fluarix, AstraZeneca (FluMist), Sanofi (Fluzone), and Seqirus (Afluria and Flucelvax) from Center for Biologics Evaluation and Research (CBER) director Vinay Prasad.
Febrile seizures are relatively common in children in this age range, affecting between 2% and 5% of them, and are generally not linked to any long-term problems. They can be precipitated by infections, including colds and flu. The CDC currently recommends annual vaccination for people aged six months and older to prevent serious illness, hospitalisations, and death.
The changes to the labels come as the CDC is in the midst of major changes to the recommended US childhood immunisation schedule, which include a change in the status of flu vaccines from recommended to 'shared clinical decision-making'. The changes are being challenged by medical organisations, including the American Academy of Paediatrics (AAP), in a lawsuit.
The suit is seeking to enjoin the February meeting of the CDC's Advisory Committee on Immunisation Practices (ACIP) and block the changes. Earlier this month, a US district court denied a move by the HHS to dismiss the case.
