GLP-1 Receptor Agonists and Thyroid Cancer: Differentiating Cancer Type

Currently, the FDA has approved 4 glucagon-like peptide 1 (GLP-1) receptor agonists: albiglutide, dulaglutide, exenatide and liraglutide. All GLP-1 receptor antagonists have been associated with thyroid cancer in rodents, and in fact carry a boxed warning about the potential for cancer in humans. This leads many clinicians to ask if they should be concerned about using these drugs in patients who have or develop specific types of thyroid cancer—this is a clinical dilemma since these drugs work well and discontinuing them creates risk of elevated glucose and the need to readjust treatment. A One Minute Consult in the March 2015 issue of Cleveland Clinic Journal of Medicine summarizes important facts succinctly:

• There are 4 types of thyroid cancer: medullary, papillary, follicular, and anaplastic.
• GLP-1 receptor agonists can be safely used in all patients with papillary and follicular thyroid cancers; these develop from the thyroid follicular epithelium.
• GLP-1 receptor agonists are currently contraindicated in patients with medullary thyroid cancer (which is very rare in humans) and in patients with multiple endocrine neoplasia 2 (MEN-2). The latter is not thyroid cancer.
• Exercise caution when using GLP-1 receptor agonists in patients with familial thyroid cancer or genetic predisposition to papillary or follicular thyroid cancer. These cancers express GLP-1 receptors.
• Several other human tumors have express GLP-1 receptors, but animal studies have not linked GLP-1 receptor agonists to these cancers.

The authors conclude GLP-1 receptor agonists’ benefits in type 2 diabetes mellitus outweigh risks of medullary thyroid cancer, and except in patients who have or are at risk for this rare cancer, clinicians can prescribe them without worry.