Risk of thyroid tumors with GLP-1 receptor agonists: a retrospective cohort study

Objective: To assess the association between glucagon-like peptide-1 receptor agonists (GLP-1RA) use and risk of incident thyroid tumors.

Research Design and Methods: Retrospective new user active comparator cohort study using international administrative claims and electronic health record databases. Participants included T2DM patients with prior metformin therapy initiating GLP-1RA versus new users of sodium-glucose transport protein 2 inhibitors (SGLT2I), dipeptidyl peptidase IV inhibitors (DPP4I) and sulfonylureas (SU). The outcome was incident thyroid tumor and thyroid malignancy. Propensity score (PS) matching, and stratification were used for confounding adjustment with intention-to-treat and on-treatment strategy. Cox regression was used to estimate hazard ratios (HR) pooled using random-effects meta-analysis. Unmeasured confounding was evaluated using negative outcomes, with calibration of the HR.

Results: 460,032 users of GLP-1RA, 717,792 users of SGLT2I, 2,055,583 users of DPP4I and 1,119,868 users of SU were included. Only US cohorts passed study diagnostics. Thyroid tumor incidence ranged from 0.88 to 1.03 per 1000 person years in GLP-1RA cohorts. GLP-1RA exposure was not associated with an increased risk of thyroid tumors compared with SGLT2I, DPP4Is or SUs (Meta-analysis: GLP-1RA vs SGLT2I range HR 0.83 (0.57-1.27) to HR 0.95 (0.85–1.06); GLP-1RA vs SU range HR 0.95 (0.75-1.20) to HR 1.03 (0.87-1.23); GLP-1RA vs DPP4I range HR 0.78 (0.60-1.01) to HR 0.93 (0.83-1.04)). Analysis using thyroid malignancy, and including a 1-year lag period produced similar conclusions.

Conclusion: In T2DM patients initiating second-line treatments, we observed no increased risk of thyroid tumors with GLP-1RA exposure