Does Ozempic (semaglutide) cause thyroid cancer?

Ozempic (Semaglutide) and Thyroid Cancer Risk

Ozempic (semaglutide) carries a boxed warning for thyroid C-cell tumors in rodents, but there is currently no definitive evidence that it causes thyroid cancer in humans. 1

FDA Warning and Contraindications

• Semaglutide carries a black box warning regarding thyroid C-cell tumors observed in rodent studies, though human relevance has not been determined 1
• 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 (MEN2) 1, 2
• The FDA label explicitly states that routine monitoring of serum calcitonin or thyroid ultrasound is of uncertain value for early detection of MTC in patients treated with semaglutide 1

Evidence from Clinical Research

• A 2023 systematic review and meta-analysis of 37 randomized controlled trials and 19 real-world studies found no increased risk of thyroid cancer with semaglutide use compared to placebo [OR 2.04 (95% CI: 0.33-12.61); P = 0.44] 3
• Animal studies have shown dose-dependent and treatment-duration-dependent increases in thyroid C-cell tumors in mice and rats after lifetime exposure to clinically relevant plasma concentrations 1
• Cases of MTC have been reported in patients treated with liraglutide (another GLP-1 receptor agonist), but data is insufficient to establish a causal relationship between MTC and GLP-1 receptor agonist use in humans 1

Monitoring and Clinical Considerations

• Patients should be counseled about the potential risk for MTC and informed about symptoms of thyroid tumors (e.g., a mass in the neck, dysphagia, dyspnea, persistent hoarseness) 1
• Significantly elevated serum calcitonin values may indicate MTC, and patients with thyroid nodules noted on physical examination or neck imaging should be further evaluated 1
• A 2021 study of liraglutide (another GLP-1 RA) found initially elevated relative risks for thyroid cancer that were attenuated after adjusting for latency, suggesting potential surveillance bias rather than true causation 4

Other Safety Considerations with Semaglutide

• Beyond thyroid concerns, semaglutide is associated with other adverse effects including gastrointestinal disturbances (nausea, vomiting, diarrhea), risk of pancreatitis, gallbladder disease, and diabetic retinopathy complications 5, 2
• The American College of Cardiology guidelines note a 38% higher risk of serious adverse events with semaglutide versus placebo 2
• Patients with a history of diabetic retinopathy should be monitored for progression, as rapid improvement in glucose control has been associated with temporary worsening of diabetic retinopathy 1

Clinical Decision Algorithm

1. Screen for contraindications:

   • Assess for personal or family history of MTC or MEN2 (absolute contraindication) 2, 1
   • Evaluate history of pancreatitis (relative contraindication) 1

2. Counsel patients on:

   • The theoretical risk of thyroid cancer based on animal studies 1
   • Symptoms of thyroid tumors to watch for 1
   • The overall favorable risk/benefit profile for patients with type 2 diabetes 6

3. Monitor appropriately:

   • Be vigilant for symptoms of thyroid tumors 1
   • Evaluate any thyroid nodules or significantly elevated calcitonin levels 1
   • Regular monitoring for other potential adverse effects (pancreatitis, gallbladder disease, retinopathy) 5

In conclusion, while the boxed warning for thyroid C-cell tumors exists based on animal studies, current human clinical data does not demonstrate a definitive increased risk of thyroid cancer with semaglutide use. However, appropriate screening for contraindications and monitoring for symptoms remains essential.