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 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

doi:10.2337/dc25-0154

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 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 (Lead / Corresponding author)

Population Health and Genomics

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25 Downloads (Pure)

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.

Original language	English
Pages (from-to)	1386-1394
Number of pages	9
Journal	Diabetes Care
Volume	48
Issue number	8
Early online date	4 Jun 2025
DOIs	https://doi.org/10.2337/dc25-0154
Publication status	Published - 1 Aug 2025

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

Humans
Thyroid Neoplasms/epidemiology
Female
Retrospective Studies
Male
Middle Aged
Glucagon-Like Peptide-1 Receptor Agonists
Diabetes Mellitus Type 2/drug therapy
Hypoglycemic Agents/therapeutic use
Aged
Dipeptidyl-Peptidase IV Inhibitors/therapeutic use
Sodium-Glucose Transporter 2 Inhibitors/therapeutic use

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Morales, D. R., Bu, F., Viernes, B., DuVall, S. L., Matheny, M. E., Simon, K. R., Falconer, T., Richter, L. R., Ostropolets, A., Lau, W. C. Y., Man, K. K. C., Chattopadhyay, S., Mathioudakis, N., Minty, E., Nishimura, A., Sun, F., Yin, C., Seager, S. L., Chai, Y., ... Suchard, M. A. (2025). Risk of Thyroid Tumors With GLP-1 Receptor Agonists: A Retrospective Cohort Study. Diabetes Care, 48(8), 1386-1394. https://doi.org/10.2337/dc25-0154

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title = "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 [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.",

keywords = "Humans, Thyroid Neoplasms/epidemiology, Female, Retrospective Studies, Male, Middle Aged, Glucagon-Like Peptide-1 Receptor Agonists, Diabetes Mellitus Type 2/drug therapy, Hypoglycemic Agents/therapeutic use, Aged, Dipeptidyl-Peptidase IV Inhibitors/therapeutic use, Sodium-Glucose Transporter 2 Inhibitors/therapeutic use",

author = "Morales, \{Daniel R\} and Fan Bu and Benjamin Viernes and DuVall, \{Scott L\} and Matheny, \{Michael E\} and Simon, \{Katherine R\} and Thomas Falconer and Richter, \{Lauren R\} and Anna Ostropolets and Lau, \{Wallis C Y\} and Man, \{Kenneth K C\} and Shounak Chattopadhyay and Nestoras Mathioudakis and Evan Minty and Akihiko Nishimura and Feng Sun and Can Yin and Seager, \{Sarah L\} and Yi Chai and Zhou, \{Jin J\} and Yuan Lu and Carlen Reyes and Andrea Pistillo and Talita Duarte-Salles and Clair Blacketer and Schuemie, \{Martijn J\} and Ryan, \{Patrick B\} and Krumholz, \{Harlan M\} and George Hripcsak and Rohan Khera and Suchard, \{Marc A\}",

note = "{\textcopyright} 2025 by the American Diabetes Association.",

year = "2025",

month = aug,

day = "1",

doi = "10.2337/dc25-0154",

language = "English",

volume = "48",

pages = "1386--1394",

journal = "Diabetes Care",

issn = "0149-5992",

publisher = "American Diabetes Association Inc.",

number = "8",

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Morales, DR, Bu, F, Viernes, B, DuVall, SL, Matheny, ME, Simon, KR, Falconer, T, Richter, LR, Ostropolets, A, Lau, WCY, Man, KKC, Chattopadhyay, S, Mathioudakis, N, Minty, E, Nishimura, A, Sun, F, Yin, C, Seager, SL, Chai, Y, Zhou, JJ, Lu, Y, Reyes, C, Pistillo, A, Duarte-Salles, T, Blacketer, C, Schuemie, MJ, Ryan, PB, Krumholz, HM, Hripcsak, G, Khera, R & Suchard, MA 2025, 'Risk of Thyroid Tumors With GLP-1 Receptor Agonists: A Retrospective Cohort Study', Diabetes Care, vol. 48, no. 8, pp. 1386-1394. https://doi.org/10.2337/dc25-0154

TY - JOUR

T1 - Risk of Thyroid Tumors With GLP-1 Receptor Agonists

T2 - A Retrospective Cohort Study

AU - Morales, Daniel R

AU - Bu, Fan

AU - Viernes, Benjamin

AU - DuVall, Scott L

AU - Matheny, Michael E

AU - Simon, Katherine R

AU - Falconer, Thomas

AU - Richter, Lauren R

AU - Ostropolets, Anna

AU - Lau, Wallis C Y

AU - Man, Kenneth K C

AU - Chattopadhyay, Shounak

AU - Mathioudakis, Nestoras

AU - Minty, Evan

AU - Nishimura, Akihiko

AU - Sun, Feng

AU - Yin, Can

AU - Seager, Sarah L

AU - Chai, Yi

AU - Zhou, Jin J

AU - Lu, Yuan

AU - Reyes, Carlen

AU - Pistillo, Andrea

AU - Duarte-Salles, Talita

AU - Blacketer, Clair

AU - Schuemie, Martijn J

AU - Ryan, Patrick B

AU - Krumholz, Harlan M

AU - Hripcsak, George

AU - Khera, Rohan

AU - Suchard, Marc A

PY - 2025/8/1

Y1 - 2025/8/1

N2 - 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.

AB - 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.

KW - Humans

KW - Thyroid Neoplasms/epidemiology

KW - Female

KW - Retrospective Studies

KW - Male

KW - Middle Aged

KW - Glucagon-Like Peptide-1 Receptor Agonists

KW - Diabetes Mellitus Type 2/drug therapy

KW - Hypoglycemic Agents/therapeutic use

KW - Aged

KW - Dipeptidyl-Peptidase IV Inhibitors/therapeutic use

KW - Sodium-Glucose Transporter 2 Inhibitors/therapeutic use

UR - https://www.scopus.com/pages/publications/105012136373

U2 - 10.2337/dc25-0154

DO - 10.2337/dc25-0154

M3 - Article

C2 - 40465422

SN - 0149-5992

VL - 48

SP - 1386

EP - 1394

JO - Diabetes Care

JF - Diabetes Care

IS - 8

ER -

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

Abstract

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Keywords

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