Written by Peter Liu
Spoon Feed
Glucagon-like peptide-1 receptor agonists (GLP1 agonists) are not conclusively linked to an increased risk of thyroid cancer in observational trials.
GLP1 agonists may not increase the risk of thyroid cancer after all
We at JournalFeed have covered GLP1 agonists as a well-established treatment for obesity, diabetes, and prevention of heart and kidney disease. Widely accepted contraindications to GLP1 agonist use include history of pancreatitis and increased risk of medullary thyroid cancer (MTC) or multiple endocrine neoplasia syndrome type 2 (MEN2). However, whether GLP1 agonists truly increase pancreatitis and thyroid cancer risk remains uncertain. For example, JournalFeed has previously highlighted evidence that GLP1 agonists may not increase pancreatitis risk.
The link between GLP1 agonists and thyroid cancer risk is also now being called into question. A recent retrospective, active-comparator, new-user cohort study adds to a growing body of observational studies and RCT meta-analyses that generally do not conclude a link between GLP1 agonists and thyroid cancer. This study evaluated the risk of incident thyroid tumors among 460,032 U.S. patients with type 2 diabetes initiating GLP-1 receptor agonists (GLP-1RAs) versus SGLT2 inhibitors, DPP-4 inhibitors, and sulfonylureas. Using propensity score adjustment and meta-analysis, no significant increase in thyroid tumor risk was found with GLP-1RA use (e.g., HR vs. DPP-4i 0.93; 95%CI 0.83–1.04).
The link between GLP1 agonists and thyroid cancer originated with preclinical rodent studies of GLP1 agonists, where a dose-dependent increase in thyroid cancer risk was noted. But human thyroid C cells have different membrane receptors than rodent cells and lack GLP1 receptors seen in rodents. Perhaps this is why there is still no conclusive evidence linking GLP1 agonists with human thyroid cancer risk, including in meta-analyses of GLP1 agonist RCTs.
How does this change my practice?
Our understanding of the safety and risks of GLP1 agonists appears to be evolving. While it still remains standard practice to avoid GLP1 agonist use in patients with history of pancreatitis or high risk of MTC and MEN2, there is now some evidence to support its use even in these populations. For me, MTC and MEN2 will remain strict contraindications to GLP1 prescribing for now. Luckily, this is a very small subset of most practices. However, with the right patient-centered counseling, I think GLP1 agonists could be reasonably prescribed for patients with a history of pancreatitis.
Source
Risk of Thyroid Tumors With GLP-1 Receptor Agonists: A Retrospective Cohort Study. Diabetes Care. 2025 Jun 4:dc250154. doi: 10.2337/dc25-0154. Epub ahead of print. PMID: 40465422
