Is History of Medullary Thyroid Cancer a Contraindication for Ozempic?
Yes, a personal or family history of medullary thyroid carcinoma (MTC) is an absolute contraindication to Ozempic (semaglutide), as explicitly stated in the FDA black box warning and prescribing information. 1
FDA Black Box Warning and Absolute Contraindication
The FDA prescribing information for Ozempic clearly states that the medication is contraindicated in patients with:
- A personal or family history of medullary thyroid carcinoma (MTC) 1
- Multiple Endocrine Neoplasia syndrome type 2 (MEN 2) 1
This contraindication stems from rodent studies showing dose-dependent and treatment-duration-dependent thyroid C-cell tumors at clinically relevant exposures, though human relevance remains uncertain. 1
Guideline Society Consensus
Multiple major guideline societies uniformly recommend avoiding semaglutide in patients with personal or family history of MTC:
The American College of Cardiology explicitly lists "history of MEN2 or medullary thyroid cancer" as a reason to consider alternative agents when selecting GLP-1 receptor agonists. 2
The American Gastroenterological Association and other medical societies contraindicate all GLP-1 receptor agonists (including semaglutide, liraglutide, and tirzepatide) in patients with personal or family history of MTC or MEN2 due to increased risk of thyroid C-cell tumors. 3
The Endocrine Society advises never prescribing GLP-1 receptor agonists to patients with family history of MTC, even if the patient has not been genetically tested. 3
Clinical Implications and Patient Counseling
For patients requiring diabetes management or weight loss who have MTC history:
Counsel all patients starting semaglutide about potential MTC risk and inform them of thyroid tumor symptoms (neck mass, dysphagia, dyspnea, persistent hoarseness). 1
Note that routine monitoring of serum calcitonin or thyroid ultrasound is of uncertain value for early detection of MTC in patients treated with Ozempic. 1
For patients with family history of MTC requiring weight loss medication, orlistat is recommended as the safest alternative option. 3
Important Caveats
The contraindication applies universally across all formulations:
- Oral formulations of GLP-1 receptor agonists are not safer—the contraindication applies to all routes of administration. 3
- This restriction applies to all GLP-1 receptor agonists, not just semaglutide. 3
For patients with family history of MTC:
- The American College of Medical Genetics and Genomics recommends genetic counseling and testing for RET proto-oncogene mutations to determine personal risk. 3
- Regular screening for MTC development is essential in those with confirmed genetic risk. 3
Evidence regarding non-medullary thyroid cancer:
- While the black box warning specifically addresses MTC, evidence from randomized trials shows thyroid cancer as a rare event overall, with no conclusive evidence of elevated risk for non-MTC. 4
- The SUSTAIN-6 and PIONEER-6 cardiovascular outcome trials did not show increased rates of any thyroid cancer, though follow-up duration may be insufficient. 5