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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.
How often were gastrointestinal adverse events reported in Zepbound® (tirzepatide) clinical studies?
Severe gastrointestinal adverse reactions were reported more frequently among patients receiving tirzepatide (1.7 to 3.1%) than placebo (1%).
See important safety information, including boxed warning, in the attached prescribing information.
Gastrointestinal Effects
Use of tirzepatide has been associated with gastrointestinal (GI) adverse reactions (ADRs), sometimes severe (see Gastrointestinal Adverse Reactions in SURMOUNT-1 and SURMOUNT-2).1
Parameter, % of patients |
Tirzepatide 5 mg |
Tirzepatide 10mg |
Tirzepatide 15 mg |
Placebo |
Severe GI ADR |
1.7 |
2.5 |
3.1 |
1 |
GI ADR |
56 |
56 |
56 |
30 |
Discontinuation due to GI ADR |
1.9 |
3.3 |
4.3 |
0.5 |
Abbreviations: ADR = adverse reaction; GI = gastrointestinal.
Tirzepatide has not been studied in patients with severe GI disease, including severe gastroparesis, and is therefore not recommended in these patients.1
The majority of nausea, vomiting, and/or diarrhea events occurred during dose escalation and decreased over time.1
In SURMOUNT-3 and SURMOUNT-4, ADRs were similar to those reported in the SURMOUNT-1 and SURMOUNT-2.1
The study design for the SURMOUNT clinical trial program included a 20-week dose escalation phase. The starting dose of tirzepatide was 2.5 mg once weekly for 4 weeks, escalated in 2.5 mg increments every 4 weeks until the assigned dose of 5, 10, 15 mg, or maximum tolerated dose (MTD) was achieved.2
The most frequently reported AEs for tirzepatide were GI in nature (Common Gastrointestinal Treatment-Emergent Adverse Events (≥5% Frequency in Any Arm)).4-7
Parameter, n (%)a |
Tirzepatide 5 mg |
Tirzepatide 10 mg |
Tirzepatide 15 mg |
Tirzepatide MTD |
Placebo |
Nausea |
|||||
SURMOUNT-1 |
155 (25) |
212 (33) |
195 (31) |
NA |
61 (10) |
SURMOUNT-2 |
NA |
63 (20) |
68 (22) |
NA |
20 (6) |
SURMOUNT-3 |
NA |
114 (40) |
41 (14) |
||
SURMOUNT-4 |
|||||
Lead-in treatment period |
NA |
278 (36) |
NA |
||
Double-blind and safety follow-up period |
NA |
27 (8) |
9 (3) |
||
Diarrhea |
|||||
SURMOUNT-1 |
118 (19) |
135 (21) |
145 (23) |
NA |
47 (7) |
SURMOUNT-2 |
NA |
62 (20) |
67 (22) |
NA |
28 (9) |
SURMOUNT-3 |
NA |
89 (31) |
27 (9) |
||
SURMOUNT-4 |
|||||
Lead-in treatment periodb |
NA |
165 (21) |
NA |
||
Double-blind and safety follow-up period |
NA |
36 (11) |
16 (5) |
||
Constipation |
|||||
SURMOUNT-1 |
106 (17) |
109 (17) |
74 (12) |
NA |
37 (6) |
SURMOUNT-2 |
NA |
25 (8) |
28 (9) |
NA |
13 (4) |
SURMOUNT-3 |
NA |
66 (23) |
20 (7) |
||
SURMOUNT-4 |
|||||
NA |
162 (21) |
NA |
|||
Vomiting |
|||||
SURMOUNT-1 |
52 (8) |
68 (11) |
77 (12) |
NA |
11 (2) |
SURMOUNT-2 |
NA |
34 (11) |
41 (13) |
NA |
10 (3) |
SURMOUNT-3 |
NA |
52 (18) |
4 (1) |
||
SURMOUNT-4 |
|||||
Lead-in treatment periodb |
NA |
128 (16) |
NA |
||
Double-blind and safety follow-up period |
NA |
19 (6) |
4 (1) |
||
Dyspepsia |
|||||
SURMOUNT-1 |
56 (9) |
62 (10) |
71 (11) |
NA |
27 (4) |
SURMOUNT-2 |
NA |
23 (7) |
22 (7) |
NA |
10 (3) |
SURMOUNT-3 |
NA |
27 (9) |
9 (3) |
||
SURMOUNT-4 |
|||||
NA |
63 (8) |
NA |
|||
Abdominal Pain |
|||||
SURMOUNT-1 |
31 (5) |
34 (5) |
31 (5) |
NA |
21 (3) |
SURMOUNT-2 |
NA |
12 (4) |
23 (7) |
NA |
7 (2) |
SURMOUNT-3 |
NA |
30 (11) |
7 (2) |
||
SURMOUNT-4 |
|||||
NA |
48 (6) |
NA |
|||
Eructation |
|||||
SURMOUNT-1 |
24 (4) |
33 (5) |
35 (6) |
NA |
4 (1) |
SURMOUNT-2 |
NA |
19 (6) |
13 (4) |
NA |
2 (1) |
SURMOUNT-3 |
NA |
16 (6) |
3 (1) |
||
Flatulence |
|||||
SURMOUNT-3 |
NA |
19 (7) |
8 (3) |
||
Gastroesophageal reflux disease |
|||||
SURMOUNT-3 |
NA |
19 (7) |
7 (2) |
||
SURMOUNT-4 |
|||||
NA |
69 (9) |
NA |
|||
Abbreviation: MTD = maximum tolerated dose (10 or 15 mg); NA = not applicable.
aData are safety 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. Note: Patients may be counted in more than 1 category.
bData are from week 0-36.
cThe majority of gastrointestinal events occurred during dose escalation and decreased over time.
A post-hoc analysis of SURMOUNT-1 data for GI ADRs showed that mean weight reduction in all treatment groups was consistent regardless of the presence or absence of GI ADRs.8
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.
2le Roux CW, Zhang S, Aronne LJ, et al. Tirzepatide for the treatment of obesity: rationale and design of the SURMOUNT clinical development program. Obesity (Silver Spring). 2023;31(1):96-110. https://doi.org/10.1002/oby.23612
3Frias JP, Nauck MA, Van J, et al. Efficacy and tolerability of tirzepatide, a dual glucose-dependent insulinotropic peptide and glucagon-like peptide-1 receptor agonist in patients with type 2 diabetes: a 12-week, randomized, double-blind, placebo-controlled study to evaluate different dose-escalation regimens. Diabetes Obes Metab. 2020;22(6):938-946. https://doi.org/10.1111/dom.13979
4Jastreboff 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
5Garvey 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
6Wadden 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
7Aronne 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
8Rubino DM, Pedersen SD, Connery L, et al. Tolerability and weight reduction of tirzepatide in adults with obesity or overweight. Abstract presented at: Obesity Week; October 14-17, 2023; Dallas, Texas.
Date of Last Review: December 24, 2025