Evaluating Thyroid Cancer Risk After GLP-1 Receptor Agonist Administration

Researchers at the Clayman Thyroid Center recently released a White Paper evaluating whether glucagon-like peptide-1 (GLP-1) receptor agonists such as semaglutide (Ozempic, Wegovy) and tirzepatide (Mounjaro, Zepbound) increased the risk of thyroid cancer in patients with type 2 diabetes and obesity.¹

The review aimed to clarify clinical misconceptions regarding the FDA boxed warning for GLP-1 receptor agonists by analyzing human clinical evidence, rodent toxicology, and institutional surgical experience. The authors found that while rodent studies showed a risk for a rare subtype of thyroid cancer, the best available human evidence did not demonstrate that GLP-1 receptor agonists caused common thyroid cancers or adversely affected existing thyroid malignancies.

Understanding the FDA Boxed Warning

The FDA boxed warning states that GLP-1 receptor agonists should not be used in patients with a history of medullary thyroid carcinoma (MTC) or Multiple Endocrine Neoplasia syndrome type 2 (MEN2). This regulatory precaution originated in rodent toxicology studies where mice and rats developed C-cell hyperplasia and tumors. Investigators noted that GLP-1 receptors were highly expressed in rodent C-cells, and chronic stimulation led to tumor formation.

However, the paper highlighted significant biological differences between species. Human C-cells expressed substantially lower levels of GLP-1 receptors compared with rodents, and downstream cellular signaling responses differed. Furthermore, human studies have not established a clinically meaningful elevation in calcitonin, a marker of C-cell activity, following the use of GLP-1 receptor agonists. This suggests that the medications do not exhibit the same C-cell stimulation in humans that was observed in animal models.

Human Clinical Evidence and Registry Data

The White Paper reviewed several large-scale studies that provided data on human risk. A Scandinavian cohort study published in BMJ analyzed national register data from Denmark, Norway, and Sweden.² The study demonstrated that GLP-1 receptor agonist use was not associated with a substantially increased risk of thyroid cancer over a mean follow-up of approximately 4 years. Similarly, an international multisite cohort analysis published in Thyroid found no evidence of increased risk across 6 population-based databases.³

A propensity-matched study using the TriNetX electronic health record (EHR) database compared GLP-1 users with those taking other agents like insulin, metformin, or SGLT2 inhibitors. The results showed no increased thyroid cancer risk compared with any of the active comparator groups. While some pharmacovigilance reports from the FDA Adverse Event Reporting System (FAERS) indicated increased reporting odds ratios, the authors noted these findings were likely influenced by media attention and label warnings rather than true incidence.

The Role of Detection Bias

The paper addressed why some studies may report an apparent association between these drugs and cancer diagnoses. In many cases, patients with cancer who were receiving GLP-1 receptor agonists had more clinical encounters, more lab monitoring, and more imaging for weight loss evaluation. Additionally, many endocrinologists who prescribed these medications routinely performed screening ultrasounds. This increased surveillance led to the discovery of pre-existing thyroid nodules and indolent cancers that might otherwise have gone undetected. The authors noted that increases in diagnoses concentrated early after starting the medication were biologically inconsistent with new cancer induction, which instead suggested detection bias.

Thyroid Cancer Subtype-Specific Analysis

Distinguishing between thyroid cancer subtypes was identified as critical for clinical decision-making. The paper highlighted that differentiated thyroid cancers, which include papillary thyroid carcinoma (PTC), follicular thyroid carcinoma (FTC), and Oncocytic (Hürthle cell) carcinoma, account for 95% to 97% of all cases. The white paper stated that the FDA warning did not apply to these common types.

In contrast, MTC arises from parafollicular C-cells and accounts for only 3% to 4% of thyroid cancers. At the Clayman Thyroid Center, which treats approximately 2000 patients with cancer annually, surgical teams have not observed a clinical association between GLP-1 exposure and MTC presentation patterns.

Clinical Recommendations for Oncologists

The authors provided a framework for clinicians navigating these treatments. GLP-1 receptor agonists, including liraglutide (Victoza, Saxenda), dulaglutide (Trulicity), and exenatide (Byetta, Bydureon), remain contraindicated in patients with a personal or family history of MTC or MEN2. However, for patients with a history of PTC, FTC, or Hürthle cell cancer, there was no contraindication to therapy.

The paper concluded that the decision to use these medications should be individualized by weighing metabolic benefits and cardiovascular risk reduction against theoretical concerns. The authors stated that GLP-1 therapy did not justify additional thyroid imaging or calcitonin testing beyond standard clinical guidelines. Having common thyroid nodules was also not considered a contraindication to starting therapy.

References

1. Clayman GL, Roy R. Do GLP-1 weight-loss shots Like Ozempic and Mounjaro really raise thyroid cancer risk? The latest facts explained. Published February 2026. Accessed February 27, 2026. https://tinyurl.com/33y9fwxx
2. Pasternak B, Wintzell V, Hviid A, et al. Glucagon-like peptide 1 receptor agonist use and risk of thyroid cancer: Scandinavian cohort study. BMJ. 2024;385:e078225. doi:10. doi:10.1136/bmj-2023-078225
3. Baxter SM, Lund LC, Andersen JH, et al. Glucagon-Like Peptide 1 receptor agonists and risk of thyroid cancer: an international multisite cohort study. Thyroid. 2025;35(1):69-78. doi:10.1089/thy.2024.0387