Risk of Thyroid Tumors With GLP-1 Receptor Agonists: A Retrospective Cohort Study

IF 14.8 1区医学 Q1 ENDOCRINOLOGY & METABOLISM

Diabetes Care Pub Date : 2025-06-04 DOI:10.2337/dc25-0154

Daniel R. Morales, Fan Bu, Benjamin Viernes, Scott L. DuVall, Michael E. Matheny, Katherine R. 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 L. Seager, Yi Chai, Jin J. Zhou, Yuan Lu, Carlen Reyes, Andrea Pistillo, Talita Duarte-Salles, Clair Blacketer, Martijn J. Schuemie, Patrick B. Ryan, Harlan M. Krumholz, George Hripcsak, Rohan Khera, Marc A. Suchard

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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.

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GLP-1受体激动剂治疗甲状腺肿瘤的风险：一项回顾性队列研究

目的探讨胰高血糖素样肽1受体激动剂（GLP-1RA）的使用与甲状腺肿瘤发生风险的关系。研究设计和方法回顾性、主动比较新用户队列研究使用国际行政索赔和电子健康记录数据库。参与者包括先前接受二甲双胍治疗的2型糖尿病（T2DM）患者，开始GLP-1RA与新使用钠-葡萄糖共转运蛋白2抑制剂（SGLT2is），二肽基肽酶4抑制剂（DPP-4is）和磺脲类药物（SUs）的患者。结果为甲状腺肿瘤和甲状腺恶性。倾向评分匹配和分层用于调整混杂因素的意向治疗和治疗策略。采用Cox回归估计随机效应荟萃分析汇总的风险比（hr）。使用阴性结果评估未测量的混杂，并校准HR。结果共纳入GLP-1RAs患者460,032人，SGLT2is患者717,792人，DPP-4is患者2,0055,583人，SUs患者1,119,868人。只有美国的队列通过了研究诊断。在GLP-1RA队列中，甲状腺肿瘤发病率为每1000人年0.88 - 1.03。与SGLT2is、DPP-4is或SUs相比，GLP-1RA暴露与甲状腺肿瘤风险增加无关(荟萃分析：GLP-1RA与SGLT2i的危险度范围为0.83 [95% CI 0.57-1.27]至0.95 [0.85-1.06]；GLP-1RA与SU的HR范围为0.95[0.75-1.20]至1.03 [0.87-1.23]；GLP-1RA与DPP-4i的HR范围为0.78[0.60-1.01]至0.93[0.83-1.04])。对甲状腺恶性肿瘤的分析，包括1年的滞后期，得出了类似的结论。结论：在接受二线治疗的T2DM患者中，我们观察到GLP-1RA暴露没有增加甲状腺肿瘤的风险。

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来源期刊

Diabetes Care 医学-内分泌学与代谢

CiteScore

27.80

自引率

4.90%

发文量

449

审稿时长

1 months

期刊介绍： The journal's overarching mission can be captured by the simple word "Care," reflecting its commitment to enhancing patient well-being. Diabetes Care aims to support better patient care by addressing the comprehensive needs of healthcare professionals dedicated to managing diabetes. Diabetes Care serves as a valuable resource for healthcare practitioners, aiming to advance knowledge, foster research, and improve diabetes management. The journal publishes original research across various categories, including Clinical Care, Education, Nutrition, Psychosocial Research, Epidemiology, Health Services Research, Emerging Treatments and Technologies, Pathophysiology, Complications, and Cardiovascular and Metabolic Risk. Additionally, Diabetes Care features ADA statements, consensus reports, review articles, letters to the editor, and health/medical news, appealing to a diverse audience of physicians, researchers, psychologists, educators, and other healthcare professionals.