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

Daniel R Morales¹, Fan Bu², Benjamin Viernes^{3

4}, Scott L DuVall^{3

4}, Michael E Matheny^{5

6}, Katherine R Simon^{5

6}, Thomas Falconer⁷, Lauren R Richter^{7

8}, Anna Ostropolets⁷, Wallis C Y Lau^{9

10

11

12}, Kenneth K C Man^{9

10

11

12}, Shounak Chattopadhyay¹³, Nestoras Mathioudakis¹⁴, Evan Minty¹⁵, Akihiko Nishimura¹⁶, Feng Sun¹⁷, Can Yin¹⁸, Sarah L Seager¹⁸, Yi Chai⁹, Jin J Zhou^{13

19}, Yuan Lu²⁰, Carlen Reyes²¹, Andrea Pistillo²¹, Talita Duarte-Salles²¹, Clair Blacketer²², Martijn J Schuemie^{13

23}, Patrick B Ryan^{7

23}, Harlan M Krumholz^{20

24

25}, George Hripcsak⁷, Rohan Khera^{20

24

26}, Marc A Suchard^{3

13

27

28}

Affiliations

¹ Division of Population Health and Genomics, School of Medicine, University of Dundee, Dundee, U.K.
² Department of Biostatistics, University of Michigan at Ann Arbor, Ann Arbor, MI.
³ Veterans Affairs Informatics and Computing Infrastructure Department of Veterans Affairs, Salt Lake City, UT.
⁴ Department of Medicine, University of Utah School of Medicine, Salt Lake City, UT.
⁵ Tennessee Valley Healthcare System, Veterans Affairs Medical Center, Nashville, TN.
⁶ Department of Biomedical Informatics, Vanderbilt University Medical Center, Nashville, TN.
⁷ Department of Biomedical Informatics, Columbia University Irving Medical Center, New York, NY.
⁸ Division of Pediatric Endocrinology, Diabetes, and Metabolism, Department of Pediatrics, Columbia University Irving Medical Center, New York, NY.
⁹ Centre for Safe Medication Practice and Research, Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
¹⁰ Laboratory of Data Discovery for Health (D24H), Hong Kong Science Park, Hong Kong, China.
¹¹ Research Department of Practice and Policy, School of Pharmacy, University College London, London, U.K.
¹² Centre for Medicines Optimisation Research and Education, University College London Hospitals NHS Foundation Trust, London, U.K.
¹³ Department of Biostatistics, Fielding School of Public Health, University of California, Los Angeles, CA.
¹⁴ Division of Endocrinology, Diabetes, and Metabolism, Johns Hopkins University School of Medicine, Baltimore, MD.
¹⁵ Faculty of Medicine, O'Brien Institute for Public Health, University of Calgary, Calgary, Alberta, Canada.
¹⁶ Department of Biostatistics, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD.
¹⁷ Department of Epidemiology and Biostatistics, Peking University, Beijing, China.
¹⁸ DTA&AI, Real World Solutions, IQVIA, Durham, NC.
¹⁹ Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA.
²⁰ Section of Cardiovascular Medicine, Department of Internal Medicine, Yale University, New Haven, CT.
²¹ Real-World Epidemiology Research Group, Fundaci Institut Universitari per a la recerca a l'Atenci Primria de Salut Jordi Gol i Gurina, Barcelona, Spain.
²² Observational Health Data Analytics, Janssen Research and Development, LLC, Titusville, NJ.
²³ Epidemiology, Office of the Chief Medical Officer, Johnson & Johnson, Titusville, NJ.
²⁴ Center for Outcomes Research and Evaluation, Yale New Haven Hospital, New Haven, CT.
²⁵ Department of Health Policy and Management, Yale School of Public Health, New Haven, CT.
²⁶ Section of Health Informatics, Department of Biostatistics, Yale School of Public Health, New Haven, CT.
²⁷ Department of Biomathematics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA.
²⁸ Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA.

PMID: 40465422
PMCID: PMC12281980
DOI: 10.2337/dc25-0154

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

Daniel R Morales et al. Diabetes Care. 2025.

. 2025 Aug 1;48(8):1386-1394.

doi: 10.2337/dc25-0154.

