Aug. 21, 2025
Glucagon-like peptide 1 receptor agonists (GLP-1RAs) are cornerstone therapies for type 2 diabetes, obesity and cardiovascular health. Their widespread use, however, has been accompanied by a persistent clinical question regarding thyroid cancer. This concern stems from rodent studies showing an increase in medullary thyroid cancer (MTC), which led to a Food and Drug Administration (FDA) warning against their use in patients with a personal or family history of MTC or multiple endocrine neoplasia, type 2 (MEN2). Previous human evidence has been inconclusive, leaving clinicians seeking definitive real-world data to guide patient care.
Robust, real-world study finds no overall increase in long-term risk
A new study published in JAMA Otolaryngology — Head & Neck Surgery provides much-needed clarity. This prespecified secondary analysis used a robust target trial emulation design, leveraging a large, diverse U.S. claims database of over 351,000 adults with type 2 diabetes. By using sophisticated statistical methods to mimic a randomized trial, the study compared patients newly starting a GLP-1RA with those initiating other common glucose-lowering drugs, known as SGLT-2 inhibitors, DPP-4 inhibitors or sulfonylureas, minimizing the potential for confounding that has plagued previous research.
The primary finding offers significant reassurance: In the main modified intention-to-treat analysis, there was no statistically significant increase in the overall risk of a thyroid cancer diagnosis for patients starting a GLP-1RA. The hazard ratio (HR) was 1.24, but with a 95% confidence interval (CI) of 0.88 to 1.76, indicating the result was not statistically significant. Furthermore, the absolute risk was low, with a thyroid cancer diagnosis occurring in only 0.17% of the 41,112 patients who initiated GLP-1RA therapy.
The first-year anomaly: Unpacking a transient signal
However, the overall result did not tell the full story. The analysis revealed that the risk was not constant over time, prompting a deeper, time-stratified investigation. This uncovered the study's most critical finding: a transient spike in diagnoses limited to the first year of therapy. During the initial 12 months, the risk of a new thyroid cancer diagnosis was significantly elevated (HR, 1.85; 95% CI, 1.11 to 3.08). Crucially, this elevated risk disappeared in subsequent years, with no significant association found between 1 to 2 years or after two years of follow-up. This front-loaded risk profile is inconsistent with the known biology of carcinogenesis, which typically requires a longer latency period, suggesting an alternative explanation to the drug causing new cancers.
The case for detection bias: Decisive evidence
The most compelling explanation for this first-year signal is detection bias, a conclusion underscored by the study's authors. "It is biologically improbable for GLP-1RAs to induce clinically apparent tumors within months of initiation," says David Toro Tobon, M.D., an endocrinologist at Mayo Clinic in Rochester, Minnesota, and an author of the study. "Instead, our findings suggest the prominent FDA warning has created heightened vigilance, leading to more-frequent thyroid examinations for those starting these drugs."
The study provides direct evidence for this hypothesis: Patients initiating GLP-1RAs had a statistically significant higher rate of undergoing thyroid ultrasonography at both six and 12 months. By 12 months, an estimated 2.1% of GLP-1RA users had received an ultrasound, compared with only 1.5% of users of other diabetes medications. This increased surveillance likely leads to the discovery of preexisting, subclinical thyroid cancers that would have otherwise remained undetected.
Clinical takeaways: Reassurance and a reframed perspective
This research provides robust, real-world evidence to reframe the conversation around GLP-1RAs and thyroid cancer. The findings suggest the observed short-term increase in diagnoses is an artifact of increased medical surveillance, not a causal link to cancer development.
For most patients without a personal or family history of MTC or MEN2, the proven metabolic and cardiovascular benefits of GLP-1RAs appear to far outweigh what this study suggests is a surveillance-driven risk of diagnosis. Given that the increased risk appears to be an artifact of detection bias, these findings do not support implementing routine thyroid cancer screening for patients initiating GLP-1RA therapy.
When a thyroid nodule is detected in a patient on a GLP-1RA, it should be approached as a probable incidental finding, with workup and management following standard guidelines. These findings should allow clinicians to prescribe these valuable medications with greater confidence.
For more information
Brito JP, et al. GLP-1RA use and thyroid cancer risk. JAMA Otolaryngology — Head & Neck Surgery. 2025;151:243.
Refer a patient to Mayo Clinic.