GLP-1 Receptor Agonists Show Limited Direct Evidence on Thyroid Function Tests, Highlighting a Critical Gap

Glucagon-like peptide-1 (GLP-1) receptor agonists are widely used for managing type 2 diabetes and obesity. Despite their efficacy, preclinical rodent studies have raised safety concerns regarding C-cell hyperplasia, prompting questions about their impact on thyroid function. However, clinical evidence on thyroid hormone dynamics in patients using GLP-1 RAs remains sparse and inconsistent, creating a significant knowledge gap that this systematic review aimed to characterize.

This systematic review synthesized evidence on GLP-1 receptor agonists' effects on thyroid function tests. Researchers conducted a comprehensive search across PubMed, Scopus, Web of Science, and ClinicalTrials.gov for studies published from January 2021 to December 2025. Eligible studies included randomized controlled trials and observational studies evaluating thyroid function parameters in adult patients receiving GLP-1 RAs. Risk of bias was assessed using the Cochrane Risk of Bias 2 tool for RCTs and ROBINS-I for observational studies. A narrative synthesis was performed due to substantial methodological heterogeneity.

Six studies, encompassing 900,225 participants, met the inclusion criteria. These included three randomized controlled trials, two retrospective cohort studies, and one combined Mendelian randomization and cohort study. Crucially, only one of these studies directly assessed thyroid function tests. This single study reported a mild decrease in free thyroxine and slight thyroid nodule progression after 12 months of therapy. However, its Mendelian randomization analysis revealed no significant causal effect. The remaining five studies did not systematically evaluate thyroid function parameters, focusing instead on thyroid malignancy outcomes or weight loss efficacy. The large-scale cohort studies consistently demonstrated no increased risk of thyroid tumors or thyroid cancer with GLP-1 receptor agonist use.