Semaglutide, Other GLP-1 Receptor Agonists, and Papillary Thyroid Carcinoma: A Narrative Review of Risk, Progression, and Mechanisms

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Abstract

Semaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1RA), is widely prescribed for type 2 diabetes and obesity. Rodent studies showed thyroid C-cell tumors, prompting a boxed warning for medullary thyroid carcinoma (MTC); whether this extends to papillary thyroid carcinoma (PTC), a follicular-cell-derived tumor, is uncertain. This narrative review examines semaglutide and other GLP-1RAs in relation to PTC, distinguishing semaglutide-specific from class-level evidence, and PTC from differentiated thyroid cancer (DTC), MTC, and thyroid cancer overall. Most human studies evaluated GLP-1RAs as a class and reported thyroid cancer overall; semaglutide-specific and PTC-specific estimates are scarce. Pooled trials and national cohorts mostly showed no statistically significant increase in thyroid cancer, although three separate meta-analyses of randomized trials each reported a statistically significant increase in overall thyroid cancer, and case-control and spontaneous-reporting studies reported signals vulnerable to detection bias and confounding. In a matched cohort of 1072 patients with DTC, GLP-1RA exposure (median 16 months) was not significantly associated with progression over 69 months. Receptor-expression findings were inconsistent, and preclinical data did not show proliferative effects. The cohort and progression findings indicate no statistically detectable increase within the available sample sizes, exposure durations, and event numbers; they do not establish oncological safety. Semaglutide-specific, histology-resolved studies with longer exposure are needed.

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