The FDA requested that manufacturers of GLP-1 receptor agonists (RAs) remove the warning regarding the risk of suicidal ideation and behavior (SI/B) from the drugs’ labeling. 

Affected products are Novo Nordisk’s Saxenda (liraglutide) and Wegovy (semaglutide) and Eli Lilly’s Zepbound (tirzepatide). Both companies welcomed the news but did not provide a timeline for the label change at press time.

What the FDA Did

In July 2023, after receiving reports of SI/B in patients taking GLP-1 RAs, the FDA performed a preliminary review of clinical trial and postmarketing data, including case reports and observational studies. As reported in 2024, no association was found. But because of the small number of cases reporting SI/B, the risk estimate was uncertain.

To address the uncertainty, the FDA performed a meta-analysis of clinical trials across GLP-1 RA drug-development programs to improve the precision of the risk estimate. The meta-analysis included 91 placebo-controlled GLP-1 RA drug trials with a total of 107,910 patients (60,338 treated with a GLP-1 RA and 47,572 treated with placebo). The results did not show an increased risk for SI/B or for other relevant psychiatric adverse events such as anxiety, depression, irritability, or psychosis. 

The FDA also conducted a retrospective cohort study of more than 2 million users and assessed published observational and pooled studies evaluating the relationship between GLP-1 RAs and SI/B and related outcomes. The review concluded that “the totality of these studies does not support a causal relationship between the use of GLP-1 RAs and the occurrence of SI/B.”

The new removal request states, “Health care professionals should be prepared to discuss with patients that FDA has found no increased risk after conducting a comprehensive review of the available data. If individuals disclose that they are experiencing SI/B, refer them to mental health professionals for evaluation.” 

What Other Countries Say

The European Medicines Agency came to the same conclusion as the FDA after conducting its own analyses. Health Canada’s safety review did not find evidence to support a link between GLP-1 RAs and the risks of suicide, self-harm, and suicidal/self-harm ideation in patients with type 2 diabetes but noted that there was not enough information to determine if there is a link in patients with obesity.

Australia aimed to harmonize labeling across the class. Therefore, the Therapeutic Goods Administration said, “The following wording has been added to the PIs for all GLP-1 RAs (except Saxenda as it already included suitable wording): Suicidal behavior and ideation have been reported with GLP-1 RAs. Monitor patients for the emergence or worsening of depression, suicidal thoughts or behaviors, and/or any unusual changes in mood or behavior. Consider the benefits and risks for individual patients prior to initiating or continuing therapy in patients with suicidal thoughts or behaviors or have a history of suicidal attempts.”

Marilynn Larkin, MA, is an award-winning medical writer and editor whose work has appeared in numerous publications, including Medscape Medical News and its sister publication MDedge, The Lancet (where she was a contributing editor), and Reuters Health.