Risk of Thyroid Tumors With GLP-1 Receptor Agonists: A Retrospective Cohort Study
Abstract
OBJECTIVE To assess the association between glucagon-like peptide 1 receptor agonist (GLP-1RA) use and risk of incident thyroid tumors. RESEARCH DESIGN AND METHODS The retrospective, active-comparator new-user cohort study used international administrative claims and electronic health record databases. Participants included patients with type 2 diabetes mellitus (T2DM) with prior metformin therapy initiating a GLP-1RA versus new users of sodium–glucose cotransporter 2 inhibitors (SGLT2is), dipeptidyl peptidase 4 inhibitors (DPP-4is), and sulfonylureas (SUs). The outcome was incident thyroid tumor and thyroid malignancy. Propensity score matching and stratification were used to adjust for confounders with an intention-to-treat and on-treatment strategy. Cox regression was used to estimate hazard ratios (HRs) pooled using a random-effects meta-analysis. Unmeasured confounding was evaluated using negative outcomes, with calibration of the HR. RESULTS A total of 460,032 users of GLP-1RAs, 717,792 users of SGLT2is, 2,055,583 users of DPP-4is, and 1,119,868 users of SUs were included. Only U.S. cohorts passed study diagnostics. Thyroid tumor incidence ranged from 0.88 to 1.03 per 1,000 person-years in GLP-1RA cohorts. GLP-1RA exposure was not associated with an increased risk of thyroid tumors compared with SGLT2is, DPP-4is, or SUs (meta-analysis: GLP-1RA vs. SGLT2i HR range from 0.83 [95% CI 0.57–1.27] to 0.95 [0.85–1.06]; GLP-1RA vs. SU HR range from 0.95 [0.75–1.20] to 1.03…
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Evidence Hub reads this as a cohort study, done in people. Its evidence level is 3 of 5 (Moderate · trial / cohort / secondary analysis). Trials without a large randomized design, cohorts and secondary analyses give moderate evidence.
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