FDA asks Lilly to update the Zepbound label over intestinal obstruction reports

The Food and Drug Administration has approved changes to the prescribing information for Zepbound (tirzepatide), Eli Lilly's obesity drug, requiring new warnings about intestinal obstruction and severe constipation, including fecal impaction ^[1]. The change follows an FDA review of a safety signal that applies not just to Zepbound but to the entire class of GLP-1 receptor agonist medicines, which also includes semaglutide products like Ozempic, Wegovy, and Rybelsus ^[1].

The process began on April 28, 2025, when the FDA sent Lilly a Notification of Newly Identified Safety Signal, telling the company it was evaluating reports of intestinal obstruction and fecal impaction linked to GLP-1 drugs as a class ^[1]. After completing that review, the agency sent Lilly a formal supplement request letter on October 14, 2025, directing the company to update the Zepbound label ^[1]. Lilly submitted its response, a supplemental new drug application, on November 14, 2025 ^[1].

The approved label now includes a new statement in the Warnings and Precautions section, under the heading "Severe Gastrointestinal Adverse Reactions," saying that "severe gastrointestinal adverse reactions have also been reported postmarketing with GLP-1 receptor agonists" ^[1]. The Adverse Reactions section, under "Postmarketing Experience," now lists "intestinal obstruction, severe constipation including fecal impaction" ^[1]. Postmarketing reports are cases that surface after a drug is on the market and are not the same as findings from controlled clinical trials, though the FDA can still require label changes based on them.

In the same approval, the FDA also removed a different warning from the Zepbound label. In 2023, the agency had flagged a separate safety signal involving suicidal ideation across the GLP-1 class and asked Lilly to add a warning, which appeared as Section 5.9 of the label ^[1]. After further review, the FDA sent Lilly a new supplement request letter on January 13, 2026, asking the company to remove that suicidal ideation section from the Warnings and Precautions, along with related mentions in other parts of the label and in the Medication Guide's list of possible side effects ^[1]. Both the gastrointestinal addition and the suicidal ideation removal were folded into the same supplement, rather than handled as two separate filings ^[1].

Why it matters for patients

For people taking Zepbound, or considering it, the updated label means intestinal obstruction and severe constipation with fecal impaction are now explicitly listed as reactions reported after the drug reached the market ^[1]. This does not tell patients how common these problems are or confirm that Zepbound caused them in any specific case; postmarketing reports reflect what has been reported to the FDA, not a measured rate from a controlled study. Because the underlying safety signal was evaluated across the whole GLP-1 class, not just tirzepatide, similar labeling conversations could affect other GLP-1 medicines as well, though this document only confirms action on Zepbound ^[1].

At the same time, the removal of the suicidal ideation warning shows that FDA's evaluation of a different signal moved in the opposite direction, concluding after further review that the information should come off the label rather than stay ^[1]. Patients and prescribers relying on drug labeling to understand risks may want to know that both these changes reflect the FDA's ongoing tracking of side effects after a drug is approved, and that such reviews can add or remove warnings as new evidence comes in.

What happens next

Lilly must submit the finalized label content to the FDA's structured labeling system within 14 days of the approval letter, and the updated Prescribing Information and Medication Guide will then become part of the publicly available label ^[1]. The company is also required to revise any promotional materials to reflect the new safety information ^[1].