BACKGROUND
GLP1 is a hormone naturally made in the body that helps to control blood sugar. GLP1 receptor agonists (GLP1-RAs) are medications that act like GLP1 and are used to treat diabetes and obesity. These medications lower blood sugar and help people lose weight, protect the heart and the kidneys, and may even benefit the brain, making them increasingly popular among patients and doctors. As more and more people use GLP1-RAs, concerns about a possible link to thyroid cancer were raised. GLP1 receptors were found in thyroid cancer cells, suggesting these medications could potentially affect them. In animal studies with GLP1-RAs, an increase in C-cell tumors was seen, which are associated with medullary thyroid cancer, which is a rare form of thyroid cancer. However, it’s unclear if this risk applies to humans. Studies in humans showed mixed results, some found increased risk for thyroid cancer and some did not.

Given the increasing number of people using these medications and the conflicting study results, the researchers designed a large, international study to clarify whether GLP1-RAs increase the risk of thyroid cancer and whether higher doses overtime make the risk bigger.

THE FULL ARTICLE TITLE
Baxter SM, et al. Glucagon-like peptide 1 receptor agonists and risk of thyroid cancer: an international multisite cohort study. Thyroid 2024; in press.

SUMMARY OF THE STUDY
Researchers studied medical records from 2007 to 2023 of people with type 2 diabetes from six countries: Canada, Denmark, Norway, South Korea, Sweden, and Taiwan. They compared 92,497 people who took GLP1-RAs with 2,484,408 people who took DPP-4 inhibitors. DPP4 inhibitors are also commonly used diabetes medications that help the body keep more of its natural GLP1 hormone. This makes them a good comparison to GLP1-RAs since both drugs treat the blood sugar similarly but work differently.

They followed these patients for up to 10 years to see if there was a difference in thyroid cancer cases. They used statistical methods to account for factors like age and other conditions to make sure the results were fair and accurate. However, they could not account for obesity because there was not enough data, even though obesity is a known risk factor for cancer, including thyroid cancer.

The results show that GLP1-RAs did not increase the risk of thyroid cancer compared to DPP-4 inhibitors. Taking higher doses of GLP1-RAs also did not raise the risk. The results were the same in all six countries, which means the findings were strong and trustworthy. The study could not assess the risk specifically for medullary thyroid cancer because there were too few cases.

WHAT ARE THE IMPLICATIONS OF THIS STUDY?
This large international study shows that the popular diabetes and weight loss drugs known as GLP1-RAs do not increase the risk of thyroid cancer in people with type 2 diabetes compared to DPP-4 inhibitors over up to 10 years. The findings are reassuring and confirm short-term safety, but more research is needed to understand any long-term risks, especially for medullary thyroid cancer. This is one of the largest studies on GLP1-RAs and thyroid cancer. The inclusion of many people from different countries makes the findings more reliable and relevant to more people. Patients were followed longer than in most previous research and were compared to a similar medication. These stronger methods make the results more trustworthy and give better answers about the safety of these medications. Patients and doctors can feel more confident using GLP1-RAs, especially given their benefits on blood sugar, weight and heart protection, while longer term effects continue to be studied.

— Ebru Sulanc, MD

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