GLP-1 Warning Removal Shows How FDA Changes Drug Safety Labeling

The Food and Drug Administration said on January 13 that it is asking the holders of three weight-loss drug approvals to remove a warning about suicidal ideation and behavior from their labeling. The Drug Safety Communication names Saxenda (liraglutide), Wegovy (semaglutide) and Zepbound (tirzepatide), all GLP-1 receptor agonists approved for weight reduction. Their labels have carried the information in the Warnings and Precautions section since approval. Labels for GLP-1 drugs approved for type 2 diabetes never included it, and FDA said the change will make messaging consistent across the class.

Drug labels are not fixed at approval. The GLP-1 request is one example of how safety information moves onto, and off, a label as evidence builds.

How FDA reached the decision

FDA said it began investigating in July 2023 after receiving postmarketing reports of suicidal ideation and behavior in patients taking GLP-1 drugs, and published preliminary findings in a January 2024 Drug Safety Communication. Because individual trials had few such cases, the agency then ran a meta-analysis of 91 placebo-controlled trials covering 107,910 patients. It found no increased risk of suicidal ideation or behavior, or of related psychiatric events such as anxiety, depression or psychosis, according to the communication.

FDA also used its Sentinel System, which draws on administrative health care claims data, to compare intentional self-harm among 2,243,138 new users of GLP-1 drugs or SGLT2 inhibitors with type 2 diabetes from 2015 to 2023, and found no increased risk. It said the totality of published observational and pooled studies "does not support a causal relationship" between the drugs and such events, and requested the removal on that basis.

The power to require new warnings

Adding a warning works differently. Section 505(o)(4) of the Federal Food, Drug, and Cosmetic Act authorizes FDA to require holders of approved new drug applications, biologics licenses and some generic applications to change labeling based on "new safety information" that emerges after approval, according to FDA's September 2025 draft guidance on safety labeling changes, which would replace a 2013 version. New safety information can come from clinical trials, adverse event reports, postapproval studies, published literature or FDA's postmarket risk analysis system, and must concern a serious or unexpected serious risk.

The process runs on short deadlines. FDA sends a notification letter describing the new information and proposed wording. Within 30 days the holder must either submit a labeling supplement or a rebuttal saying why no change is warranted. If FDA finds the response inadequate, or gets none, it can issue a safety labeling change order after a discussion period; the holder then has 15 days to submit the change or 5 days to appeal. Failing to do either violates the statute, the guidance says. FDA anticipates such orders "will be rare." It posts all order letters but not routine notification letters.

Changes outside that process

Not every label change goes through section 505(o)(4). New information about a nonserious risk does not meet its criteria, and holders can submit labeling supplements on their own at any time under FDA's standard supplement rules, the draft guidance says. A prior approval supplement needs FDA approval before the change is distributed; a "changes being effected" supplement can be put into use once FDA receives it.

The GLP-1 action is a request to the application holders, not a safety labeling change order, and it takes information off the label rather than adding a new risk.