Risk of thyroid cancer associated with glucagon‐like peptide‐1 receptor agonists and dipeptidyl peptidase‐4 inhibitors in patients with type 2 diabetes: A population‐based cohort study

Sep 22, 2023Diabetes, obesity & metabolism

Risk of Thyroid Cancer Linked to Two Diabetes Treatments in People with Type 2 Diabetes

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Abstract

The use of GLP-1 receptor agonists (GLP-1RAs) and DPP-4 inhibitors is not associated with an increased risk of thyroid cancer in individuals with type 2 diabetes.

GLP-1RAs had a weighted hazard ratio of 0.98 for thyroid cancer risk compared to SGLT2 inhibitors.
DPP-4 inhibitors showed a hazard ratio of 0.95 for thyroid cancer risk when compared to SGLT2 inhibitors.
No significant differences were found in subgroup analyses regarding thyroid cancer risk.
Sensitivity analyses, including different definitions of thyroid cancer, supported the primary findings.

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AIMS: To determine the potential association between the use of either glucagon-like peptide-1 receptor agonists (GLP-1RAs) or dipeptidyl peptidase-4 (DPP-4) inhibitors, and the risk of thyroid cancer in individuals with type 2 diabetes.

MATERIALS AND METHODS: This population-based cohort study used claims data from the Korean National Health Insurance Database, 2014-2020. Two distinct cohorts were established to compare each incretin-based drug with sodium-glucose cotransporter-2 (SGLT2) inhibitors, chosen as active comparators because of their previous non-association with thyroid cancer, and their common usage as add-on therapy to metformin along with GLP-1RAs and DPP-4 inhibitors. The first cohort included 21 722 new users of GLP-1RAs and 326 993 new users of SGLT2 inhibitors, whereas the second cohort included 904 300 DPP-4 inhibitor new users and 112 017 SGLT2 inhibitor new users. The outcome was the time to incident thyroid cancer. Weighted Cox proportional models were used to estimate hazard ratios of thyroid cancer incidence associated with incretin-based drugs of interest.

RESULTS: The use of GLP-1RAs was not associated with an increased risk of thyroid cancer (weighted hazard ratio 0.98, 95% confidence interval 0.62-1.53) compared with that of SGLT2 inhibitors. Using DPP-4 inhibitors was also not associated with an increased risk of thyroid cancer (0.95, 0.79-1.14) compared with that of SGLT2 inhibitors. No significant effect modifications were observed across subgroup analyses. Sensitivity analyses, including alternative outcome definition analysis of medullary thyroid cancer, were consistent with the primary analysis results.

CONCLUSIONS: GLP-1RAs and DPP-4 inhibitors were not associated with an increased risk of thyroid cancer in individuals with type 2 diabetes.

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Risk of thyroid cancer associated with glucagon‐like peptide‐1 receptor agonists and dipeptidyl peptidase‐4 inhibitors in patients with type 2 diabetes: A population‐based cohort study

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