Adults with type 2 diabetes who use a GLP-1 receptor agonist for more than 1 year may have an increased risk for thyroid cancer, according to findings published in Diabetes Care.

“Our results suggest that thyroid cancer risk should be considered with GLP-1 receptor agonists, particularly in patients treated for 1 to 3 years,” Jean-Luc Faillie, MD, PhD, professor and head of the department of medical pharmacology and toxicology at Montpellier University Hospital and University of Montpellier in France, and colleagues wrote. “Complementary pharmacovigilance analysis with use of the worldwide adverse drug reactions database provided consistent results.”

Researchers conducted a case-control analysis of data from France’s national health care insurance system database. People with type 2 diabetes using GLP-1 receptor agonists, DPP-IV inhibitors or multiple therapies combining metformin, sulfonylureas, repaglinide, alpha-glucosidase inhibitors or thiazolidinediones from 2006 to 2018 were included. Researchers obtained incident cases of thyroid cancer from 2014 to 2018 through hospital diagnoses and medical procedures associated with thyroid cancer. People with thyroid cancer were matched with up to 20 control participants without thyroid cancer by age, sex and diabetes duration. A lag time of 6 months before cancer diagnosis was used to reduce the risk of reverse causation. Researchers identified adults who used GLP-1 receptor agonists and DPP-IV inhibitors and obtained the duration of use in the 6 years before the lag time.

The study included 3,746,672 people with type 2 diabetes, of whom 4,466 developed thyroid cancer. After excluding those with a history of cancer, researchers analyzed data from 2,562 adults with thyroid cancer and 45,184 matched controls without thyroid cancer.

Before the lag time, 12% of the thyroid cancer group and 9.6% of the control group used GLP-1 receptor agonists, with more than 80% in both groups using liraglutide (Victoza, Novo Nordisk). Those currently using a GLP-1 receptor agonist had a higher risk for thyroid cancer compared with those not currently using the medication (adjusted HR = 1.46; 95% CI, 1.23-1.74). Those who used a GLP-1 receptor agonist for 1 to 3 years (aHR = 1.58; 95% CI, 1.27-1.95) or more than 3 years (aHR = 1.36; 95% CI, 1.05-1.74) also had a higher risk for thyroid cancer than non-users.

Adults using DPP-IV inhibitors for more than 3 years had an increased risk for thyroid cancer compared with nonusers (aHR = 1.19; 95% CI, 1.04-1.35), but no other significant associations with the drug class were observed.

Researchers also conducted an analysis using data from the WHO’s pharmacovigilance database from April 28, 2005, to March 1, 2021. Data were collected to estimate associations between GLP-1 receptor agonist use and the risk of differential reporting of thyroid cancer compared with other diabetes drugs, excluding insulin. Associations were estimated using proportional reporting ratio.

In the analysis, 606 spontaneous reports of thyroid cancer with GLP-1 receptor agonist use were found. Disproportionate reporting of any thyroid cancer (proportional reporting ratio, 30.5; 95% CI, 25.1-37.2) and medullary thyroid cancer (proportional reporting ratio, 28.7; 95% CI, 16.1-51.1) were observed with GLP-1 receptor agonist use.

“Clinicians should be aware of this potential risk [for thyroid cancer] in initiating a GLP-1 receptor agonist and carefully monitor exposed patients, especially in the presence of other risk factors for thyroid cancer,” the researchers wrote.