From the Guidelines
GLP-1 agonists are contraindicated in patients with a personal or family history of medullary thyroid carcinoma (MTC) or Multiple Endocrine Neoplasia syndrome type 2 (MEN2), severe renal impairment, or a history of serious hypersensitivity reaction to the drug. The most recent and highest quality study, published in 2023 1, highlights the importance of cautious use of GLP-1 agonists in patients with kidney disease, as they may increase the risk of acute kidney injury. Additionally, the study notes that GLP-1 agonists may cause cholelithiasis and gallstone-related complications, and have a black box warning for the risk of thyroid C-cell tumors in rodents, with human relevance not determined.
Key Contraindications
- Personal or family history of medullary thyroid carcinoma (MTC) or Multiple Endocrine Neoplasia syndrome type 2 (MEN2)
- Severe renal impairment
- History of serious hypersensitivity reaction to the drug
- Severe gastrointestinal disease, particularly gastroparesis or inflammatory bowel disease
Cautions
- Use with caution in patients with renal impairment, with dose adjustments often required
- May increase the risk of pancreatitis, particularly in patients with a history of pancreatitis
- May cause gastrointestinal side effects, such as nausea, diarrhea, and esophageal reflux
- May increase the risk of cholelithiasis and gallstone-related complications
The 2018 study published in the Journal of the American College of Cardiology 1 also highlights the importance of cautious use of GLP-1 agonists in patients with severe renal impairment or end-stage renal disease. The 2019 study published in Circulation 1 notes that GLP-1 agonists are contraindicated in patients with a personal or family history of medullary thyroid carcinoma and in patients with multiple endocrine neoplasia syndrome type 2. However, the 2023 study 1 provides the most recent and comprehensive guidance on the contraindications and cautions for GLP-1 agonists.
From the FDA Drug Label
OZEMPIC 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 hypersensitivity to semaglutide or to any of the product components [see Warnings and Precautions (5.7)].
The contraindications of Glucagon-like peptide-1 (GLP-1) agonists, such as semaglutide, are:
- Personal or family history of medullary thyroid carcinoma (MTC) or Multiple Endocrine Neoplasia syndrome type 2 (MEN 2)
- Known hypersensitivity to semaglutide or any of the product components 2
From the Research
Contraindications of GLP-1 Agonists
The contraindications of Glucagon-like peptide-1 (GLP-1) agonists include:
- A history of medullary thyroid cancer 3
- Patients with a history of pancreatitis of a known cause should use GLP-1 receptor agonists with caution 3
- The use of GLP-1 receptor agonists may be associated with certain adverse effects, including pancreatitis, pancreatic cancer, and thyroid cancer, although several meta-analyses failed to confirm a cause-effect relation between GLP-1 receptor agonists and the development of these adverse effects 4
- GLP-1 receptor agonists are not recommended for patients with a risk of diabetic ketoacidosis, and should be avoided in patients with an estimated glomerular filtration rate of less than 60 ml per min per 1·73m2 at initiation 3
Adverse Effects
Some of the common adverse effects associated with the use of GLP-1 receptor agonists include:
- Gastrointestinal symptoms, mainly nausea 4, 5
- Injection site reactions 4
- Headache 4
- Nasopharyngitis 4
- Acute kidney injury, primarily through hemodynamic derangement due to nausea, vomiting, and diarrhea 4
- Pancreatitis, with a dose-dependent risk associated with GLP-1 agonists 6
Special Considerations
GLP-1 receptor agonists should be used with caution in patients with a history of pancreatitis, and the dose of concomitant sulphonylurea or insulin may have to be decreased to reduce the risk of hypoglycemic episodes 4