Background: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are widely used for type 2 diabetes (T2DM) and obesity, but their potential association with thyroid cancer remains a concern. This study assessed thyroid cancer risk with long-term GLP-1RA use in a large real-world cohort.

Methods: We conducted a propensity score matched cohort study using electronic health records from TriNetX, including 89,646 adults with T2DM who initiated GLP-1RA therapy between 2014 and 2020, and demonstrated continued use for at least 1 year. Active comparator controls included users of insulin, metformin, sodium-glucose transporter-2 inhibitors, dipeptidyl peptidase-4 inhibitors, sulfonylureas, and thiazolidinediones. The primary outcome was the incidence of thyroid cancer.

Results: During a median follow-up of 4.5 ± 2.3 years, GLP-1RA use was not associated with an increased risk of thyroid cancer compared with any of the other antidiabetic medications. As expected, GLP-1RA use was associated with a greater reduction in HbA1c levels, while the negative control outcome remained unaffected. Findings remained consistent across subgroups stratified by sex, age, obesity-status, glycaemic-control, and GLP-1RA type and in multiple sensitivity analyses.

Conclusions: In this large real-world cohort study, long-term GLP-1RA use was not associated with an increased risk of thyroid cancer. These findings provide reassurance for the safety of GLP-1RAs and support their continued evidence-based use in clinical practice.

The authors declare no conflicts of interest.