GLP-1RA initiation linked to new thyroid cancer diagnoses

Short-term increase in thyroid cancer diagnoses observed with GLP-1RA initiation, likely driven by heightened case detection rather than new cancer development

Study: GLP-1RA Use and Thyroid Cancer Risk. Image Credit: peterschreiber.media / Shutterstock.com

A recent JAMA Otolaryngology-Head & Neck Surgery study investigates the risk of incident thyroid cancer among adults diagnosed with type 2 diabetes (T2D) and being treated with either glucagon-like peptide-1 receptor agonists (GLP-1RAs) or other glucose-lowering medications.

Does GLP-1RA use impact the risk of thyroid cancer?

GLP-1RAs are highly effective medications used to treat T2D and obesity while simultaneously conferring protection against cardiovascular disease, kidney disease, and hepatic steatosis in these patients. Current estimates indicate that 27.1% of patients are currently using GLP-1RAs, which is a three-fold rise since 2018, when about 9.2% of patients were prescribed these medications.

Several studies have reported an increased risk associated with GLP-1RA use and the development of medullary thyroid cancer in rodents. These findings have led the United States Food and Drug Administration (FDA) to issue a warning against the use of GLP-1RAs by individuals with a family or personal history of medullary thyroid cancer.

Despite emerging evidence, the association between GLP-1RA and thyroid cancer in humans remains unclear. Therefore, considering the widespread use of these medications, it is crucial to elucidate the potential role of GLP-1RA use in the development of thyroid cancer.

About the study

The researchers of the current study conducted a secondary analysis using linked administrative claims data from health plans. The study cohort was diverse in race and ethnicity, age, geographic regions, income levels, and health insurance plans.

The primary goal of the analysis was to compare the effects of sodium-glucose cotransporter-2 inhibitors (SGLT2i), GLP-1RAs, dipeptidyl peptidase-4 inhibitors (DPP4i), and sulfonylureas (SU) to determine the potential association between GLP-1RA and thyroid cancer.

Individuals who were 21 years of age or older, were at moderate risk for cardiovascular disease, and had a newly filled prescription for SGLT2i, GLP1RA, DPP4i, or SU between January 1, 2014, and December 31, 2021 were considered for the analysis. The date of the first prescription was referred to as the index date.

Patients with missing information or those who provided conflicting information on sex, year of birth, or region were excluded from the analysis. Patients who were prescribed any study drug within one year preceding the index date or 30 days after the index date, were pregnant, received insulin, or were diagnosed with any cancer were also excluded.

Study findings

The current study included 351,913 adult patients with an average age of 65.3 years, with nearly equal representation of male and female patients. The percentage of patients diagnosed with thyroid cancer was 0.23% in the DPP4i group, 0.17% in the GLP-1RA group, 0.17% in the SGLT2i group, and 0.20% in the SU group.

The hazard ratio (HR) of thyroid cancer in the GLP-1RA group was 1.24 as compared to those prescribed non-GLP-1RA medications. Among patients initiating GLP-1RA use during the initial year of follow-up, the HR for thyroid cancer was significantly higher at 1.85 as compared to patients initiating non-GLP-1RA medications. Thereafter, the HR for thyroid cancer in GLP-1RA users declined to 1.27 with two or more years of treatment exposure.

The HR for thyroid cancer in the GLP-1RA group was 1.12, compared to 1.12 for patients initiating DPP4i treatment. The HRs for thyroid cancer among SU and SGLT2i users were 1.32 and 1.16, respectively. In piecewise models, patients beginning GLP-1RA treatment had an HR of 1.75 and 3.30 compared to SU and SGLT2i users, respectively.

Overall, the relative analysis reported a greater risk of thyroid cancer in patients prescribed GLP-1RA medications as compared to those using other medications. GLP-1RA users were also significantly more likely to undergo thyroid ultrasonography 12 months after the initiation of treatment as compared to non-GLP-1RA users.

Across the groups, no difference in the rate of appendicitis hospitalizations was observed.

Conclusions

The current study observed a lower absolute risk of thyroid cancer among patients treated with GLP-1RAs. Importantly, the observed rise in the relative risk of new thyroid cancer diagnoses was limited to the first year after GLP-1RA initiation.

Nevertheless, notable limitations of the study include a relatively short follow-up period and the potential presence of confounding factors. The enhanced early detection of thyroid cancer may have also increased the prevalence rate of its diagnosis.