FDA approves Zepbound label change dropping suicidality warning, adding intestinal obstruction

On February 25, 2026, the FDA approved a labeling supplement for Zepbound (tirzepatide) that removes the warning about suicidal ideation and behavior and adds intestinal obstruction and severe constipation, including fecal impaction, to the list of reactions reported after the drug reached the market ^[1][3].

The approval covers supplement S-042 to new drug application 217806, which Eli Lilly submitted on November 14, 2025 ^[1]. The FDA's approval letter says the agency told Lilly on April 28, 2025 that it was evaluating a newly identified safety signal for intestinal obstruction and fecal impaction across the GLP-1 receptor agonist class, which includes Zepbound. On October 14, 2025, the FDA sent a supplement request letter asking the company to update the labeling based on that evaluation ^[1].

Two gastrointestinal changes resulted. In Section 5, Warnings and Precautions, under Severe Gastrointestinal Adverse Reactions, the label now states: "Severe gastrointestinal adverse reactions have also been reported postmarketing with GLP-1 receptor agonists" ^[1][3]. In Section 6, Adverse Reactions, under Postmarketing Experience, the label now lists "intestinal obstruction, severe constipation including fecal impaction" ^[1][3].

The label also gives rates for severe gastrointestinal reactions seen in trials. In a pool of two Zepbound trials for weight reduction, severe gastrointestinal adverse reactions were reported in 1.7 percent of patients taking 5 mg, 2.5 percent taking 10 mg and 3.1 percent taking 15 mg, compared with 1 percent of those taking placebo. The label says similar rates appeared in the weight-reduction trials and in the trials for obstructive sleep apnea ^[3]. Zepbound is approved to reduce excess weight and maintain weight reduction in adults with obesity or with overweight plus at least one weight-related condition, and to treat moderate to severe obstructive sleep apnea in adults with obesity ^[2].

The suicidality change came from a separate review. The FDA notified Lilly on July 21, 2023 that it was evaluating a newly identified safety signal for suicidal ideation for the GLP-1 receptor agonist class ^[1]. On January 13, 2026, the agency sent a supplement request letter asking for removal of suicidal ideation information from the Zepbound label. The approval letter says those changes were made during review of S-042 rather than in a separate supplement ^[1].

As a result, subsection 5.9, Suicidal Ideation and Behavior, is gone from the Warnings and Precautions section, with matching updates to the Highlights, Table of Contents, Section 6, Section 17 and the Recent Major Changes section. The Medication Guide no longer lists "depression or thoughts of suicide" among possible side effects ^[1]. DailyMed labeling updated August 28, 2026 lists "Suicidal Behavior and Ideation (Removed)" as a recent major change dated 02/2026, and the 5.9 slot now covers pulmonary aspiration during general anesthesia or deep sedation ^[2].

Why it matters for patients

Both changes are written into the prescribing information and Medication Guide that patients and clinicians read. Anyone looking for the old suicidality warning in newly updated labeling will not find it ^[1][2].

The approval letter does not explain the basis for removing the suicidality information, and no conclusion about whether GLP-1 drugs cause suicidal thoughts has been disclosed. The letter describes only the sequence of reviews and the requested edits ^[1].

Intestinal obstruction and severe constipation including fecal impaction are listed as postmarketing reports, meaning they were reported after approval rather than measured in the clinical trials. The label gives no frequency or rate for these events, and no rate has been reported ^[1][3].

The Warnings and Precautions section still says Zepbound is not recommended in patients with severe gastroparesis ^[2]. The Medication Guide continues to describe dehydration leading to kidney problems and pancreatitis, among other reactions ^[3].

What happens next

Lilly was required to submit the updated labeling in structured product labeling format within 14 days of the February 25, 2026 approval. Within 7 days, the company was required to submit a statement of intent to comply with rules that promotional materials be revised to match the new labeling, including the new safety information ^[1].

The DailyMed listing for Zepbound shows the label was updated August 28, 2026 ^[2]. The FDA's approval letter covers Zepbound only and does not say whether labels for other GLP-1 receptor agonists will change ^[1].