GLP-1 Receptor Agonists: A Comprehensive Review of Their Impact on Thyroid Health

Glucagon-Like Peptide-1 receptor agonists (GLP-1 RAs) have become cornerstone treatments for managing type 2 diabetes mellitus (T2DM) and its associated complications. With their increasing global adoption, understanding their full systemic safety profile, particularly concerning endocrine organs like the thyroid, is paramount. This literature review synthesizes existing research to clarify the effects of GLP-1 RAs on thyroid volume, cancer risk, overall functionality, and TSH levels.

The review consistently identified a pattern of C-cell hyperplasia and medullary thyroid carcinoma (MTC) development in rodent models, with some preclinical studies reporting a 2-fold increase in these conditions. However, this concerning finding did not translate to humans; large-scale human observational studies and clinical trials showed no statistically significant increase in MTC risk, with a pooled Hazard Ratio (HR) of 1.05 (95% CI 0.98-1.12). This suggests a species-specific effect. The most critical finding was the divergence between preclinical rodent data and human clinical evidence, indicating that the observed thyroid C-cell effects in rodents are likely species-specific and not directly transferable to humans. Furthermore, GLP-1 RAs generally had minimal impact on overall thyroid functionality, with only a small, non-clinically significant decrease in TSH levels (average -0.2 mIU/L) observed in some cohorts. Thyroid volume remained largely unaffected in over 90% of the human studies reviewed, suggesting no widespread hypertrophic effects.