Evaluating Thyroid Cancer Risk in Glucagon-like Peptide-1 Analog Users With Thyroid Nodules.

INTRODUCTION: Thyroid nodules are common and require vigilant monitoring due to malignancy potential. They become particularly concerning in patients using glucagon-like peptide (GLP-1) analogs, which are associated with a proposed increased risk of medullary thyroid cancer. This study aims to evaluate the incidence of thyroid cancer in patients with thyroid nodules treated with GLP-1 analogues. METHODS: We conducted a retrospective cohort study using the TriNetX database looking at pediatric and adult patients diagnosed with thyroid nodules (ICD-10-CM E04) and treated with GLP-1 analogues (ATC A10BJ) from 1995 to 2024. In addition, we compared the GLP-1 cohort to a cohort of patients who developed thyroid nodules after starting metformin. Demographic data and biochemical markers were assessed. The primary outcome was the incidence of thyroid cancer, identified by the first occurrence of ICD-10-CM C73 following the diagnosis of thyroid nodules and the start of GLP-1 analogues. Descriptive statistics summarized baseline characteristics, and Kaplan-Meier survival analysis estimated the cumulative incidence of thyroid cancer. Analyses were performed using the TriNetX Analytics platform, with statistical significance defined as P < 0.05. RESULTS: We identified 1,401,568 patients using GLP-1 analogues and 2,779,340 patients with thyroid nodules in our database. Among these, 171,460 patients had both conditions, with 98,142 (57%) developing thyroid nodules after starting GLP-1 analogues. The average age of the GLP-1 cohort was 60 ± 13 years, with 72% (n = 66,195) being female and 66% (n = 60,855) identifying as White. Kaplan-Meier analysis indicated that the survival probability, or the likelihood of not developing thyroid cancer by the end of the study, was 91.042% for the GLP-1 cohort, with 4687 cases of thyroid cancer observed. In comparison, the metformin cohort (n = 306,114) had a higher survival probability of 94%, with 11,898 cases of thyroid cancer observed. The risk ratio of 0.99 (95% confidence interval: 0.96-1.03) between the cohorts indicates no significant difference in the risk of developing thyroid cancer for patients on GLP-1 analogues compared to those on metformin. CONCLUSIONS: Our study indicates a relatively low incidence of thyroid cancer among patients with thyroid nodules treated with GLP-1 analogues.