Weight Loss Medications for Patients with Family History of Medullary Thyroid Carcinoma

Contraindications for GLP-1 Receptor Agonists

• The American Gastroenterological Association and other medical societies contraindicate GLP-1 receptor agonists (including semaglutide) in patients with a personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2 (MEN2) due to increased risk of thyroid C-cell tumors 1, 2
• The FDA includes a Black Box Warning for these medications due to the risk of thyroid C-cell tumors, based on animal studies 3
• The risk applies to all GLP-1 receptor agonists including semaglutide (Wegovy), liraglutide (Saxenda), and tirzepatide (Zepbound) 2

Recommended Weight Loss Medications

• The American College of Gastroenterology recommends orlistat (Xenical 120mg prescription, Alli 60mg OTC) as the safest option for patients with MTC family history, with a mechanism that inhibits pancreatic and gastric lipases, blocking absorption of about 30% of ingested fat 4
• Orlistat produces modest weight loss of approximately 3.1% at 1 year compared to placebo, with dosing at 120mg three times daily with meals containing fat, and common side effects including gastrointestinal issues such as oily spotting, flatus with discharge, fecal urgency, and fatty/oily stool 4

Clinical Approach for Patients with Family History of MTC

• The National Comprehensive Cancer Network recommends assessing MTC risk level by determining if the patient has known RET proto-oncogene mutations (associated with hereditary MTC) 5, 6
• The American Thyroid Association suggests screening for MEN2 syndromes, which include MTC, pheochromocytoma, and hyperparathyroidism (MEN2A), or characteristic clinical features (MEN2B), and familial MTC (FMTC) 6, 7, 8
• A weight management strategy should begin with comprehensive lifestyle interventions (diet, exercise, behavioral therapy), and if pharmacotherapy is needed, use orlistat as the first-line medication, while avoiding all GLP-1 receptor agonists regardless of specific formulation 1, 4

Important Considerations

• The American College of Medical Genetics and Genomics recommends that patients with family history of MTC undergo genetic counseling and testing for RET proto-oncogene mutations to determine their personal risk, and regular screening for MTC development is essential in those with confirmed genetic risk 5, 6
• The benefit of weight loss must be balanced against medication risks, particularly in high-risk genetic populations, and for patients with severe obesity where medication options are limited, bariatric surgery may be considered as an alternative to pharmacotherapy 2, 4

Common Pitfalls to Avoid

• The Endocrine Society advises to never prescribe GLP-1 receptor agonists to patients with family history of MTC, even if the patient has not been genetically tested, and to be aware that oral formulations of GLP-1 receptor agonists are not safer - the contraindication applies to all routes of administration 1, 2, 3