Lilly files the supplement that would remove Zepbound's suicidal ideation warning

The Food and Drug Administration has approved a labeling supplement for Zepbound (tirzepatide) that adds language about intestinal blockage and severe constipation while removing the drug's warning about suicidal thoughts and behavior, according to an approval letter for supplement S-042 ^[1]. Eli Lilly submitted the supplement on November 14, 2025, but the FDA folded a second, unrelated labeling request into the same review before signing off on February 25, 2026 ^[1].

The gastrointestinal changes trace back to an FDA safety review that began in April 2025. On April 28, 2025, the agency told Lilly it was evaluating a "newly identified safety signal" for intestinal obstruction and fecal impaction across the whole class of GLP-1 receptor agonist drugs, which includes Zepbound ^[1]. On October 14, 2025, the FDA formally requested a label update, and the approved changes now add a statement to the Warnings and Precautions section saying "severe gastrointestinal adverse reactions have also been reported postmarketing with GLP-1 receptor agonists," plus new entries for "intestinal obstruction, severe constipation including fecal impaction" under Postmarketing Experience ^[1].

The suicidal ideation change has a longer and separate history. The FDA first told Lilly on July 21, 2023, that it was reviewing a safety signal for suicidal ideation tied to the GLP-1 drug class ^[1]. That review apparently led to a warning being added to Zepbound's label at some point. But on January 13, 2026, the FDA sent Lilly a new request letter asking for that warning to be taken out ^[1]. Rather than open a separate supplement, the FDA says it made the change "during review of S-042" ^[1]. The approved label now removes subsection 5.9, "Suicidal Ideation and Behavior," from the Warnings and Precautions section, along with matching updates to the Highlights, Table of Contents, and other sections of the prescribing information ^[1]. The patient Medication Guide also drops the phrase "depression or thoughts of suicide" from its list of possible side effects ^[1].

Why it matters for patients

People using Zepbound will see two changes moving in opposite directions on the same label. The new gastrointestinal wording flags a risk — intestinal blockage and severe constipation — that had not previously appeared in the postmarketing section ^[1]. At the same time, the specific warning about suicidal thoughts is being removed from both the prescribing information and the patient Medication Guide ^[1]. The FDA's letter does not explain its reasoning for the reversal beyond noting that it issued the removal request itself in January 2026 ^[1]; the underlying evidence review is not part of this document.

It is not clear from this letter whether similar changes are happening, or will happen, to labels for other GLP-1 drugs such as Wegovy, Ozempic, Rybelsus, Mounjaro, or Foundayo, since both safety signals were described as affecting the drug class broadly but this action applies specifically to Zepbound ^[1].

What happens next

The approval is effective as of the date of the letter ^[1]. Lilly must submit the updated label in a standard electronic format within 14 days, and must also send a written statement of intent to update its promotional materials within 7 days of receiving the letter ^[1]. Any patent information tied to the change is due to the FDA within 30 days of approval ^[1]. The letter is signed by Monika Houstoun, Deputy Director for Safety in the FDA's Division of Diabetes, Lipid Disorders, and Obesity, dated February 25, 2026 ^[1].