You are now leaving the Lilly Medical website
The link you clicked on will take you to a site maintained by a third party, which is solely responsible for its content. Lilly USA, LLC does not control, influence, or endorse this site, and the opinions, claims, or comments expressed on this site should not be attributed to Lilly USA, LLC. Lilly USA, LLC is not responsible for the privacy policy of any third-party websites. We encourage you to read the privacy policy of every website you visit.
Click "Continue" to proceed or "Return" to return to Lilly Medical
If you wish to report an adverse event or product complaint, please call 1-800-LILLYRX (1-800-545-5979)
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 injection site reactions associated with Zepbound® (tirzepatide) in the SURMOUNT studies?
Injection site reactions were reported in 2.1% to 11.1% of SURMOUNT study participants treated with tirzepatide.
See important safety information, including boxed warning, in the attached prescribing information.
Injection Site Reactions
In Zepbound (tirzepatide)-treated patients in a pool of SURMOUNT-1 and SURMOUNT-2, injection site reactions were more frequent in those with anti-tirzepatide antibodies (11.3%) compared to those who did not develop anti-tirzepatide antibodies (1%).1
Injection Site Reactions Reported in SURMOUNT Studies
Injection site reactions in tirzepatide only treated patients ranged from 2.1% to 11.1% in the SURMOUNT-1 to -4 studies and occurred more commonly than placebo as shown in Number of Participants Who Reported Injection Site Reactions in SURMOUNT Studies. None of the injection site reactions were reported as severe or serious.2-6
Parameter, n (%)a |
Tirzepatide 5 mg |
Tirzepatide 10 mg |
Tirzepatide 15 mg |
Tirzepatide Open-Label Lead-In Period |
Tirzepatide MTD |
Placebo |
SURMOUNT-1b |
18 (2.9) |
36 (5.7) |
29 (4.6) |
NA |
NA |
2 (0.3) |
SURMOUNT-2c |
NA |
9 (2.9) |
7 (2.3) |
NA |
NA |
0 |
SURMOUNT-3d |
NA |
NA |
32 (11.1) |
3 (1.0) |
||
SURMOUNT-4e |
NA |
7 (2.1) |
2 (0.6)h |
|||
Abbreviations: MTD = maximum tolerated dose (10 or 15 mg); NA = not applicable.
aSafety analysis set: safety analysis set 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.
bSafety analysis set: data obtained during the treatment period plus safety follow-up period from mITT, regardless of adherence to study drug.
cSafety analysis set: data obtained during the treatment period plus safety follow-up period from the ITT population, regardless of adherence to study drug or initiation of rescue antihyperglycemic medication.
dSafety analysis set: data obtained starting after the first dose of study treatment and ended at the end of study period including off-drug follow-up visit.
eSafety analysis set: data obtained starting after randomization visit and ended after whole study period including off-drug follow-up visit.
fAdverse events during the tirzepatide lead-in period from Week 0 to Week 36.
gSafety analysis set defined as all participants who were assigned to open-label tirzepatide treatment. The safety follow-up period was included for participants who discontinued during the open-label period.
hPatients in this group received tirzepatide in the open-label lead-in period.
In the SURMOUNT-5 study, a 72-week, phase 3b, open-label, randomized controlled trial comparing tirzepatide (10 mg or 15 mg) with semaglutide (1.7 mg or 2.4 mg) in adults with obesity but without type 2 diabetes, injection site reactions were more common in the tirzepatide group (8.6%, n=32) compared with the semaglutide group (0.3%, n=1).7
No patients experienced severe or serious injection site reactions, nor did any discontinue trial treatment because of such reactions.7
Management of Injection Site Reactions
There is no information available regarding injection site reactions that worsen over time in patients taking tirzepatide for weight management.
The SURMOUNT study protocols did not provide guidance about the management of injection site reactions. During the studies, investigators used local standards of care to make treatment recommendations.2-5
Eli Lilly and Company cannot provide treatment recommendations for injection site reactions. The treating health care provider may use the information provided, the patient’s prior medical history and concomitant medications, and other individual factors in developing a treatment plan. The treating health care provider should consider potential risks and benefits of treatment options and monitor appropriately.
Enclosed Prescribing Information
References
The published references below are available by contacting 1-800-LillyRx (1-800-545-5979).
1Zepbound [package insert]. Indianapolis, IN: Eli Lilly and Company; 2025.
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.
7Aronne LJ, Horn DB, le Roux CW, et al; SURMOUNT-5 Trial Investigators. Tirzepatide as compared with semaglutide for the treatment of obesity. N Engl J Med. 2025;393:26-36. https://www.doi.org/10.1056/NEJMoa2416394
Date of Last Review: December 17, 2025