Preliminary FDA review finds no link between suicidal thoughts and weight-loss drugs

Key takeaways:

• The FDA said evidence was limited because of a lack of information and the possibility of other factors.
• The agency will continue to investigate the issue after it could not definitively rule out a small risk.

Preliminary results from an ongoing FDA investigation found no evidence that weight-loss drugs cause suicidal ideations and aspirations, although the agency said it cannot rule out a risk entirely.

In a quarterly report released on Jan. 2, the FDA revealed it was investigating potential safety signals of popular weight-loss medications like Ozempic (semaglutide, Novo Nordisk), Wegovy (semaglutide, Novo Nordisk) Mounjaro (tirzepatide, Eli Lilly), Zepbound (tirzepatide, Eli Lilly) and Saxenda (liraglutide, Novo Nordisk). Semaglutide and liraglutide are both GLP-1 receptor agonists, whereas tirzepatide is a GIP/GLP-1 dual agonist.

These safety risks included alopecia, a hair loss condition, and suicidal thoughts and aspirations.

A recent retrospective cohort study published in Nature Medicine found that GLP-1 agonists were linked to a lower risk for incident suicidal ideation (HR = 0.27) and recurrent suicidal ideation (HR = 0.44) compared with other drugs for obesity and type 2 diabetes.

According to an FDA safety communication, the information provided to the agency’s adverse event reporting system was often limited. Because of this and the fact that suicidal thoughts or actions could be influenced by other factors, the FDA said that it did not find a clear causal link.

“Similarly, our reviews of the clinical trials, including large outcome studies and observational studies, did not find an association between use of GLP-1 RAs and the occurrence of suicidal thoughts or actions,” the report said.

However, the FDA noted that because of the small number of suicidal ideations and aspirations observed from people in both the control groups and those using GLP-1 agonists, it cannot disregard the possibility of a small risk and will continue to investigate the issue.

“We will communicate our final conclusions and recommendations after we complete our review or have more information to share,” the report said.

The agency encouraged health care professionals to continue monitoring and advising patients on GLP-1 agonists to report any new or worsening symptoms of depression or suicidal thoughts.

In a previous statement to Healio, Novo Nordisk, the manufacturer of Ozempic, Wegovy and Saxenda, said that the safety of patients “is the top priority” for the company.

“Novo Nordisk stands behind the safety and efficacy of all of our GLP-1RA medicines when they are used as indicated and when they are taken under the care of a licensed health care professional,” the statement said.

References:

• FDA. https://www.fda.gov/drugs/questions-and-answers-fdas-adverse-event-reporting-system-faers/july-september-2023-potential-signals-serious-risksnew-safety-information-identified-fda-adverse. Published Jan. 2, 2024. Accessed Jan. 12, 2024.
• Potential Signals of Serious Risks/New Safety Information Identified from the FDA Adverse Event Reporting System (FAERS). https://www.fda.gov/drugs/questions-and-answers-fdas-adverse-event-reporting-system-faers/potential-signals-serious-risksnew-safety-information-identified-fda-adverse-event-reporting-system. Accessed Jan. 12, 2023.
• 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. https://www.fda.gov/drugs/drug-safety-and-availability/update-fdas-ongoing-evaluation-reports-suicidal-thoughts-or-actions-patients-taking-certain-type. Published Jan. 11, 2023. Accessed Jan. 12, 2023.
• Wang W, et al. Nat Med. 2023;doi:10.1038/s41591-023-02672-2.