Glucagon-like peptide 1 (GLP-1) receptor agonist use does not significantly increase the risk of thyroid cancer, according to new research published in BMJ.1 However, the authors noted that the study results cannot exclude a small increase in risk.
GLP-1s, which are approved to treat type 2 diabetes and weight loss, have experienced a rapid increase in use recently. For example, semaglutide (Ozempic) users increased from 569 in 2019 to 22891 in 2022.2 Although previous research has found that GLP-1s increased rates of thyroid C cell tumors in rodents, whether these findings are relevant to humans remains unknown.
Key Takeaways
- New research in BMJ suggests that the use of glucagon-like peptide 1 (GLP-1) receptor agonists, prescribed for type 2 diabetes and weight loss, is not significantly linked to an increased risk of thyroid cancer.
- A cohort study conducted by researchers from the Karolinska Institutet examined data from over 437,000 adult patients across Denmark, Norway, and Sweden. Comparing GLP-1 users to those on dipeptidyl peptidase 4 (DPP4) inhibitors, the study found no substantial difference in thyroid cancer incidence rates.
- While the study provides reassurance regarding the safety of GLP-1 analogues in relation to thyroid cancer, limitations such as the need for longer follow-up periods and the inability to assess certain patient subgroups suggest further research is warranted.
“We know from randomized clinical trials that [GLP-1s] have positive effects, but clinical reality is different with patients varying in disease severity, comorbidities, and adherence to treatment recommendations,” Björn Pasternak, principal researcher on the study, said in a release.3 “It’s therefore essential to investigate how these medicines perform in everyday clinical settings.”
A team of investigators from the Karolinska Institutet in Sweden conducted a cohort study to examine if GLP-1 use is associated with an increased risk of thyroid cancer. Data from 2007 to 2021 was gathered from health care registers in Denmark, Norway, and Sweden. The registers included population, prescription drug, national patient, and cancer data.
The study cohort included 437077 adult patients between 18 to 84 years of age who were new users of either a GLP-1 or a dipeptidyl peptidase 4 (DPP4) inhibitor. Patient exclusion criteria included a history of thyroid or any other cancer in the previous year, end stage illness, human immunodeficiency virus (HIV) infection, or major pancreatic disease. Patients on GLP-1s were compared to patients on DPP4s and were followed for a mean follow-up time of 3.9 years and 5.4 years, respectively.
READ MORE: Ozempic, Other GLP-1 Therapies Caused Major Increase in Medicare Spending
Out of 145410 patients treated with a GLP-1, investigators found that 76 went on to develop thyroid cancer during the follow-up period. In patients treated with a DPP4, 184 of 291667 developed thyroid cancer. This resulted in incidence rates of 1.33 and 1.46 per 10000 patients, respectively, with a hazard ratio of 0.93. The most common type of thyroid cancer was papillary, followed by follicular, and medullary.
In an additional analysis that compared 111744 patients treated with GLP-1s to 148179 patients treated with sodium-glucose cotransporter 2 (SGLT2) inhibitors, GLP-1 use was not associated with an increased risk of thyroid cancer compared to SGLT2 use.
“We cannot rule out that the risk of certain subtypes of thyroid cancer is increased in smaller patient groups that we could not study here, for example in people with a high congenital risk of medullary thyroid cancer who are advised against using these drugs,” Peter Ueda, assistant professor at the Department of Medicine, Solna, at Karolinska Institutet, said in a release.3
Study limitations include the possible need for further follow-up due to cancer latency, a lack of data on other GLP-1s, the observational design of the study, the possibility of confounding and time related biases, a lack of data on family history, ionizing radiation, iodine intake and height, and an inability to assess smaller subgroups of patients.
“Many people take these medicines, so it is important to study potential risks associated with them,” Pasternak said in a release.3 “Our study covers a broad group of patients and provides strong support that GLP-1 analogues are not associated with an increased risk of thyroid cancer.”
READ MORE: Diabetes Resource Center
References
1. Pasternak B, Wintzell V, Hviid A, et al. Glucagon-like peptide 1 receptor agonist use and risk of thyroid cancer: Scandinavian cohort study BMJ 2024; 385 :e078225 doi:10.1136/bmj-2023-078225
2. Watanabe JH, Kwon J, Nan B, et al. Trends in glucagon-like peptide 1 receptor agonist use, 2014 to 2022. J Am Pharm Assoc (2003). 2024;64(1):133-138. doi:10.1016/j.japh.2023.10.002
3. Popular diabetes drugs do not increase thyroid cancer risk, study suggests. News Release. Karolinska Institutet. April 10, 2024. Accessed April 16, 2024. https://news.ki.se/popular-diabetes-drugs-do-not-increase-thyroid-cancer-risk-study-suggests
