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Peer-reviewedCC BYInternational journal of medical sciences

Association of GLP-1 Receptor Agonist Use with Thyroid Outcomes in Adults with Type 2 Diabetes.

  • Ching-Chung Hsiao1,2,3
  • Ming-Hsien Tsai4,5,6
  • Jian-Yu Jhu7
  • Ya-Fang Liu6
  • Chieh-Li Yen2,3,8
  • Jia-Jin Chen2,3,8
  • Pei-Chi Chen7
8 affiliations
  1. 1Department of Nephrology, New Taipei Municipal Tu Cheng Hospital, New Taipei City, Taiwan.
  2. 2College of Medicine, Chang Gung University, Taoyuan, Taiwan.
  3. 3Kidney Research Center, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan.
  4. 4Division of Nephrology, Department of Internal Medicine, Shin-Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan.
  5. 5Department of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan.
  6. 6Data Analytics Group, Department of Digital Medicine, Shin-Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan.
  7. 7Division of Endocrinology and Metabolism, Department of Internal Medicine, Shin-Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan.
  8. 8Department of Nephrology, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan.
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Abstract

Background

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are widely used to treat type 2 diabetes mellitus, but their associations with thyroid disorders remain uncertain. We evaluated whether initiating a GLP-1 RA, compared with initiating a dipeptidyl peptidase-4 inhibitor (DPP-4i), was associated with newly recorded autoimmune thyroiditis and other thyroid outcomes.Methods

This new-user, active-comparator cohort study emulated a target trial using the TriNetX Collaborative Network. Adults with type 2 diabetes who initiated a GLP-1 RA or DPP-4i between January 1, 2018, and December 31, 2022, and had no prior use of either drug class were eligible. Patients with pre-existing thyroid disease, any neoplasm, immunosuppressant or immunostimulant use, transplantation, or end-stage kidney disease or dialysis were excluded. Propensity score matching yielded 107,912 patients per group. The primary outcome was newly recorded autoimmune thyroiditis; secondary outcomes were nontoxic uninodular goiter, nontoxic multinodular goiter, and thyroid malignancy. Cox models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs), with false discovery rate adjustment. Follow-up extended from 1 day after treatment initiation to 4 years.Results

Autoimmune thyroiditis occurred in 524 GLP-1 RA users (0.49%) and 417 DPP-4i users (0.39%). GLP-1 RA initiation was associated with a higher risk of autoimmune thyroiditis (HR, 1.26; 95% CI, 1.11-1.43; FDR-adjusted P = 0.002). Modestly higher risks were also observed for nontoxic uninodular goiter (HR, 1.07; 95% CI, 1.01-1.13) and nontoxic multinodular goiter (HR, 1.11; 95% CI, 1.03-1.19). The risk of thyroid malignancy did not differ significantly (HR, 0.93; 95% CI, 0.77-1.12). Findings were generally consistent across sensitivity and subgroup analyses, although heterogeneity was observed across body mass index strata.Conclusion

Among adults with type 2 diabetes, GLP-1 RA initiation was associated with small increases in newly recorded autoimmune thyroiditis and benign nodular thyroid disease, but not with thyroid malignancy. Given the small absolute differences and the potential for residual confounding and surveillance bias, these findings require validation in future studies.

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Cite

BibTeXRIS
BibTeX
@article{hsiao2026association,
  title = {{Association of GLP-1 Receptor Agonist Use with Thyroid Outcomes in Adults with Type 2 Diabetes.}},
  author = {Ching-Chung Hsiao and Ming-Hsien Tsai and Jian-Yu Jhu and Ya-Fang Liu and Chieh-Li Yen and Jia-Jin Chen and Pei-Chi Chen},
  journal = {International journal of medical sciences},
  year = {2026},
  month = oct,
  doi = {10.7150/ijms.141099},
  url = {https://europepmc.org/article/MED/42910111},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Association of GLP-1 Receptor Agonist Use with Thyroid Outcomes in Adults with Type 2 Diabetes.
AU  - Ching-Chung Hsiao
AU  - Ming-Hsien Tsai
AU  - Jian-Yu Jhu
AU  - Ya-Fang Liu
AU  - Chieh-Li Yen
AU  - Jia-Jin Chen
AU  - Pei-Chi Chen
PY  - 2026
DA  - 2026/10/02
JO  - International journal of medical sciences
DO  - 10.7150/ijms.141099
UR  - https://europepmc.org/article/MED/42910111
AB  - Background  Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are widely used to treat type 2 diabetes mellitus, but their associations with thyroid disorders remain uncertain. We evaluated whether initiating a GLP-1 RA, compared with initiating a dipeptidyl peptidase-4 inhibitor (DPP-4i), was associated with newly recorded autoimmune thyroiditis and other thyroid outcomes.Methods  This new-user, active-comparator cohort study emulated a target trial using the TriNetX Collaborative Network. Adults with type 2 diabetes who initiated a GLP-1 RA or DPP-4i between January 1, 2018, and December 31, 2022, and had no prior use of either drug class were eligible. Patients with pre-existing thyroid disease, any neoplasm, immunosuppressant or immunostimulant use, transplantation, or end-stage kidney disease or dialysis were excluded. Propensity score matching yielded 107,912 patients per group. The primary outcome was newly recorded autoimmune thyroiditis; secondary outcomes were nontoxic uninodular goiter, nontoxic multinodular goiter, and thyroid malignancy. Cox models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs), with false discovery rate adjustment. Follow-up extended from 1 day after treatment initiation to 4 years.Results  Autoimmune thyroiditis occurred in 524 GLP-1 RA users (0.49%) and 417 DPP-4i users (0.39%). GLP-1 RA initiation was associated with a higher risk of autoimmune thyroiditis (HR, 1.26; 95% CI, 1.11-1.43; FDR-adjusted P = 0.002). Modestly higher risks were also observed for nontoxic uninodular goiter (HR, 1.07; 95% CI, 1.01-1.13) and nontoxic multinodular goiter (HR, 1.11; 95% CI, 1.03-1.19). The risk of thyroid malignancy did not differ significantly (HR, 0.93; 95% CI, 0.77-1.12). Findings were generally consistent across sensitivity and subgroup analyses, although heterogeneity was observed across body mass index strata.Conclusion  Among adults with type 2 diabetes, GLP-1 RA initiation was associated with small increases in newly recorded autoimmune thyroiditis and benign nodular thyroid disease, but not with thyroid malignancy. Given the small absolute differences and the potential for residual confounding and surveillance bias, these findings require validation in future studies.
SN  - 1449-1907
ER  -