FDA Review Suggest No Link Between GLP-1RAs and Suicidal Thoughts but Surveillance Will Continue

A preliminary review by the US Food and Drug Administration (FDA) of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) used to treat patients with type 2 diabetes or obesity finds there is no evidence they cause suicidal thoughts or actions, regulators said in a safety communication on Thursday. But because the risk cannot be ruled out, the agency will continue to evaluate the drugs.

Regulators have over the last few months reviewed the reports of suicidal thoughts or actions received in the FDA Adverse Event Reporting System (FAERS) related to these drugs (see below for list of drugs that have been evaluated). Information in the reports was often limited, according to the FDA, and the events themselves can be influenced by any number of other potential factors, leading the agency to conclude a clear link could not be drawn with the use of GLP-1RAs.

Similarly, the FDA’s review of large outcome studies and observational studies as well as other clinical trials found no association between use of GLP-1RAs and the occurrence of suicidal thoughts or actions. However, the number of suicidal thoughts or actions observed in both the control groups and groups treated with the medications was small, making it impossible to definitely rule out a small risk.

Thus surveillance will continue, the agency stated. Regulators will conduct additional evaluations, including of a large meta-analysis of clinical trials across all GLP-1RA products and a comprehensive analysis of postmarketing data in the Sentinel System, a large data network that contains health insurance claims and patient health records used to investigate questions about the safety of FDA-approved products.

The FDA advises that patients should not stop taking prescribed GLP-1RA medications without speaking with their health care professional.

FDA-Approved GLP-1RA Drugs

• Adlyxin (lixisenatide) type 2 diabetes (T2D)
• Bydureon BCise (exenatide) T2D
• Byetta (exenatide) T2D
• Mounjaro (tirzepatide) T2D
• Ozempic (semaglutide) T2D
• Rybelsus (semaglutide) T2D
• Saxenda (liraglutide) obesity/overweight
• Soliqua (lixisenatide + insulin glargine) T2D
• Trulicity (dulaglutide) T2D
• Victoza (liraglutide) T2D
• Wegovy (semaglutide) obesity/overweight
• Xultophy (liraglutide + insulin degludec) T2D
• Zepbound (tirzepatide) obesity/overweight

The agency urges health care professionals to monitor patients using GLP-1RAs for new or worsening depression, unusual changes in mood/behavior or suicidal thoughts and to counsel patients to report these symptoms. Current prescribing information for these drugs does contain information about risk for suicidal thoughts and actions, according to the agency. Similar information is included, too, in labeling for older classes of medicines either used or tested for weight loss, also based on reports of this type of mood disturbance.

Source: Update on FDA’s ongoing evaluation of reports of suicidal thoughts or actions in patients taking a certain type of medicines approved for type 2 diabetes and obesity. Drug Safety Communication. US Food and Drug Administration. January 11, 2024. Accessed January 12, 2024. https://www.fda.gov/drugs/drug-safety-and-availability/update-fdas-ongoing-evaluation-reports-suicidal-thoughts-or-actions-patients-taking-certain-type