Zepbound label drops the suicidality warning and adds intestinal obstruction

The FDA approved a labeling supplement for Eli Lilly's Zepbound (tirzepatide) on Feb. 25, 2026 that removes the drug's warning about suicidal ideation and behavior and, at the same time, adds intestinal obstruction and severe constipation including fecal impaction to the list of problems reported after the drug went on the market ^[1].

The approval, for supplement S-042 under NDA 217806, was signed by Monika Houstoun, Pharm.D., M.P.H., deputy director for safety in FDA's Division of Diabetes, Lipid Disorders, and Obesity ^[1]. It covers both Zepbound injection and the Zepbound KwikPen ^[1].

Two safety reviews, one supplement

The two changes came out of separate FDA safety reviews that ended up bundled together.

On the gut side, FDA emailed Lilly a Notification of Newly Identified Safety Signal on April 28, 2025, saying it was evaluating intestinal obstruction and fecal impaction across the whole GLP-1 receptor agonist class, which includes Zepbound ^[1]. FDA followed with a supplement request letter on Oct. 14, 2025, and Lilly filed the supplement on Nov. 14, 2025 ^[1].

That produced two specific edits. Section 5.2, Severe Gastrointestinal Adverse Reactions, now adds the sentence: "Severe gastrointestinal adverse reactions have also been reported postmarketing with GLP-1 receptor agonists" ^[1]. And the Postmarketing Experience list in Section 6.2 now reads: acute pancreatitis, hemorrhagic and necrotizing pancreatitis sometimes resulting in death, ileus, intestinal obstruction, severe constipation including fecal impaction ^[3]. Ileus was already on that list as of a September 2025 update; intestinal obstruction and fecal impaction are the new entries ^[3].

The rest of Section 5.2 is unchanged and still carries the trial numbers. In a pool of two Zepbound weight-reduction trials, severe gastrointestinal adverse reactions were reported more often with Zepbound — 1.7% at 5 mg, 2.5% at 10 mg and 3.1% at 15 mg — than with placebo at 1% ^[3]. Similar rates showed up in the obstructive sleep apnea trials ^[3]. The label still says Zepbound is not recommended in patients with severe gastroparesis ^[3].

The suicidality warning is gone

The second change traces back to a July 21, 2023 FDA signal notification about suicidal ideation for the GLP-1 class ^[1]. On Jan. 13, 2026, FDA issued a supplement request letter asking Lilly to remove that information from the Zepbound label, and the agency folded the change into its review of S-042 rather than requiring a separate filing ^[1].

The approval deletes subsection 5.9, Suicidal Ideation and Behavior, from Warnings and Precautions, with matching updates to the Highlights, Table of Contents, Section 6, Section 17 and Recent Major Changes ^[1]. The Medication Guide no longer lists "depression or thoughts of suicide" among possible side effects ^[1]. The FDA letter does not spell out the scientific reasoning behind the removal; that detail is not in the sources provided here.

The current Zepbound prescribing information on DailyMed reflects both moves. Its Recent Major Changes table lists Severe Gastrointestinal Adverse Reactions (5.2) as 02/2026 and "Suicidal Behavior and Ideation (Removed)" as 02/2026 ^[2]. The Warnings and Precautions summary now ends with pulmonary aspiration during anesthesia at 5.9 and the KwikPen sharing warning at 5.10 ^[2].

Why it matters for patients

Label text is what prescribers, pharmacists and insurers read, and it shapes what gets discussed at an appointment. Removing the suicidality subsection means Zepbound's official labeling no longer flags depression or suicidal thoughts as a listed serious side effect, and the Medication Guide handed out at the pharmacy will drop that line ^[1].

The gastrointestinal additions cut the other way. Intestinal obstruction and severe constipation including fecal impaction are now named in the label, which gives a clinician evaluating persistent constipation or abdominal symptoms a documented reference point. Postmarketing reports are voluntary and do not establish how often these events happen or that the drug caused them; the label does not attach a frequency to them ^[3].

What happens next

Lilly had 14 days from Feb. 25, 2026 to submit the new content of labeling in structured product labeling format, which is how the text reaches public databases ^[1]. Within 7 days of the letter, the company had to submit a statement of intent to bring promotional materials in line with the revised label, including prominent disclosure of new safety information ^[1]. The DailyMed label was last updated Aug. 28, 2026, with a revision date of 8/2026 that also reflects an August change to the diabetic retinopathy warning ^[2].