In 2022 and 2023, prescriptions for glucagon-like peptide 1 receptor agonist (GLP-1 RA or GLP-1) medications increased significantly, even resulting in shortages of the medications.1 GLP-1 medications, like semaglutide, liraglutide, and dulaglutide, have been approved in the U.S. as a treatment for type 2 diabetes for several years, but they only recently made their way into national media headlines, largely due to their recent approval and use for weight loss. Initial animal studies and studies of other GLP-1 medications have shown an increased risk of thyroid cancer, which has prompted a warning of the potential side effect to patients prescribed GLP-1 medications.2,3 We sought to understand whether patients prescribed these medications were at an increased risk of thyroid cancer in the five years after their initial diabetes diagnosis compared to patients prescribed insulin, another frequently prescribed medication for the treatment of type 2 diabetes.
We compared 24,221 type 2 diabetic patients prescribed semaglutide, 49,266 patients prescribed liraglutide, and 45,153 patients prescribed dulaglutide to 551,119 type 2 diabetic patients prescribed insulin to determine whether there were differences in the risk of thyroid cancer in each group. We found that the rate of thyroid cancer in the five years after diabetes diagnosis was lower for patients prescribed dulaglutide or semaglutide than patients prescribed insulin, as shown in Figure 1. The observed rate of thyroid cancer in patients prescribed liraglutide is similar to that of patients prescribed insulin. A sensitivity analysis adjusted for timing of treatment and HbA1c showed that there was no increased risk of thyroid cancer for any of the three GLP-1 medications studied as compared to insulin.
Previous studies have shown people with a BMI ≥ 40, also known as class 3 obesity, and women have an increased risk of thyroid cancer.4,5 We stratified the rates of thyroid cancer by patient BMI to understand how BMI might interplay with the diabetic medication prescribed. For this analysis, we compared patients prescribed insulin to patients prescribed any GLP-1 medication. We found that the rate of thyroid cancer was lower in the patients prescribed GLP-1 medications, but the decrease was only statistically significant in the patients with a BMI between 30 and 35, or class 1 obesity, as shown in Figure 2.
Our results aligned with previous studies showing rates of thyroid cancer for females are around double the rates for males for both insulin and GLP-1 RA patients, as shown in Figure 3.
These data come from Cosmos, a HIPAA-defined Limited Data Set of more than 214 million patients from 218 Epic organizations including 1,235 hospitals and more than 26,800 clinics, serving patients in all 50 states and Lebanon. This study was completed by two teams that worked independently, each composed of a clinician and research scientists. The two teams came to similar conclusions. Graphics by Brian Olson.
- Putka S. Diabetes patients also struggle to access GLP-1 agonists: patients are making substitutions, crossing state lines, stopping care because of shortages. Med Page Today. Diabetes Patients Also Struggle to Access GLP-1 Agonists | MedPage Today. Accessed September 19, 2023.
- National Library of Medicine. Semaglutide Injection. MedlinePlus. Semaglutide Injection: MedlinePlus Drug Information. Accessed July 25, 2023.
- Benzin J, Gouverneur A, Mathieu C, et al. GLP-1 Receptor Agonists and the Risk of Thyroid Cancer. Diabetes Care. 1 February 2023; 46 (2): 384–390. https://doi.org/10.2337/dc22-1148
- Lauby-Secretan B, Scoccianti C, Loomis D, et al. Body Fatness and Cancer–Viewpoint of the IARC Working Group. N Engl J Med. 2016;375(8):794–798. doi:10.1056/NEJMsr1606602.
- American Cancer Society. Thyroid Cancer Risk Factors. Thyroid Cancer Risk Factors | Risk Factors for Thyroid Cancer | American Cancer Society. Accessed on August 11, 2023.
