Thyroid Cancer Diagnoses Rise in First Year of GLP-1 RA Use

Glucagon-like peptide-1 receptor agonist (GLP-1 RA) therapy increased the risk of new thyroid cancer diagnosis within the first year of initiation, compared with other diabetic medications, although these elevations diminished in later follow-up periods.1

A secondary analysis of a retrospective target trial emulation involving nearly 352,000 adults with type 2 diabetes (T2D) at risk for cardiovascular disease (CVD) found a low absolute risk of thyroid cancer among GLP-1 RA users, with the first-year increase in diagnoses potentially linked to increased screening rates.

“The increased likelihood of thyroid ultrasonography utilization during the same period suggests a potential role for hypervigilance and increased case detection rather than true increase in the susceptibility to thyroid cancer,” wrote the investigative team, led by Rozalina G. McCoy, MD, MS, division of endocrinology, diabetes, and nutrition, department of medicine, University of Maryland School of Medicine.

GLP-1 RA use is rising in the US and worldwide given the increasing prevalence of T2D and obesity, with proven benefits for cardiovascular, kidney, and hepatitis steatosis outcomes. A potential link between GLP-1 RA use and thyroid cancer has been reported in rodents, with the US Food and Drug Administration (FDA) warning those with a personal or family history of medullary thyroid cancer against its use.2

However, the association between GLP-1 RA use and thyroid cancer in human populations has been inconclusive in the available literature, with McCoy and colleagues noting it critical to investigate further this potential link.3 The team leveraged linked administrative claims data from commercial, Medicare Advantage, and Medicare fee-for-service plans in the US to compare the effects of GLP-1 RAs, sodium-glucose cotransporter 2 inhibitors (SGLT2is), dipeptidyl peptidase-4 inhibitors (DPP4is), or sulfonylurea on rates of thyroid cancer diagnoses.1

Adults with T2D at moderate risk for CVD, and without a history of thyroid cancer, who had recently filled a prescription for these drugs between January 2014 and December 2021 were eligible for enrollment. Analyses weighed the risk of incident thyroid cancer diagnosis in patients initiating a GLP-1 RA versus any of the 3 other medications, and the risk of incident thyroid cancers between each medicine individually, between February and October 2024.

Among 351,913 patients, with a mean age of 65.3 years and 173,291 (49.3%) females, 41,112 initiated treatment with GLP-1 RA therapy. The rest of the population initiated treatment with DPP4s (n = 76, 093), SGLT2is (n = 43,499), or sulfonylurea therapy (n = 191,209).

Analyses showed the total number diagnosed with thyroid cancer was 69 (0.17%) in the GLP-1 RA cohort, 172 (0.23%) in the DPP4i cohort, 71 (0.17%) in the SGLT2 inhibitor cohort, and 381 (0.20%) in the sulfonylurea cohort. In the primary modified intention-to-treat (mITT) analysis, GLP-1 initiation was not significantly correlated with an elevated overall risk for thyroid cancer, compared with the other drug classes (hazard ratio [HR], 1.24; 95% CI, 0.88–1.76).

In the initial year of follow-up, however, McCoy and colleagues identified a significantly higher risk of thyroid cancer after GLP-1 RA initiation, compared with the non-GLP-1 RA medications (HR, 1.85; 95% CI, 1.11–3.08). After the initial year of GLP-1 use, the risk lessened during years 1 to 2 (HR, 1.27; 95% CI, 0.60–2.74) and ≥2 years of treatment exposure (HR, 0.78; 95% CI, 0.43–1.42).

Further analysis found a link between GLP-1 use and risk of thyroid cancer in the overall as-treated analysis (HR, 2.07; 95% CI, 1.10–3.95), which censored patients when therapy was discontinued or another medication was added. Overall, McCoy and colleagues noted these analyses suggested “low confidence” in a causal link between thyroid cancer and GLP-1 RAs, particularly given the timeline of the association.

“Patients treated with GLP-1RA had higher thyroid ultrasonography utilization at 6 and 12 months compared to those receiving non−GLP-1RA medications, suggesting that detection bias was behind the increased cancer diagnosis rate observed among patients treated with a GLP-1RA within the first year of therapy,” they wrote.

References

1. Brito JP, Herrin J, Swarna KS, et al. GLP-1RA Use and Thyroid Cancer Risk. JAMA Otolaryngol Head Neck Surg. Published online January 23, 2025. doi:10.1001/jamaoto.2024.4852
2. ElSayed NA, Aleppo G, Aroda VR, et al. 9. Pharmacologic Approaches to Glycemic Treatment: Standards of Care in Diabetes-2023. Diabetes Care. 2023;46(Suppl 1):S140-S157. doi:10.2337/dc23-S009
3. Bezin J, Gouverneur A, Pénichon M, et al. GLP-1 Receptor Agonists and the Risk of Thyroid Cancer. Diabetes Care. 2023;46(2):384-390. doi:10.2337/dc22-1148