Exposure to GLP-1RA and Risk of Structural Progression in Differentiated Thyroid Cancer

CONTEXT: Glucagon-like peptide-1 receptor agonists (GLP-1RA) benefit patients with diabetes mellitus (DM) and obesity. While contraindicated in medullary thyroid cancer, their effect in well-differentiated thyroid cancer (DTC) remains poorly understood. OBJECTIVE: To determine the impact of GLP-1RA on risk of DTC recurrence/progression. DESIGN AND SETTING: Retrospective observational cohort study at a tertiary care center in New York. PARTICIPANTS, INTERVENTION, MAIN OUTCOME: 536 patients with DTC exposed to GLP-1RA were matched 1:1 to 536 patients with DTC never exposed to GLP-1RA by age, date of DTC diagnosis, TNM stage, body mass index (BMI), and DM. A multi-state model enabled us to assess the impact of GLP-1RA as a time-dependent variable on the transition of patients with DTC from a "no/stable disease" state to a "recurrence/progression" state. RESULTS: A total of 1072 patients, median age 49, 71% females, 54% with DM, mean BMI±SD 35±7 kg/m², 84% with AJCC Stage I disease, 58% with American Thyroid Association (ATA) intermediate or high risk of recurrence, with median GLP-1RA exposure of 16 months were followed for a median of 69 months. GLP-1RA use was not significantly associated with recurrence or progression of disease in the survival cohort (HR = 0.87, 95% CI: 0.62-1.21, p=0.39) or the entire cohort (HR= 0.75, 95%CI:0.54-1.03, p=0.07) on a multivariable model adjusted for age, ATA risk, radioactive iodine therapy, and DM. CONCLUSION: we did not find GLP-1RA to be significantly associated with recurrent/progressive DTC. Eligible patients with DTC should not be denied the cardiometabolic benefits of GLP-1RA when clinically indicated.