Abstract
Disclosure: M.J. Barnett: None. J.R. Lam: None. C. Casipit: None. Z. Azmaiparashvili: None.
Introduction: Tirzepatide is a novel medication for the management of type 2 diabetes mellitus (T2DM) and obesity, characterized as a dual GLP-1/GIP receptor agonist. Similar to GLP-1 receptor agonists, there is a black box warning for tirzepatide for a heightened risk for medullary thyroid carcinoma (MTC). Objectives: Contrary to GLP-1 receptor agonists, which have compelling post-marketing evidence for a lack of such an association, there is less data assessing the risk from tirzepatide, as it was only recently approved by the Food and Drug Administration (FDA) in 2022. As a result, the primary objective of this retrospective cohort study is to assess the risk of malignant thyroid disease in patients with T2DM (or those who are overweight/obese) and treated with tirzepatide. Methods: This study is performed as a retrospective cohort study, with collation of de-identified patient data from TiNetX Global Collaborative Network. The analysis uses two cohorts, which are defined as Cohort A: those with T2DM or overweight/obese treated with tirzepatide (n= 283, 026), and Cohort B: those with T2DM or overweight/obese not treated with tirzepatide (n = 17, 213, 014). Propensity score matching was utilized to address imbalances at baseline, resulting in a matched cohort of n = 283, 004. The primary outcome of interest was using a defined index event, analyzed over a continuous observation period from exposure to the present. Survival analysis, frequency distributions and measures of association were incorporated to identify significant differences between each cohort. Cohorts were balanced for personal history of malignant neoplasm, A1c, history of multiple endocrine neoplasia (and family history) alongside history of irradiation exposure. Results: To ensure outcome validity, patients with history of relevant thyroid conditions were excluded. Following propensity score matching and balancing of cohorts, patients treated with tirzepatide did not demonstrate a heightened risk of malignant thyroid cancer; contrarily, the results demonstrated a significant lower incidence (Relative Risk 0.348, p < 0.001; 95% CI: 0.297-0.408). Consistent trends were noted with survival analyses, noting a higher survival probability in Cohort A over the observation period. Conclusion: Despite the black box warning for thyroid carcinoma with tirzepatide, the findings from this retrospective cohort study fail to prove such an association. This is in keeping with similar studies assessing the risk of GLP-1 receptor agonists and thyroid carcinoma. With further data acquired, perhaps the black-box warning will not be renewed.
Presentation: Sunday, July 13, 2025