Zepbound labeling supplement 031 approved

The FDA approved supplement 031 to the prescribing information for Zepbound (tirzepatide) on September 25, 2025, adding a new warning about acute kidney injury tied to fluid loss and updating sections on pancreatitis risk and breastfeeding ^[1][2]. Zepbound, made by Eli Lilly, is approved for chronic weight management and for moderate to severe obstructive sleep apnea in adults with obesity ^[2].

The biggest change was a new subsection, 5.3, called "Acute Kidney Injury Due to Volume Depletion." It tells prescribers to monitor kidney function in patients who report side effects that could lead to fluid loss, especially during the early weeks of treatment and when the dose is being raised ^[1]. The postmarketing side-effects list was also updated to include acute kidney injury and worsening of chronic kidney disease, sometimes severe enough to require dialysis ^[1].

The update added numbers on pancreatitis from clinical trials. In tirzepatide studies done for a different use, doctors confirmed 14 pancreatitis events in 13 patients taking the drug, a rate of 0.23 cases per 100 patient-years, compared with three events in three patients on comparator treatment, or 0.11 cases per 100 patient-years ^[1]. In two Zepbound trials for weight loss, 0.2% of people on Zepbound had confirmed pancreatitis (0.14 cases per 100 patient-years) versus 0.2% on placebo (0.15 cases per 100 patient-years) — rates that were close to even ^[1]. In two Zepbound trials for sleep apnea, the rate was 0.84 cases per 100 patient-years for Zepbound patients and zero for placebo patients ^[1]. The postmarketing list of gastrointestinal side effects also grew to include acute, hemorrhagic, and necrotizing pancreatitis, sometimes fatal, along with ileus, a form of bowel blockage ^[1].

On breastfeeding, the label now cites a small clinical study of 11 healthy lactating adults given a single 5 mg dose. Tirzepatide was undetectable in breast milk in 164 of 171 samples tested, using a detection limit of 4 nanograms per milliliter ^[1]. The label says there is no data yet on how the drug affects breastfed infants or milk supply, and that the decision to use Zepbound while breastfeeding should weigh the benefits of breastfeeding against the mother's need for treatment ^[1].

Why it matters for patients

This update does not change who can take Zepbound or how it is dosed. Instead, it gives doctors and patients more specific information to watch for. The kidney warning reflects the fact that severe nausea, vomiting, or diarrhea, all common early side effects of Zepbound, can cause dehydration that in rare cases harms the kidneys, particularly while starting the drug or increasing the dose ^[1]. The pancreatitis numbers show the risk is not large in the weight-loss trials, where rates were similar between Zepbound and placebo, but was higher in the sleep apnea trials, a difference the label does not explain ^[1]. The lactation data is limited to a single small study and does not answer questions about long-term effects on nursing infants ^[1].

What happens next

This was not the only Zepbound label change in the pipeline. FDA records show later supplements followed: one on January 7, 2026 (SUPPL-37) added storage and syringe instructions, one on January 20, 2026 (SUPPL-2) added a warning against sharing the KwikPen device between patients, and one on February 25, 2026 (SUPPL-42) expanded warnings on severe gastrointestinal reactions and pancreatitis symptoms ^[1]. Together these updates fed into the version of the Zepbound label referenced as current through August 2026 ^[1].