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Zepbound ® (tirzepatide) injection
2.5 mg/ 5 mg/ 7.5 mg/ 10 mg/ 12.5 mg/ 15 mg
This information is provided in response to your request. Resources may contain information about doses, uses, formulations and populations different from product labeling. See Prescribing Information above, if applicable.
What is the incidence of pancreatitis associated with Zepbound® (tirzepatide)?
In clinical studies, 0.2% of Zepbound-treated participants had acute pancreatitis versus 0.2% of placebo-treated participants.
See important safety information, including boxed warning, in the attached prescribing information.
Prescribing Information Related to Pancreatitis
Acute pancreatitis, including fatal and non-fatal hemorrhagic or necrotizing pancreatitis, has been observed in patients treated with GLP-1 receptor agonists or tirzepatide.1
In clinical trials of tirzepatide for a different indication, 14 events of acute pancreatitis were confirmed by adjudication in 13 tirzepatide-treated patients (0.23 patients per 100 years of exposure) versus 3 events in 3 comparator-treated patients (0.11 patients per 100 years of exposure).1
In pool of SURMOUNT-1 and -2, 0.2% of tirzepatide-treated patients had acute pancreatitis confirmed by adjudication (0.14 patients per 100 years of exposure) versus 0.2% of placebo-treated patients (0.15 patients per 100 years of exposure).1
Tirzepatide has not been studied in patients with a prior history of pancreatitis. It is unknown if patients with a history of pancreatitis are at higher risk for development of pancreatitis on tirzepatide.1
Warnings and Precautions
After initiation of tirzepatide, observe patients carefully for signs and symptoms of pancreatitis (including persistent severe abdominal pain, sometimes radiating to the back, which may or may not be accompanied by vomiting).1
If pancreatitis is suspected,
- discontinue tirzepatide, and
- initiate appropriate management.1
If the diagnosis of pancreatitis is confirmed, tirzepatide should not be restarted.1
Pancreatitis Reported in Phase 3 Obesity Studies
The SURMOUNT clinical trial program assessed the efficacy and safety of tirzepatide as an adjunct to a reduced-calorie diet and increased physical activity for chronic weight management in adults with obesity or overweight in the presence of at least one weight-related comorbid
condition (hypertension, dyslipidemia, obstructive sleep apnea, cardiovascular disease, prediabetes, or T2D). Confirmed adjudicated pancreatitis events from the SURMOUNT-1 to -4 clinical trials are summarized in Adjudication-Confirmed Pancreatitis in Phase 3 SURMOUNT-1 to -4 Studies.2-5
Event, n (%)a |
Tirzepatide 5 mg |
Tirzepatide 10 mg |
Tirzepatide 15 mg |
Tirzepatide MTD |
Placebo |
SURMOUNT-1 |
1 (0.2) |
1 (0.2) |
1 (0.2) |
NA |
1 (0.2) |
SURMOUNT-2 |
NA |
0 |
2 (1%) |
NA |
1 (<1%) |
SURMOUNT-3 |
NA |
1 (0.3) |
1 (0.3) |
||
SURMOUNT-4b |
NA |
0 |
0c |
||
Abbreviations: MTD = maximum tolerated dose (10 or 15 mg); NA = not applicable.
aData are n (%); Safety analyses included all randomly assigned participants who took at least 1 dose of study drug with data from the start of the treatment to end of safety follow-up period.
bData is for the randomized treatment period week 36-88. There were no reported cases of adjudicated pancreatitis in the open label period (Week 0-36) for participants receiving tirzepatide.
cPatients in this group received tirzepatide in the open-label lead-in period.
Pancreatitis From Tirzepatide Postmarketing Data
The preferred terms pancreatitis and pancreatitis acute have been very rarely reported in the Global Patient Safety (GPS) spontaneous database.6
Very rarely is defined as an adverse event that has been reported at an estimated rate of <0.01% according to the GPS database.6
These data do not represent the rate of occurrence of an adverse event in the treated population; they merely represent the rate of reporting of a particular adverse event to the company.6
Spontaneous reporting of adverse events can be highly variable and is not controlled clinical information on which to base an assessment of whether a particular drug product caused an event.6
Spontaneous reporting is also limited in usage due to a bias in reporting, including
- incomplete information concerning the patient as with an unknown medical history
- unknown concomitant medications and disease states, and
- under reporting.6
The GPS database may also include reports of adverse events for products that may be available from Eli Lilly and Company and from other manufacturers. Although verification of product manufacturer is sought, this verification is not always obtainable. The default for these cases is to include them in the GPS database.6
Due to the dynamic nature of the GPS database, this information is valid for data received through May 13, 2024.6
Date of Last Review: 11-November-2024
Enclosed Prescribing Information
References
1Zepbound [package insert]. Indianapolis, IN: Eli Lilly and Company; 2024.
2Jastreboff AM, Aronne LJ, Ahmad NN, et al; SURMOUNT-1 Investigators. Tirzepatide once weekly for the treatment of obesity. N Engl J Med. 2022;387(3):205-216. https://doi.org/10.1056/NEJMoa2206038
3Garvey WT, Frias JP, Jastreboff AM, et al; SURMOUNT-2 investigators. Tirzepatide once weekly for the treatment of obesity in people with type 2 diabetes (SURMOUNT-2): a double-blind, randomised, multicentre, placebo-controlled, phase 3 trial. Lancet. 2023;402(10402):613-626. https://doi.org/10.1016/S0140-6736(23)01200-X
4Wadden TA, Chao AM, Machineni S, et al. Tirzepatide after intensive lifestyle intervention in adults with overweight or obesity: the SURMOUNT-3 phase 3 trial. Nat Med. 2023;29(11):2909-2918. https://doi.org/10.1038/s41591-023-02597-w
5Aronne LJ, Sattar N, Horn DB, et al; SURMOUNT-4 Investigators. Continued treatment with tirzepatide for maintenance of weight reduction in adults with obesity: the SURMOUNT-4 randomized clinical trial. JAMA. 2024;331(1):38-48. https://doi.org/10.1001/jama.2023.24945
6Data on file, Eli Lilly and Company and/or one of its subsidiaries.
Date of Last Review: November 11, 2024