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Mounjaro ® (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 was the incidence and severity of gastrointestinal adverse events in the SURPASS clinical trial program?
Most gastrointestinal adverse events were mild to moderate in severity, usually occurred during the dose escalation period, and decreased with continued dosing in the SURPASS studies.
See important safety information, including boxed warning, in the attached prescribing information.
Gastrointestinal Effects
Gastrointestinal events are the most common treatment-emergent adverse events (TEAEs) associated with the use of GLP-1 receptor agonists. These events are generally mild or moderate in severity, dose dependent, and mostly occur after treatment initiation and resolve or stabilize over time.1,2
The SURPASS clinical trial program in adults with type 2 diabetes had 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, or 15 mg was achieved. 3-10
The slow dose escalation scheme used in the SURPASS clinical trial program was conducted to improve tolerability of treatment and was associated with a better gastrointestinal adverse event profile than the rapid dose escalation scheme used in the phase 2 trial.4
Adverse Reactions Reported in ≥5% of Tirzepatide-Treated Adult Patients with Type 2 Diabetes from the Placebo-Controlled Trials SURPASS-1 and -5 presents common adverse reactions, not including hypoglycemia, associated with the use of tirzepatide in the pool of placebo-controlled trials SURPASS-1 and -5. These adverse reactions occurred more commonly with tirzepatide than placebo, and were mostly gastrointestinal in nature. Most reports of nausea, vomiting, and diarrhea were mild to moderate in severity and occurred during the dose escalation period and decreased with continued use.3,7,11
In the pool of seven clinical trials including SURPASS-1 to-5, SURPASS-J mono and SURPASS-J combo, the types and frequency of common adverse reactions, not including hypoglycemia, were similar to those listed in Adverse Reactions Reported in ≥5% of Tirzepatide-Treated Adult Patients with Type 2 Diabetes from the Placebo-Controlled Trials SURPASS-1 and -5.11
Adverse Reaction, %a |
Tirzepatide 5 mg |
Tirzepatide 10 mg |
Tirzepatide 15 mg |
Placebo |
Nausea |
12 |
15 |
18 |
4 |
Diarrhea |
12 |
13 |
17 |
9 |
Decreased appetite |
5 |
10 |
11 |
1 |
Vomiting |
5 |
5 |
9 |
2 |
Constipation |
6 |
6 |
7 |
1 |
Dyspepsia |
8 |
8 |
5 |
3 |
Abdominal pain |
6 |
5 |
5 |
4 |
aPercentages reflect the number of patients who reported at least 1 occurrence of the adverse reaction.
The following gastrointestinal adverse reactions were reported more frequently in tirzepatide-treated patients than placebo-treated patients (frequencies listed, respectively, as: placebo; 5 mg; 10 mg; 15 mg):
- eructation (0.4%, 3.0%, 2.5%, 3.3%)
- flatulence (0%, 1.3%, 2.5%, 2.9%)
- gastroesophageal reflux disease (0.4%, 1.7%, 2.5%, 1.7%)
- abdominal distension (0.4%, 0.4%, 2.9%, 0.8%).11
Discontinuation Due to Gastrointestinal Adverse Events
In the pool of placebo-controlled trials, a greater incidence of gastrointestinal adverse events was reported with tirzepatide than with placebo, and led to a discontinuation of treatment in
- 3.0% of patients receiving tirzepatide 5mg
- 5.4% of patients receiving tirzepatide 10mg
- 6.6% of patients receiving tirzepatide 15mg, and
- 0.4% of patients receiving placebo.11
Enclosed Prescribing Information
References
The published references below are available by contacting 1-800-LillyRx (1-800-545-5979).
1Trujillo J. Safety and tolerability of once-weekly GLP-1 receptor agonists in type 2 diabetes. J Clin Pharm Ther. 2020;45 Suppl 1(Suppl 1):43-60. https://doi.org/10.1111/jcpt.13225
2Data on file, Eli Lilly and Company and/or one of its subsidiaries.
3Rosenstock J, Wysham C, Frías JP, et al. Efficacy and safety of a novel dual GIP and GLP-1 receptor agonist tirzepatide in patients with type 2 diabetes (SURPASS-1): a double-blind, randomised, phase 3 trial. Lancet. 2021;398(10295):143-155. https://doi.org/10.1016/S0140-6736%2821%2901324-6
4Frías JP, Davies MJ, Rosenstock J, et al; SURPASS-2 Investigators. Tirzepatide versus semaglutide once weekly in patients with type 2 diabetes. N Engl J Med. 2021;385(6):503-515. https://doi.org/10.1056/NEJMoa2107519
5Ludvik B, Giorgino F, Jódar E, et al. Once-weekly tirzepatide versus once-daily insulin degludec as add-on to metformin with or without SGLT2 inhibitors in patients with type 2 diabetes (SURPASS-3): a randomised, open-label, parallel-group, phase 3 trial. Lancet. 2021;398(10300):583-598. https://doi.org/10.1016/S0140-6736(21)01443-4
6Del Prato S, Kahn SE, Pavo I, et al; SURPASS-4 Investigators. Tirzepatide versus insulin glargine in type 2 diabetes and increased cardiovascular risk (SURPASS-4): a randomised, open-label, parallel-group, multicentre, phase 3 trial. Lancet. 2021;398(10313):1811-1824. https://doi.org/10.1016/S0140-6736(21)02188-7
7Dahl D, Onishi Y, Norwood P, et al. Effect of subcutaneous tirzepatide vs placebo added to titrated insulin glargine on glycemic control in patients with type 2 diabetes: the SURPASS-5 randomized clinical trial. JAMA. 2022;327(6):534-545. https://doi.org/10.1001/jama.2022.0078
8Rosenstock J, Frías JP, Rodbard HW, et al. Tirzepatide vs insulin lispro added to basal insulin in type 2 diabetes: the SURPASS-6 randomized clinical trial. JAMA. 2023;330(17):1631-1640. https://doi.org/10.1001/jama.2023.20294
9Inagaki N, Takeuchi M, Oura T, et al. Efficacy and safety of tirzepatide monotherapy compared with dulaglutide in Japanese patients with type 2 diabetes (SURPASS J-mono): a double-blind, multicentre, randomised, phase 3 trial. Lancet. 2022;10(9):623-633. https://doi.org/10.1016/S2213-8587(22)00188-7
10Kadowaki T, Chin R, Ozeki A, et al. Safety and efficacy of tirzepatide as an add-on to single oral antihyperglycaemic medication in patients with type 2 diabetes in Japan (SURPASS J-combo): a multicentre, randomised, open-label, parallel-group, phase 3 trial. Lancet. 2022;10(9):634-644. https://doi.org/10.1016/S2213-8587(22)00187-5
11Mounjaro [package insert]. Indianapolis, IN: Eli Lilly and Company; 2025.
Date of Last Review: January 24, 2024