Authors

Affiliations

¹ Division of Population Health and Genomics, School of Medicine, University of Dundee, Dundee, U.K.
² Department of Biostatistics, University of Michigan at Ann Arbor, Ann Arbor, MI.
³ Veterans Affairs Informatics and Computing Infrastructure Department of Veterans Affairs, Salt Lake City, UT.
⁴ Department of Medicine, University of Utah School of Medicine, Salt Lake City, UT.
⁵ Tennessee Valley Healthcare System, Veterans Affairs Medical Center, Nashville, TN.
⁶ Department of Biomedical Informatics, Vanderbilt University Medical Center, Nashville, TN.
⁷ Department of Biomedical Informatics, Columbia University Irving Medical Center, New York, NY.
⁸ Division of Pediatric Endocrinology, Diabetes, and Metabolism, Department of Pediatrics, Columbia University Irving Medical Center, New York, NY.
⁹ Centre for Safe Medication Practice and Research, Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
¹⁰ Laboratory of Data Discovery for Health (D24H), Hong Kong Science Park, Hong Kong, China.
¹¹ Research Department of Practice and Policy, School of Pharmacy, University College London, London, U.K.
¹² Centre for Medicines Optimisation Research and Education, University College London Hospitals NHS Foundation Trust, London, U.K.
¹³ Department of Biostatistics, Fielding School of Public Health, University of California, Los Angeles, CA.
¹⁴ Division of Endocrinology, Diabetes, and Metabolism, Johns Hopkins University School of Medicine, Baltimore, MD.
¹⁵ Faculty of Medicine, O'Brien Institute for Public Health, University of Calgary, Calgary, Alberta, Canada.
¹⁶ Department of Biostatistics, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD.
¹⁷ Department of Epidemiology and Biostatistics, Peking University, Beijing, China.
¹⁸ DTA&AI, Real World Solutions, IQVIA, Durham, NC.
¹⁹ Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA.
²⁰ Section of Cardiovascular Medicine, Department of Internal Medicine, Yale University, New Haven, CT.
²¹ Real-World Epidemiology Research Group, Fundaci Institut Universitari per a la recerca a l'Atenci Primria de Salut Jordi Gol i Gurina, Barcelona, Spain.
²² Observational Health Data Analytics, Janssen Research and Development, LLC, Titusville, NJ.
²³ Epidemiology, Office of the Chief Medical Officer, Johnson & Johnson, Titusville, NJ.
²⁴ Center for Outcomes Research and Evaluation, Yale New Haven Hospital, New Haven, CT.
²⁵ Department of Health Policy and Management, Yale School of Public Health, New Haven, CT.
²⁶ Section of Health Informatics, Department of Biostatistics, Yale School of Public Health, New Haven, CT.
²⁷ Department of Biomathematics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA.
²⁸ Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA.

PMID: 40465422
PMCID: PMC12281980
DOI: 10.2337/dc25-0154

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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Conflict of interest statement

Duality of Interest. R.K. is an associate editor of the Journal of the American Medical Association and reported receiving support from the Doris Duke Charitable Foundation. He also receives research support through Yale from Bristol-Myers Squibb, Novo Nordisk, and BridgeBio. He is a coinventor of U.S. Provisional Patent Applications 63/619,241; 63/606,203; 63/177,117; 63/346,610; 63/428,569; and 63/484,426 unrelated to the current work. He is also a cofounder of Evidence2Health and Ensight-AI, both representing precision health platforms to improve evidence-based cardiovascular care. S.L.D. reports receiving grants from Alnylam Pharmaceuticals, Inc.; AstraZeneca Pharmaceuticals LP; Biodesix, Inc.; Celgene Corporation; Cerner Enviza; GSK PLC; Janssen Pharmaceuticals, Inc.; Novartis International AG; and Parexel International Corporation through the University of Utah or Western Institute for Veteran Research outside the submitted work. K.K.C.M. reported receiving support through a Maplethorpe Fellowship and the National Institute of Health Research, U.K.; European Commission Framework Horizon 2020; Hong Kong Research Grant Council; and Innovation and Technology Commission of the Hong Kong Special Administration Region Government outside the submitted work. In the past 3 years, H.M.K. received expenses and/or personal fees from UnitedHealth, Element Science, Aetna, Reality Labs, Tesseract/4Catalyst, F-Prime, the Siegfried and Jensen Law Firm, Arnold and Porter Law Firm, and Martin/Baughman Law Firm. He is a cofounder of Refactor Health and HugoHealth and is associated with contracts, through Yale New Haven Hospital, from the Centers for Medicare & Medicaid Services and through Yale University from Johnson & Johnson. No other potential conflicts of interest relevant to this article were reported.

Figures

**Figure 1**
Schematic of new-user cohort design to study thyroid tumor with second-line treatments for T2DM. Dx, diagnosis; Rx, prescription.

See this image and copyright information in PMC

References

1. Drucker DJ. Mechanisms of action and therapeutic application of glucagon-like peptide-1. Cell Metab 2018;27:740–756 - PubMed
1. Zinman B, Wanner C, Lachin JM, et al.; EMPA-REG OUTCOME Investigators . Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med 2015;373:2117–2128 - PubMed
1. Wiviott SD, Raz I, Sabatine MS, et al. Dapagliflozin and cardiovascular outcomes in type 2 diabetes. Reply. N Engl J Med 2019;380:1881–1882 - PubMed
1. Neal B, Perkovic V, Matthews DR, et al. Canagliflozin and cardiovascular and renal events in type 2 diabetes. N Engl J Med 2017;377:2099. - PubMed
1. Marso SP, Bain SC, Consoli A, et al.; SUSTAIN-6 Investigators . Semaglutide and cardiovascular outcomes in patients with type 2 diabetes. N Engl J Med 2016;375:1834–1844 - PubMed

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

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

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Conflict of interest statement

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