Label Update: FDA Requests Removal of Suicidal Ideation and Behavior Warning for GLP-1 Weight Management Drugs

FDA has requested that drug manufacturers remove suicidal ideation and behavior (SI/B) warnings from the labeling of three GLP-1 receptor agonist (GLP-1 RA) medications used for weight management: Saxenda (liraglutide), Wegovy (semaglutide), and Zepbound (tirzepatide). This action follows a comprehensive FDA review that found no evidence of increased SI/B risk associated with these drugs, bringing their labeling into alignment with other GLP-1 RAs approved for type 2 diabetes, which do not carry such warnings.

The SI/B warnings were originally included at approval for these weight-loss indications, based on historical reports from older obesity medications rather than GLP-1 RA-specific data. In July 2023, FDA began investigating postmarketing SI/B reports with GLP-1 RAs, issuing a preliminary January 2024 update noting no clear clinical trial signal but uncertainty due to limited cases.

FDA conducted a meta-analysis of 91 placebo-controlled GLP-1 RA trials (107,910 patients: 60,338 on GLP-1 RA, 47,572 on placebo), finding no increased SI/B risk or related psychiatric events like anxiety, depression, irritability, or psychosis. A retrospective cohort study using FDA Sentinel System data compared 1.16 million new GLP-1 RA users to 1.08 million SGLT2i users in type 2 diabetes patients (2015–2023), showing no elevated intentional self-harm risk, including the obesity subgroup. Published observational studies further confirmed no causal link.

Patients should continue GLP-1 RA medications as prescribed, reporting new/worsening depression, suicidal thoughts, or mood changes to providers. Those experiencing SI/B should seek immediate mental health evaluation via resources like the 988 Suicide & Crisis Lifeline. Healthcare professionals can reassure patients of these safety findings, discuss upcoming label updates, and report adverse events via MedWatch.

GLP-1 RAs mimic the gut hormone GLP-1 to lower post-meal blood sugar and suppress appetite via brain signaling. First approved in 2005 for type 2 diabetes glycemic control, the class has expanded significantly for obesity management.

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