From the Guidelines
Tirzepatide and semaglutide are contraindicated in patients with a personal or family history of medullary thyroid carcinoma (MTC) or in patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2). Both medications should be avoided in patients with a history of serious hypersensitivity reactions to the drugs or their components. These medications are not recommended for patients with a history of pancreatitis unless the benefits clearly outweigh the risks. Caution should be exercised in patients with diabetic retinopathy, as rapid improvement in glucose control may worsen retinopathy temporarily. These medications should be used cautiously in patients with severe gastrointestinal disease, including gastroparesis, as they delay gastric emptying. They are not recommended during pregnancy or breastfeeding due to insufficient safety data. In patients with renal impairment, dose adjustments may be necessary, particularly for tirzepatide in severe renal impairment. These contraindications exist because these GLP-1 receptor agonists (semaglutide) and dual GIP/GLP-1 receptor agonists (tirzepatide) have been associated with thyroid C-cell tumors in rodent studies, though the human relevance is unknown, and their effects on gastrointestinal motility can exacerbate existing GI conditions 1.
Some key points to consider when prescribing tirzepatide and semaglutide include:
- Monitoring for signs of pancreatitis, such as abdominal pain and elevated pancreatic enzymes
- Regular assessment of renal function, particularly in patients with pre-existing kidney disease
- Counseling patients on the potential risks and benefits of these medications, including the risk of thyroid C-cell tumors and gastrointestinal side effects
- Adjusting doses or discontinuing the medication if adverse effects occur or if the patient's condition changes.
It is essential to weigh the potential benefits of these medications against the potential risks and to carefully monitor patients for any adverse effects. The most recent and highest-quality study, published in 2025, provides guidance on the use of these medications in patients with type 2 diabetes and highlights the importance of careful patient selection and monitoring 1.
From the FDA Drug Label
MOUNJARO is contraindicated in patients with: A personal or family history of medullary thyroid carcinoma (MTC) or in patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2) [see Warnings and Precautions (5.1)]. Known serious hypersensitivity to tirzepatide or any of the excipients in MOUNJARO.
The contraindications to tirzepatide are:
- A personal or family history of medullary thyroid carcinoma (MTC) or in patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2)
- Known serious hypersensitivity to tirzepatide or any of the excipients in MOUNJARO. There is no information about semaglutide in the provided drug labels. 2, 2, 2
From the Research
Contraindications to Tirzepatide and Semaglutide
- Contraindications for semaglutide include:
- Contraindications for tirzepatide are not explicitly stated in the provided studies, but as a dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist, it may share similar contraindications with semaglutide
- Additionally, semaglutide is not recommended in patients with suspected or confirmed pancreatitis, and is not indicated in type 1 diabetes 3
- The use of GLP-1 receptor agonists, including tirzepatide and semaglutide, may be associated with an increased risk of thyroid cancer, particularly medullary thyroid cancer 4
Warnings and Precautions
- Patients with a history of pancreatitis should not use semaglutide, and the use of tirzepatide in these patients has not been studied 3
- GLP-1 receptor agonists, including tirzepatide and semaglutide, may cause gastrointestinal adverse events, such as nausea, diarrhea, and vomiting 3, 5, 6
- The administration of oral semaglutide requires careful instruction to minimize the risk of gastrointestinal adverse events, including taking the tablet on an empty stomach with a limited amount of water, and waiting at least 30 minutes before eating, drinking, or taking other oral medications 3