SAT-614 - GLP-1 Receptor Agonists and Thyroid Cancer Risk in Type 2 Diabetes: A Systematic Review of Clinical Evidence

Background:
Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are widely used in type 2 diabetes mellitus (T2DM) for glycemic control, weight reduction, and cardiovascular benefit. Concerns regarding thyroid safety, particularly medullary thyroid carcinoma (MTC), persist based on preclinical data and current prescribing warnings.

Methods:
A systematic review was conducted per PRISMA 2020 guidelines. PubMed, Embase, Scopus, and Cochrane Library were searched (2018–2025) for studies evaluating thyroid cancer outcomes in adults with T2DM treated with GLP-1RAs. Of 1,442 records identified, 692 were screened after duplicate removal and 140 full texts reviewed; 9 studies met inclusion criteria, including randomized controlled trials and large multinational cohorts. Meta-analysis was not performed due to heterogeneity.

Results:
Across 9 studies with follow-up ranging from 1.8 to 8 years, GLP-1RA use was not associated with a statistically significant increase in thyroid cancer risk. Randomized trials demonstrated no increase in calcitonin levels, C-cell hyperplasia, or MTC incidence. Large population-based cohorts, including studies with >4 million participants, showed hazard ratios approximating unity across multiple active comparators, with no exposure–response relationship observed. Early increases in diagnoses in some studies likely reflect detection bias, and limited follow-up and low event rates restrict assessment of long-latency risk. Long-term propensity-matched data further demonstrated no association with thyroid cancer or MTC. A single study reported increased risk with short-term exposure, likely influenced by surveillance bias.

Conclusion:
GLP-1RA use is not associated with a statistically significant increase in thyroid cancer risk, including MTC, in adults with T2DM. Clinically, these findings support confident prescribing, indicating a low observed MTC risk in the general population, while reinforcing that established metabolic and cardiovascular benefits outweigh theoretical risk, with appropriate caution in patients with personal or family history of MTC or MEN2.

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