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. 2025 Mar 1;151(3):243-252.
doi: 10.1001/jamaoto.2024.4852.

GLP-1RA Use and Thyroid Cancer Risk

Juan P Brito  1   2 , Jeph Herrin  3 , Kavya Sindhu Swarna  4   5 , Naykky M Singh Ospina  6 , Victor M Montori  1   2 , David Toro-Tobon  1   2 , Guillermo E Umpierrez  7 , Rodolfo J Galindo  8 , Yihong Deng  4   5 , Mindy M Mickelson  4 , Hui Shao  9   10 , Eric C Polley  11 , Rozalina G McCoy  5   12   13
Affiliations

GLP-1RA Use and Thyroid Cancer Risk

Juan P Brito et al. JAMA Otolaryngol Head Neck Surg. .

Abstract

Importance: The increasing use of glucagon-like peptide-1 receptor agonists (GLP-1RA) demands a better understanding of their association with thyroid cancer.

Objective: To estimate the risk of incident thyroid cancer among adults with type 2 diabetes being treated with GLP-1RA vs other common glucose-lowering medications.

Design, setting, and participants: This was a prespecified secondary analysis of a target trial emulation of a comparative effectiveness study using claims data for enrollees in commercial, Medicare Advantage, and Medicare fee-for-service plans across the US. Eligible participants were adults with type 2 diabetes at moderate risk for cardiovascular disease and without history of thyroid cancer who had newly filled prescriptions for GLP-1RA, sodium-glucose cotransporter 2 inhibitor (SGLT2i), dipeptidyl peptidase-4 inhibitor (DPP4i), or sulfonylurea from January 1, 2014, to December 31, 2021. Data were analyzed February 1 to October 31, 2024.

Main outcomes and measures: Overall and piecewise (<1, 1-2, and ≥2 years since treatment initiation) hazard ratios (HRs) for thyroid cancer with use of GLP-1RA vs the other 3 drug classes were estimated using inverse propensity score weighted Cox proportional hazards models. Modified intention-to-treat (mITT) (primary) and as-treated (sensitivity) analyses were performed.

Results: Of 351 913 patients (mean [SD] age, 65.3 [8.5] years; 173 391 [49.3%] females and 178 522 [50.7%] males), 41 112 started treatment with GLP-1RA; 76 093, with DPP4i; 43 499, with SGLT2i; and 191 209, with sulfonylurea therapy. The numbers of patients diagnosed with thyroid cancer were 69 (0.17%) in the GLP-1RA group, 172 (0.23%) in the DPP4i group, 72 (0.17%) in the SGLT2i group, and 381 (0.20%) in the sulfonylurea group. In the mITT analysis, GLP-1RA initiation was not significantly associated with increased overall risk for thyroid cancer compared to the other 3 diabetes drugs (HR, 1.24; 95% CI, 0.88-1.76). However, the risk for thyroid cancer was significantly higher within the first year after GLP-1RA initiation (HR, 1.85; 95% CI, 1.11-3.08) and was amplified in the overall as-treated analysis that censored patients when therapy was discontinued or another medication was added (HR, 2.07; 95% CI, 1.10-3.95).

Conclusions and relevance: This secondary analysis of a target trial emulation of a comparative effectiveness study found that despite the low absolute risk of thyroid cancer among patients receiving GLP-1RA therapy, there was an increased risk of new thyroid cancer diagnoses within the first year of GLP-1RA initiation compared to 3 other diabetes drugs. This finding may have been due to enhanced early detection; therefore, further research is necessary to understand the underlying causes of this association.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Umpierrez reported grants from Dexcom and Abbott and serving on the advisory boards of GlyCare and Dexcom outside the submitted work. Dr Galindo reported grants from Novo Nordisk and consulting/advisory fees from Eli Lilly and Novo Nordisk outside the submitted work. Dr McCoy reported grants from the US National Institute of Diabetes and Digestive and Kidney Diseases, National Institute on Aging, and the American Diabetes Association, and personal fees from the American Diabetes Association, Yale New Haven Health System, and EmmiEducate outside the submitted work. No other disclosures were reported.

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