Risk of Thyroid Cancer and Glucagon-Like Peptide 1 Receptor Agonists

According to the secondary analysis from a target trial emulation of a comparative effectiveness study, there was an increased risk of thyroid cancer diagnosis within the first year following initiation of glucagon-like peptide-1 receptor agonists (GLP-1RA) therapy when compared to other diabetes medications.

These data are the result of a prespecified secondary analysis of a target trial emulation of a comparative effectiveness study. With claims data from commercial, Medicare Advantage, and Medicare fee-for-service plans in the United States, this study included 351913 patients with type 2 diabetes at a moderate risk for cardiovascular disease who did not have any history of thyroid cancer. All patients had newly filled prescriptions for GLP-1RA (n = 41112), sodium-glucose cotransporter 2 (SGLT2) inhibitor (n = 43499), dipeptidyl peptidase-4 (DPP4) inhibitor (n = 76093), or sulfonylurea (n = 191209). Hazard ratios (HR) for thyroid ratio with use of GLP-1RA vs the other 3 drug classes were estimated by overall and piecewise by inverse propensity score weighted Coz hazard models.

There were 0.17% of patients diagnosed with thyroid cancer in the GLP-1RA group, 0.23% in the DPP4 inhibitor group, 0.17% in the SGLT2 inhibitor group, and 0.20% in the sulfonylurea group. In the modified intention-to-treat analysis, initiation on GLP-1RA was no significantly associated with an increased overall risk for thyroid cancer when compared with the other drugs (HR, 1.24). Within the first year of GLP-1RA initiation, however, the risk for thyroid cancer was significantly higher (HR, 1.85). This increased risk was amplified in the overall as-treated analysis (HR, 2.07), which censored patients upon discontinued of therapy or addition of another medication.

Dr Brito et al concluded while there is a low total risk of thyroid cancer among patients receiving GLP-1RA therapy, “there was an increased risk of new thyroid cancer diagnosis within the first year of GLP-1RA initiation compared to 3 other diabetes drugs.” They went on to note this association is “likely due to increased vigilance and case detection rather than de novo pathogenesis,” as the increased risk was only apparent in the first year following GLP-1RA initiation.

Source:

Brito JP, Herrin J, Swarna KS, et al. GLP-1RA use and thyroid cancer risk. JAMA Otolaryngol Head Neck Surg. January 23, 2025. doi: 10.1001/jamaoto.2024.4852