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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.
Does Mounjaro® (tirzepatide) cause medullary thyroid carcinoma (MTC) or C cell hyperplasia?
It is unknown whether tirzepatide causes thyroid C cell tumors, including MTC, in humans as the human relevance of tirzepatide-induced rodent thyroid C cell tumors has not been determined.
See important safety information, including boxed warning, in the attached prescribing information.
How Often Have Medullary Thyroid Carcinoma and C-cell Hyperplasia Been Observed?
Mounjaro (tirzepatide) is a glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes (T2D) for once-weekly, subcutaneous administration.1
Tirzepatide is contraindicated in people with a personal or family history of medullary thyroid carcinoma (MTC) or in patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2).1
Observations in Rodent Studies
In rats, tirzepatide causes dose-dependent and treatment duration–dependent thyroid C cell tumors at clinically relevant exposures.1
A 2-year carcinogenicity study was conducted with tirzepatide in male and female rats at doses of 0.15, 0.50, and 1.5 mg/kg (0.1-, 0.4-, and 1-fold the maximum recommended human dose [MRHD] of 15 mg once weekly based on area under the curve [AUC]) administered by subcutaneous injection twice weekly. A statistically significant increase in
- thyroid C-cell adenomas was observed in males (≥0.5 mg/kg) and females (≥0.15 mg/kg), and
- thyroid C-cell adenomas and carcinomas combined was observed in males and females at all doses examined.1
In a 6-month carcinogenicity study in rasH2 transgenic mice, tirzepatide at doses of 1, 3, and 10 mg/kg administered by subcutaneous injection twice weekly was not tumorigenic.1
Observations in Clinical Studies
It is unknown whether tirzepatide causes thyroid C cell tumors, including MTC, in humans as the human relevance of tirzepatide-induced rodent thyroid C cell tumors has not been determined.1
No clinically relevant changes in mean calcitonin levels were observed, and no cases of MTC or C-cell hyperplasia were reported in tirzepatide studies in participants with type 2 diabetes (SURPASS).2-10
Clinical Considerations
Routine monitoring of serum calcitonin or using thyroid ultrasound is of uncertain value for early detection of MTC in patients treated with tirzepatide. Such monitoring may increase the risk of unnecessary procedures due to the low test specificity for serum calcitonin and a high background incidence of thyroid disease.1
Significantly elevated serum calcitonin values may indicate MTC, and patients with MTC usually have calcitonin values >50 ng/L. If serum calcitonin is measured and found to be elevated, the patient should be further evaluated. Patients with thyroid nodules noted on physical examination or neck imaging should also be further evaluated.1
Counsel patients regarding the potential risk for MTC with the use of tirzepatide and inform them of symptoms of thyroid tumors (eg, a mass in the neck, dysphagia, dyspnea, persistent hoarseness).1
Medullary Thyroid Cancer From Tirzepatide Postmarketing Data
The preferred term medullary thyroid cancer has been reported very rarely in the Global Patient Safety (GPS) spontaneous database.10
Very rarely is defined as an adverse event that has been reported at an estimated rate of <0.01% according to the GPS database.10
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.10
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.10
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.10
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.10
Due to the dynamic nature of the GPS database, this information is valid for data received through May 13, 2024.10
Enclosed Prescribing Information
References
The published references below are available by contacting 1-800-LillyRx (1-800-545-5979).
1Mounjaro [package insert]. Indianapolis, IN: Eli Lilly and Company; 2025.
2Rosenstock 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
3Frías 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
4Ludvik 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
5Del 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
6Dahl 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
7Rosenstock 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
8Inagaki 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
9Kadowaki 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
10Data on file, Eli Lilly and Company and/or one of its subsidiaries.
Date of Last Review: January 24, 2025