Can a patient with a family history of thyroid cancer, but not medullary thyroid cancer (MTC), start taking Wegovy (semaglutide) for weight loss?

Can You Start Wegovy with a Family History of Non-MTC Thyroid Cancer?

Yes, you can start Wegovy (semaglutide) in a patient with a family history of non-medullary thyroid cancer (non-MTC). The FDA contraindication for semaglutide specifically applies only to personal or family history of medullary thyroid carcinoma (MTC) or Multiple Endocrine Neoplasia syndrome type 2 (MEN 2), not other types of thyroid cancer.

FDA Contraindications Are Specific to MTC

• Semaglutide is contraindicated only 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). 1
• The black box warning stems from rodent studies showing dose-dependent thyroid C-cell tumors (adenomas and carcinomas) with semaglutide exposure, though human relevance remains undetermined. 1
• This contraindication does not extend to family history of papillary, follicular, Hürthle cell, or anaplastic thyroid cancers—which together account for approximately 95% of all thyroid malignancies. 2

Understanding the Distinction Between Thyroid Cancer Types

• MTC arises from parafollicular C-cells and accounts for only 5-8% of thyroid malignancies, with up to 75% occurring sporadically and 25% being hereditary (associated with MEN 2A, MEN 2B, or familial MTC). 2
• Differentiated thyroid cancers (papillary, follicular, Hürthle cell) arise from follicular cells and have completely different pathophysiology, genetic basis, and risk factors compared to MTC. 2
• Family history of thyroid cancer increases malignancy risk in thyroid nodules, but this refers primarily to familial syndromes associated with differentiated thyroid cancers (like PTEN Hamartoma Tumor Syndrome, not MTC/MEN 2). 2, 3

Clinical Evidence on GLP-1 RAs and Non-MTC Thyroid Cancer

• Randomized controlled trials show thyroid cancer is an infrequent event in patients receiving GLP-1 receptor agonists, with no conclusive evidence of elevated thyroid cancer risk. 4
• The biological plausibility for GLP-1 RA-associated thyroid cancer exists primarily for MTC in rodents, but is unclear for non-MTC in humans. 4
• Observational studies yield inconsistent results with low event rates, and pharmacovigilance studies show reporting signals but do not establish causality. 4

Practical Approach to Starting Wegovy

Before initiating treatment:

• Confirm the specific type of thyroid cancer in the family history—if it is papillary, follicular, Hürthle cell, or anaplastic (not MTC), proceed with Wegovy. 1
• If the family history type is unknown or uncertain, obtain clarification through medical records or family member inquiry to rule out MTC or MEN 2 syndrome. 2
• Screen for personal history of MTC by asking about symptoms: neck mass, dysphagia, dyspnea, persistent hoarseness, diarrhea, or flushing. 1

During treatment:

• Counsel patients about thyroid tumor symptoms (neck mass, dysphagia, dyspnea, persistent hoarseness) and instruct them to report these immediately. 1
• Routine monitoring with serum calcitonin or thyroid ultrasound is of uncertain value and may increase unnecessary procedures due to low test specificity. 1

Common Pitfalls to Avoid

• Do not conflate family history of differentiated thyroid cancer with the MTC contraindication—these are distinct entities with different genetic bases and risk profiles. 2
• Avoid unnecessary thyroid screening in patients on GLP-1 RAs unless clinically indicated, as this increases risk of overdiagnosis and unnecessary interventions. 1, 4
• Do not withhold beneficial GLP-1 RA therapy based on unproven thyroid cancer concerns in patients who could experience substantial metabolic and cardiovascular benefits. 4