Risk of Thyroid Tumors With GLP-1 Receptor Agonists: A Retrospective Cohort Study
Daniel R. Morales, Fan Bu, Benjamin Viernes, Scott L. DuVall, Michael E. Matheny, Katherine Simon, Thomas Falconer, Lauren R. Richter, Anna Ostropolets, Wallis C. Y. Lau, Kenneth K. C. Man, Shounak Chattopadhyay, Nestoras Mathioudakis, Evan Minty, Akihiko Nishimura, Feng Sun, Can Yin, Sarah Seager, Yi Chai, Jin Zhou, Yuan Lu, Carlen Reyes, Andrea Pistillo, Talita Duarte‐Salles, Clair Blacketer, Martijn J. Schuemie, Patrick Ryan, Harlan M. Krumholz, George Hripcsak, Rohan Khera, Marc A. Suchard
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 [0.87-1.23]; GLP-1RA vs. DPP-4i HR range from 0.78 [0.60-1.01] to 0.93 [0.83-1.04]). Analysis using thyroid malignancy and including a 1-year lag period produced similar conclusions. CONCLUSIONS: In patients with T2DM initiating second-line treatments, we observed no increased risk of thyroid tumors with GLP-1RA exposure.