GLP-1RA initiation associated with new thyroid cancer diagnoses

GLP-1RA initiation associated with new thyroid cancer diagnoses

Short-term increase in thyroid cancer diagnoses observed with GLP-1RA initiation, likely due to increased case detection rather than new cancer development

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

Does GLP-1RA affect the risk of thyroid cancer?

GLP-1RAs are highly effective drugs for the treatment of T2D and obesity while conferring protection against cardiovascular disease, renal disease, and hepatic steatosis in these patients. Current estimates show that 27.1% of patients are currently using GLP-1RA, which is a three-fold increase since 2018, when approximately 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, given the widespread use of these drugs, it is important to elucidate the potential role of GLP-1RA use in the development of thyroid cancer.

About the study

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

The main aim of the analysis was to compare the effects of sodium-glucose cotransporter 2 inhibitors (SGLT2I), GLP-1RA, dipeptidyl peptidase 4 inhibitors (DPP4I) and sulfonylhure (SU) to determine the potential association between GLP-1RA and thyroid cancer.

Individuals 21 years of age or older were at moderate risk of cardiovascular disease and had a newly filled prescription for SGLT2I, GLP1RA, DPP4I, or SU between January 1, 2014 and December 31, 2021 for analysis. The date of the first prescription was referred to as the index date.

Patients with missing information or patients who provided conflicting information about sex, year of birth, or region were excluded from the analysis. Patients prescribed study medication within 1 year before the index date or 30 days after the index date were pregnant, receiving insulin, or also diagnosed with cancer.

Study results

The current study included 351,913 adult patients with a mean age of 65.3 years with almost 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 compared to the non-GLP-1RA medications prescribed. Among patients initiating GLP-1RA use in the first year of follow-up, thyroid cancer HR was significantly higher at 1.85 compared to patients initiating non-GLP-1RA medications. Thereafter, HR declined to 1.27 in thyroid cancer among GLP-1RA users with two or more years of treatment control.

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 in SU and SGLT2I users were 1.32 and 1.16, respectively. In piecewise models, patients who initiated GLP-1RA treatment had a HRD of 1.75 and 3.30 compared to SU and SGLT2I users.

Overall, the relative analysis reported a higher risk of thyroid cancer in patients prescribed GLP-1RA medications compared to patients prescribed other medications. GLP-1RA users were also significantly more likely to undergo thyroid ultrasound 12 months after starting treatment compared to non-GLP-1RA users.

No difference in appendicitis hospitalization rates was observed across all groups.

Conclusions

In the current study, a low absolute risk of thyroid cancer was observed in patients treated with GLP-1RA. Importantly, the observed increase in the relative risk of new thyroid cancer diagnoses was limited to the first year after GLP-1RA initiation.

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

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