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.