GLP-1 receptor agonists associated with thyroid cancer

Patients taking a glucagon-like peptide-1 (GLP-1) receptor agonist had about one and a half times the risk of developing thyroid cancer compared to similar controls, according to an observational French study.

There was an increased risk of all thyroid cancer and medullary thyroid cancer after one to three years of use of a glucagon-like peptide-1 (GLP-1) receptor agonist, a French study of an insurance database found.

To determine whether GLP-1 receptor agonists were associated with increased risk of thyroid cancer, researchers conducted a nested case-control analysis of patients treated from 2006 to 2018 in the French national health care insurance system database. Exposure to GLP-1 receptor agonists was measured within the six years preceding a six-month lag-time period. Patients were matched with up to 20 controls on age, sex, and length of diabetes. Results were published Nov. 10 by Diabetes Care.

Overall, 3,746,672 patients with type 2 diabetes were identified, from which 2,562 case-patients with thyroid cancers were matched with 45,184 controls. Increased risk for all thyroid cancer was associated with current use of a GLP-1 receptor agonist (hazard ratio [HR], 1.46; 95% CI, 1.23 to 1.74) and cumulative use for one to three years (HR, 1.58; 95% CI, 1.27 to 1.95) and more than three years (HR, 1.36; 95% CI, 1.05 to 1.74). Medullary thyroid cancer was also associated with GLP-1 receptor agonists (HR, 1.78; 95% CI, 1.04 to 3.05 for one to three years of use). The association between thyroid cancer and dipeptidyl peptidase-4 (DPP-4) inhibitors was close to significance but weak (HR, 1.10; 95% CI, 0.99 to 1.22) and significant but weak for cumulative use over three years (HR, 1.19; 95% CI, 1.04 to 1.35).

The study authors noted that GLP-1 receptors are present in human thyroid tissue or neoplastic thyroid C cells, suggesting a direct role of GLP-1 receptor activation in thyroid cancer development. Since DPP-4 inhibitors were also associated with higher risk for thyroid cancer at lower risk estimates, the authors stated it is possible that inhibition of DPP-4 results in increased endogenous GLP-1 levels but provides less GLP-1 receptor activation. Induced thyroid cancers could develop after a relatively short period of GLP-1 receptor agonist exposure, or GLP-1 receptor agonists could promote thyroid precancerous lesions, the authors observed.

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