A secondary analysis of a comparative effectiveness study found that use of glucagon-like peptide-1 receptor agonists among patients with type 2 diabetes was associated with a higher risk of thyroid cancer diagnoses within the first year of treatment—likely due to enhanced early detection rather than de novo carcinogenesis.
The target trial emulation study analyzed data from approximately 352,000 adults with type 2 diabetes at moderate cardiovascular risk and with no prior thyroid cancer history. Patients were prescribed one of four diabetes medications between 2014 and 2021: glucagon-like peptide-1 receptor agonists (GLP-1RA; n = 41,112), dipeptidyl peptidase-4 inhibitors (n = 76,093), sodium-glucose cotransporter-2 inhibitors (n = 43,499), or sulfonylureas (n = 191,209).
The primary outcome was the risk of thyroid cancer diagnosis, assessed using modified intention-to-treat (mITT) and as-treated analyses. Results of the analysis were published in JAMA Otolaryngology–Head & Neck Surgery.
In the mITT analysis, there was no significant overall increase in thyroid cancer risk associated with starting GLP-1RAs compared to the other three classes of drugs (hazard ratio [HR] = 1.24, 95% confidence interval [CI] = 0.88–1.76); however, there was a higher risk within the first year of treatment receipt (HR = 1.85, 95% CI = 1.11–3.08). This risk was also heightened in the as-treated analysis, which accounted for treatment discontinuation or switching (HR = 2.07, 95% CI, 1.10–3.95). There was no increased risk after 2 years of therapy.
Study authors attributed the increased cancer risk to greater medical scrutiny rather than a biological effect.
"The increased likelihood of thyroid ultrasonography utilization during the same period suggests a potential role for hypervigilance and increased case detection rate rather than true increase in the susceptibility to thyroid cancer," wrote first study author Juan P. Brito, MD, of the Division of Endocrinology, Diabetes, Metabolism, and Nutrition at the Mayo Clinic in Rochester, Minnesota, and colleagues.
Although the study does not establish a causal link between GLP-1RA treatment and thyroid cancer, it highlights the need for continued post-market surveillance of these widely used diabetes and weight-loss drugs. Further research is needed to explore potential biological mechanisms underlying GLP-1RAs' effects on thyroid neoplasia.
The study was funded by the Patient-Centered Outcomes Research Institute (PCORI). Some authors reported grants or advisory roles with Novo Nordisk, Eli Lilly, and the American Diabetes Association, but no conflicts of interest were noted regarding the study findings.
