Do GLP-1 Medications Increase Thyroid Cancer Risk? A New Study Weighs In

Credit: Adobe Stock/Proxima Studio

A study of more than 350,000 patients and found that, overall, patients who were treated with glucagon-like peptide-1 receptor agonists (GLP-1 RAs) did not have a significantly higher risk of thyroid cancer. However, there was a noticeable increase in thyroid cancer diagnoses within the first year of starting GLP-1 RA treatment. Investigators suggest this may be due to earlier detection rather than an actual increase in the susceptibility to thyroid cancer.

GLP-1 RAs were prescribed to approximately 64 million patients in the U.S. between 2015 and 2020 — with a growth rate of approximately 10% to 30% per year. This is due in part to its proven efficacy in treating type 2 diabetes and obesity, conditions that affect 14.7% and 41.9% of Americans, respectively. However, there has been increasing concern regarding the possible link between GLP-1 RAs and thyroid cancer.

“GLP-1 RAs have been associated with the development of medullary thyroid cancer in rodents in a dose- and treatment duration-dependent manner,” wrote a team of investigators led by Juan P. Brito, M.D., an endocrinologist associated with Division of Endocrinology, Diabetes, Metabolism and Nutrition at Mayo Clinic. “As a result, the U.S. Food and Drug Administration (FDA) has warned against the use of GLP-1 RA by individuals with personal or family history of medullary thyroid cancer and hereditary conditions associated with this type of cancer.”

With this in mind, investigators evaluated whether people with type 2 diabetes who take GLP-1 RAs are at a higher risk of developing thyroid cancer compared with those taking other common diabetes medications. They identified a diverse patient population using data from medical and pharmacy claims individuals enrolled in commercial and Medicare Advantage plans.

Eligible patients were aged 21 years or older, had type 2 diabetes, were at moderate risk for cardiovascular disease and did not have a history of thyroid cancer. These patients had newly filled prescriptions for GLP-1 RAs, dipeptidyl peptidase-4 (DPP4) inhibitors, sodium-glucose cotransporter 2 (SGLT2) inhibitors or sulfonylurea between January 2014 and December 2021.

Among the 351,913 patients, the mean age was 65.3 years and approximately half (49.3%) were female. Thyroid cancer diagnoses were similar across treatment groups (GLP-1 RA: 0.17%; SGLT2: 0.17%; sulfonylurea: 0.20%; and DDP4: 0.23%), demonstrating GLP-1 RA use was not linked to an increased cancer risk.

However, the risk of developing thyroid cancer was 1.85 times higher within the first year after initiating GLP-1 RA treatment compared with the other three drugs. This risk dropped to 1.27 during years one to two, and 0.78 in subsequent years.

This spike may be because those receiving GLP-1 RAs also had a significantly higher likelihood of undergoing thyroid ultrasonography during the first six to 12 months post-initiation when compared with non-GLP-1 RA users (1.2% vs. 0.8%, respectively; and 2.1% vs. 1.5%, respectively).

Investigators noted the comprehensive evaluation of a large, diverse group of patients strengthened the study, as did the comparison between GLP-1 RAs and other diabetes treatments. However, relying on administrative data to identify outcomes and time exposures limited the analysis. Additionally, they only included patients with diabetes, although GLP-1 RAs are used to treat other conditions, such as obesity, and to reduce cardiovascular disease risk.

“These results should be interpreted in light of methodological limitations, the relatively short follow-up period (particularly in the as-treated analysis) and potential unmeasured confounders,” investigators wrote. “These findings highlight the need for further research to fully understand the nature of this association.”