Typically, when the FDA issues a labeling safety warning, it means that a new warning is being added to existing labeling. However, in an FDA safety notice published today titled FDA Requests Removal of Suicidal Behavior and Ideation [SI/B] Warning from Glucagon-Like Peptide-1 Receptor Agonist (GLP-1 RA) Medications (here), the FDA is advising GLP-1 RA manufacturers for Saxenda (liraglutide), Wegovy (semaglutide), and Zepbound (tirzepatide) that already have the warning in approved labeling that the warning can be removed.
The notice says, “Health care professionals should be aware that FDA found no increased risk of SI/B with the use of GLP-1 RA medications and is requesting the removal of this Warning and Precaution from the prescribing information for the GLP-1 RA medications (Saxenda, Wegovy, and Zepbound) that include such language. Health care professionals should be prepared to discuss with patients that FDA has found no increased risk after conducting a comprehensive review of the available data.” The notice also suggests that healthcare providers continue to report any SI/B events to the FDA and advises patients to seek appropriate mental health services.
The notice goes on to say that “In July 2023, after receiving postmarketing reports of SI/B in patients taking GLP-1 RA medications, FDA initiated further investigation of the potential risk of SI/B for GLP-1 RA medications. FDA performed a preliminary review of clinical trial and postmarketing data, including observational studies and case reports, and publicly reported those findings in its January 2024 Drug Safety Communication.”
“The initial review of GLP-1 RA clinical trial data did not find an association between the use of GLP-1 RAs and the occurrence of SI/B. However, because of the small number of cases of SI/B observed in individual trials, there was considerable uncertainty in the risk estimate. To address this concern, FDA performed a comprehensive meta-analysis of clinical trials across GLP-1 RA drug development programs to improve the precision of the risk estimate. The meta-analysis assessed the risk of SI/B comparing GLP-1 RA medications to placebo. There were 91 placebo-controlled GLP-1 RA medication trials in the meta-analysis that included 107,910 patients (60,338 treated with a GLP-1 RA and 47,572 treated with placebo). The results did not show an increased risk for SI/B or for other relevant psychiatric adverse events such as anxiety, depression, irritability, or psychosis.”
The initial warning was included in the labeling for the GLP-1 RA for weight loss because it was included in the labeling of other products indicated for weight loss. After reexamination of the issue, the FDA determined the warning was not appropriate for GLP-1 RA products. This is good news for the companies that manufacture these products as well as for patients.
