The agency nevertheless said that it could not definitively rule out a small risk of suicidal ideation associated with GLP-1 receptor agonists, and that it will continue evaluating the evidence.
Pictured: FDA signage outside its office in Washington, DC/iStock, JHVEPhoto
The FDA on Thursday announced that its preliminary review has returned no evidence linking GLP-1 receptor agonists with an increased risk of suicidal thoughts.
The regulator has also advised patients not to discontinue their GLP-1 medications without consulting—or unless recommended by—their physician, as this might aggravate their condition. Meanwhile, doctors and other healthcare professionals are advised to closely monitor their patients for worsening depression, suicidal thoughts, any changes in mood and behavior and other concerning side effects.
The FDA last week launched an investigation into GLP-1 receptor agonists after its Adverse Event Reporting System picked up several patient reports of suicidal ideation between July 2023 and September 2023. The probe included the widely popular weight-loss drugs Wegovy (semaglutide), from Novo Nordisk, and Zepbound (tirzepatide), manufactured by Eli Lilly.
According to the regulator, being included in its Adverse Event Reporting System list does not necessarily mean that the FDA “has concluded that the drug has the listed risk.” The drug class is also under investigation for alopecia and aspiration, which is the accidental inhalation of foreign objects.
In its advisory on Thursday, the regulator noted that because the information it received was “often limited” and because other potential factors could have affected the suicidal thoughts, “we determined that the information in these reports did not demonstrate a clear relationship with the use” of GLP-1 receptor agonists.
“However, because of the small number of suicidal thoughts or actions observed in both people using GLP-1 RAs and in the comparative control groups, we cannot definitively rule out that a small risk may exist,” the FDA cautioned, adding that it will continue to evaluate the data and assess the potential risk of suicidal ideation associated with the drug class.
The FDA’s findings echo the conclusions of a recent study published in Nature Medicine showing that in a population of more than 240,000 overweight or obese participants, treatment with semaglutide did not significantly aggravate the risk of suicidal ideation. In fact, Novo’s molecule showed a significant protective effect against the outcome—though the authors were quick to point out the weaknesses and limitations of their study and the need for future investigations to confirm their findings.
GLP-1 receptor agonists mimic the GLP-1 hormone and act on the pancreas, inducing the secretion of insulin into the bloodstream in response to changes in glucose concentrations. This mechanism of action allows GLP-1 receptor agonists to be effective at treating diabetes and for managing weight, which in turn has resulted in staggering demand—and market potential—for these drugs.
Aside from Wegovy and Zepbound, other therapies in this class include Novo’s Ozempic, Saxenda and Victoza, and Lilly’s Mounjaro and Trulicity.
In recent months, however, the drug class has been hounded by safety concerns, including the possible risk of self-harm and suicidal ideation, as well as gastrointestinal toxicities.
Tristan Manalac is an independent science writer based in Metro Manila, Philippines. He can be reached at tristan@tristanmanalac.com or tristan.manalac@biospace.com.
