Investigating the association between incretin-based therapies and thyroid cancer incidence among US Medicare beneficiaries with diabetes.

[INTRODUCTION] Preclinical studies suggest a potential link between glucagon-like peptide 1 receptor agonists (GLP-1RA) and thyroid cancer (TC), yet it is unclear if this risk translates to humans.

[RESEARCH DESIGN AND METHODS] We estimated the comparative effect of incretin-based therapies (GLP-1RA and dipeptidyl-peptidase-4 inhibitors (DPP-4i)) versus sodium-glucose cotransporter-2 inhibitors (SGLT-2i) on TC incidence among US older adults with type 2 diabetes. We defined TC as a thyroidectomy followed by ≥2 separate diagnoses codes for malignant neoplasm of thyroid gland within 90 days. We estimated adjusted 3-year cumulative risk differences of TC (aRDs) with 95% CIs using weighted Kaplan-Meier survival functions, and adjusted HRs using weighted Cox models.

[RESULTS] We included 73 388 new users in the GLP-1RA versus SGLT-2i cohort (mean age 72.4 years, men: 48.3%) and 106 274 in the DPP-4i versus SGLT-2i cohort (mean age 74.6 years, men: 44.9%). At 3 years and a median duration of treatment of 0.82-1.15 years, the aRD for GLP-1RA versus SGLT-2i for TC was -23 per 10 000 (95% CI: -51 to 4) and the aRD for DPP-4i versus SGLT-2i was -2 per 10 000 (95% CI: -17 to 13). Secondary and sensitivity analyses were consistent.

[CONCLUSIONS] Our study of US Medicare beneficiaries with type 2 diabetes suggests that the initiation of incretin-based therapies may not increase the 3-year risk of TC compared with initiation of SGLT-2i. This finding offers reassurance for short-term use but does not eliminate the possibility of increased long-term or subtype-specific risks.