BACKGROUND
The weight loss medications known as glucagon-like peptide-1 receptor agonists (GLP-1RAs) have emerged as effective therapies for both obesity and diabetes since their approval by the US Food and Drug Administration (FDA) in 2005. However, the FDA has warned against using these medications in patients with a personal or family history of medullary thyroid carcinoma (MTC). This is because animal studies with these drugs showed that GLP-1RAs could increase the growth of the parafollicular C cells, which can develop into MTC, in mice. To date, despite human studies that not shown an increase in MTC cases among patients treated with GLP-1RA drugs, these drugs continue to have the Black Box warning about a possible association with MTC.

MTC is a rare thyroid cancer (<5% of thyroid cancer cases) that may run in families. The most common type of thyroid cancer is papillary thyroid cancer, which arises from the thyroid follicular cells. Thyroid follicular cells also contain GLP-1 receptors, raising the question of whether GLP-1RA exposure could increase the growth of papillary thyroid cancers. This is especially important since small papillary thyroid cancer can be watched by serial ultrasounds rather than removed by surgery, known as active surveillance. The aim of this study was to evaluate the impact of GLP-1RA exposure on cancer growth and progression in patients with low-risk papillary thyroid cancer undergoing active surveillance.

THE FULL ARTICLE TITLE
Patrizio A, et al. Effect of GLP-1 receptor agonists on patients with thyroid carcinomas undergoing active surveillance. J Endocr Soc.2025;10(1):bvaf182; doi: 10.1210/ jendso/bvaf182. PMID: 41376649.

SUMMARY OF THE STUDY
This study evaluated 18 patients on GLP-1RA therapy selected from the 441 patients with low-risk papillary thyroid cancer undergoing active surveillance at Memorial Sloan Kettering Cancer Center (MSKCC). According to the MSKCC protocol, the maximum cancer diameter of the papillary thyroid cancer in the study patients was ≤1.5 cm without evidence of extension of the cancer beyond the thyroid or spread to the lymph nodes in the neck.

Additional inclusion criteria for this study were follow-up at MSKCC for ≥6 months with neck ultrasounds performed every 6 months for the first 2 years, yearly for the next 3 years, and then approximately every 2 years for ongoing follow-up, and GLP-1RA exposure for ≥6 months.

The 18 study patients who were exposed to GLP-1RA therapy and that had 19 low-risk papillary thyroid cancers were matched with 37 patients with 38 cancers with similar cancer size undergoing active surveillance at MSKCC who were never exposed to this group of medications. Cancer size changes and cancer volumes were then compared between the two groups. Significant cancer growth was defined as an increase of ≥3 mm in any diameter and/or >72% increase in the cancer volume during the study. Patients were followed for an average of 5.5 years, with an average GLP-1RA exposure of 25 months.

Most cancers in both groups remained stable over time, with a small percentage showing significant growth or shrinkage. There was no statistically significant difference in cancer growth between patients treated with a GLP-1RA and those who were not. In addition, starting or stopping the GLP-1RA did not change the rate at which the cancers were growing. Interestingly, a longer exposure to GLP-1RA was associated with a greater decrease in cancer volume during the study. No patients developed spread of the cancer outside of the thyroid or the neck, and none underwent surgery during the study period.

WHAT ARE THE IMPLICATIONS OF THIS STUDY?
Overall, the study suggests that GLP-1RA therapy does not induce cancer growth and does not affect the cancer progression in patients with low-risk papillary thyroid cancer. This study confirms that GLP-1RA therapy appears to be in safe in patients with papillary thyroid cancer. While larger studies are needed to confirm these findings, this study should be reassuring to patients with papillary thyroid cancer.

— Alina Gavrila, MD, MMSc and Elie Naous, MD

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