The FDA has announced a significant update affecting several widely prescribed glucagon-like peptide-1 receptor agonists (GLP-1 RAs), requesting the removal of labeling language related to suicidal ideation and behavior (SI/B) for select agents used in obesity treatment. This decision follows an extensive, multi-method safety evaluation that found no evidence of increased risk for suicidality or other major psychiatric adverse events associated with GLP-1 RA use.
What Changed?
The FDA is asking manufacturers to remove SI/B warnings from the prescribing information for:
- Saxenda (liraglutide)
- Wegovy (semaglutide)
- Zepbound (tirzepatide)
These warnings had been included at the time of approval based on historical concerns seen with older weight-loss medications, not because of clear signals emerging from GLP-1 RA clinical trials. Notably, GLP-1 RAs approved for type 2 diabetes had never carried SI/B warnings, creating inconsistency across the class. The FDA’s action aligns labeling across all GLP-1 receptor agonists.
Why This Matters to Mental Health Clinicians
GLP-1 RAs are increasingly prescribed to patients with obesity, diabetes, and metabolic syndrome—conditions that frequently co-occur with depression, anxiety, and other psychiatric disorders. Concerns about suicidality have led some clinicians to hesitate when prescribing or co-managing these medications in patients with psychiatric histories.
The FDA’s conclusion is based on one of the most robust psychiatric safety evaluations conducted for this drug class to date.
The FDA’s determination was based on a comprehensive review of multiple complementary data sources. This included a meta-analysis of 91 randomized, placebo-controlled trials involving 107,910 participants, which found no increased risk of suicidal ideation, suicidal behavior, depression, anxiety, irritability, or psychosis compared with placebo. The FDA also analyzed data from a large retrospective cohort study using the FDA Sentinel System, encompassing more than 2.2 million patients initiating either a GLP-1 receptor agonist or an SGLT2 inhibitor, and observed no increased risk of intentional self-harm among GLP-1 receptor agonist users, including individuals with obesity and type 2 diabetes. Additionally, a review of published observational and pooled studies found that the totality of evidence did not support a causal relationship between GLP-1 receptor agonists and suicidality.
What Should Clinicians Do Now?
Clinicians should continue routine assessment of mood and suicidality as clinically indicated, particularly in patients with preexisting psychiatric illness, while reassuring patients who may have encountered concerning media coverage that the FDA’s review found no increased risk associated with GLP-1 receptor agonists.
Ongoing pharmacovigilance remains important, and clinicians are encouraged to continue reporting adverse events through FDA MedWatch despite the reassuring data. In summary, following an extensive and methodologically rigorous review, the FDA concluded that current evidence does not demonstrate an increased risk of suicidal ideation or behavior with GLP-1 receptor agonists. The removal of suicidality-related warnings reflects growing confidence in the psychiatric safety profile of this increasingly important medication class, with meaningful implications for clinicians caring for patients at the intersection of metabolic and mental health treatment.