Leo Sher, M.D.

The Food and Drug Administration (FDA) has requested that manufacturers remove the warning for suicidal ideation and behavior from prescribing information for glucagon-like peptide-1 receptor agonist (GLP-1 RA) medications (1). GLP-1 RA medications are a class of drugs that mimic the action of the endogenous GLP-1 hormone, enhancing glucose-dependent insulin secretion, suppressing glucagon release, and slowing gastric emptying (2). They are widely used for the treatment of type 2 diabetes and obesity due to their effects on glycemic control, appetite regulation, and weight reduction.

The FDA conducted a comprehensive meta-analysis of randomized clinical trials comparing GLP-1 RA therapies with placebo to evaluate the risk of suicidal ideation and behavior. The analysis included 91 trials encompassing 107,910 patients, of whom 60,338 received a GLP-1 RA and 47,572 received placebo. The findings demonstrated no increased risk of suicidal ideation and behavior associated with GLP-1 RA use compared with placebo. Similarly, no elevated risk was observed for other psychiatric adverse events, including anxiety, depression, irritability, or psychosis. In addition, the FDA reviewed observational and pooled studies assessing the relationship between GLP-1 RAs and suicidal ideation and behavior. Taken together, these data led the FDA to conclude that there is no causal relationship between GLP-1 RA medications and the occurrence of suicidal ideation or behavior.

Accordingly, the FDA is directing manufacturers to remove the suicidal ideation and behavior warning from the labeling of the weight-loss medications Saxenda (liraglutide), Wegovy (semaglutide), and Zepbound (tirzepatide). GLP-1 RA medications indicated for the treatment of type 2 diabetes do not include this warning in their labeling.

References

1. US Food and Drug Administration. FDA requests removal of suicidal behavior and ideation warning from glucagon-like peptide-1 receptor agonist (GLP-1 RA) medications. January 13, 2026. URL: https://www.fda.gov/media/190557/download?attachment.
2. Nauck MA, Tuttle KR, Tschöp MH, Blüher M. Glucagon-like receptor agonists and next-generation incretin-based medications: metabolic, cardiovascular, and renal benefits. Lancet. 2026 Jan 14:S0140-6736(25)02105-1. doi: 10.1016/S0140-6736(25)02105-1. Epub ahead of print.