Glucagon-Like Peptide 1 Receptor Agonists and Risk of Thyroid Cancer: An International Multisite Cohort Study

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Glucagon-Like Peptide 1 Receptor Agonists and Risk of Thyroid Cancer: An International Multisite Cohort Study

Introduction: Concerns have been raised that glucagon-like peptide 1 receptor agonists (GLP1-RAs) may increase the risk of thyroid cancer, but evidence remains conflicting. We therefore investigated if GLP1-RA use, compared with use of dipeptidyl peptidase-4 inhibitors (DPP-4is), was associated with thyroid cancer risk in patients with type 2 diabetes.

Methods: This multisite cohort study with subsequent meta-analysis included six population-based databases from Canada (Ontario), Denmark, Norway, South Korea, Sweden, and Taiwan. Study populations comprised patients with type 2 diabetes between 2007 and 2023. Cox regression models estimated hazard ratios (HR) and 95% confidence intervals (CIs) for thyroid cancer among GLP1-RA users compared with DPP-4is. Models were weighted using standardized mortality ratio weights generated from time-specific propensity scores. Site-specific HRs were pooled using a fixed-effects model.

Results: We identified 98,147 users of GLP1-RA and 2,488,303 users of DPP-4i, with the median follow-up among users of GLP1-RA ranging from 1.8 to 3.0 years. Overall, use of GLP1-RA relative to use of DPP-4i was not associated with an increased risk of thyroid cancer (pooled weighted HR 0.81, CI 0.59-1.12). Similarly, we observed no increased risk in thyroid cancer with increasing cumulative dose of GLP1-RA among GLP1-RA ever-users. Subgroup analysis of types of thyroid cancer was not possible. Results remained consistent across a range of supplementary analyses. Discussion: In this large multisite study, utilizing data from six population-based databases, we found no evidence that GLP1-RA use is associated with an increased risk of thyroid cancer with follow-up ranging from 1.8 to 3.0 years, providing some reassurance to patients and clinicians about the short-term safety of these drugs. Nevertheless, evidence was insufficient to rule out excess risk with long-term use, due to the short f ollow-up. Copyright 2025, Mary Ann Liebert, Inc., publishers.

Authors : Baxter S.M.; Lund L.C.; Andersen J.H.; Brix T.H.; Hegedüs L.; Hsieh M.H.; Su C.T.; Cheng M.C.; Chang Z.C.; Lai E.C.; Hussain S.; Chu C.; Gomes T.; Antoniou T.; Eskander A.; Bouck Z.; Tadrous M.; Bea S.; Choi E.-Y.; Shin J.-Y.; Modig K.; Talbäck M.; Ljung R.; Gulseth H.L.; Karlstad I.; Hicks B.; Pottegård A.

Source : Mary Ann Liebert Inc.