FDA Requests Removal of Suicide Risk Warnings From GLP-1 RA Labels
Key Clinical Summary
- A US Food and Drug Administration (FDA) review found no increased risk of suicidal ideation or behavior with glucagon-like peptide-1 receptor agonist (GLP-1 RA) use.
- Labeling changes were requested for weight-management drugs including semaglutide, liraglutide, and tirzepatide.
- Evidence included meta-analysis of 91 trials and large real-world data from over 2.2 million patients.
The US Food and Drug Administration (FDA) has requested the removal of information regarding the risk of suicidal ideation and behaviors (SI/B) from the labeling of glucagon-like peptide-1 receptor agonist (GLP-1 RA) medications. The announcement follows a comprehensive FDA review that found no significant association between GLP-1 RA use and SI/B risk.
Regulatory Context and Review Findings
The FDA request applies to GLP-1 RA medications approved for chronic weight management, including liraglutide, semaglutide, and tirzepatide. These products previously included SI/B warnings in their Warnings and Precautions sections based on historical concerns observed with older weight loss drugs.
In July 2023, the FDA initiated a formal investigation after receiving postmarketing reports of suicidal ideation and behavior in patients using GLP-1 RAs. Preliminary findings were shared in a January 2024 Drug Safety Communication, noting no clear association but acknowledging uncertainty due to limited event numbers.
To improve risk estimation, the FDA conducted a large meta-analysis of 91 placebo-controlled clinical trials across GLP-1 RA development programs. The analysis included 107,910 participants, with 60,338 treated with a GLP-1 RA and 47,572 receiving placebo. Results showed no increased risk of suicidal ideation, behavior, or related psychiatric adverse events, including anxiety, depression, irritability, or psychosis.
The agency also performed a retrospective cohort study using FDA Sentinel System claims data. This analysis compared new users of GLP-1 RAs with users of sodium-glucose cotransporter 2 inhibitors (SGLT2i) among 2,243,138 patients with type 2 diabetes between October 2015 and September 2023. After adjustment for baseline confounders, no increased risk of intentional self-harm was observed with GLP-1 RAs, including among patients with concurrent obesity.
Clinical Implications
The agency emphasized that clinicians should continue routine monitoring of mental health symptoms as part of comprehensive obesity and diabetes care, but the findings suggest no need for heightened concern specific to GLP-1 RA therapy.
The labeling change may also help address patient anxiety driven by prior warnings, which could have contributed to medication hesitancy or misattribution of baseline psychiatric symptoms to GLP-1 RA therapy. Psychiatric providers can use these data to contextualize suicide risk discussions and reinforce that current evidence does not support a causal link between GLP-1 RAs and suicidal behavior.
