GLP-1 Receptor Agonists and the Risk of Thyroid Cancer
Abstract
OBJECTIVE: To determine whether use of glucagon-like peptide 1 (GLP-1) receptor agonists (RA) is associated with increased risk of thyroid cancer. RESEARCH DESIGN AND METHODS: A nested case-control analysis was performed with use of the French national health care insurance system (SNDS) database. Individuals with type 2 diabetes treated with second-line antidiabetes drugs between 2006 and 2018 were included in the cohort. All thyroid cancers were identified through hospital discharge diagnoses and medical procedures between 2014 and 2018. Exposure to GLP-1 RA was measured within the 6 years preceding a 6-month lag-time period and considered as current use and cumulative duration of use based on defined daily dose (≤1, 1 to 3, >3 years). Case subjects were matched with up to 20 control subjects on age, sex, and length of diabetes with the risk-set sampling procedure. Risk of thyroid cancer related to use of GLP-1 RA was estimated with a conditional logistic regression with adjustment for goiter, hypothyroidism, hyperthyroidism, other antidiabetes drugs, and social deprivation index. RESULTS: A total of 2,562 case subjects with thyroid cancers were included in the study and matched with 45,184 control subjects. Use of GLP-1 RA for 1-3 years was associated with increased risk of all thyroid cancer (adjusted hazard ratio [HR] 1.58, 95% CI 1.27-1.95) and medullary thyroid cancer (adjusted HR 1.78, 95% CI 1.04-3.05). CONCLUSIONS: In the current study we found increased risk of all thyroid cancer and medullary thyroid cancer with use of GLP-1 RA, in particular after 1-3 years of treatment.
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Concerns regarding the validity of outcomes have emerged, particularly owing to reliance on indirect indicators such as calcitonin test, carcinoembryonic antigen measurement, or vandetanib treatment to distinguish between MTC and non-MTC, introducing potential misclassification.
“Concerns regarding the validity of outcomes have emerged, particularly owing to the reliance on indirect indicators such as the calcitonin test, carcinoembryonic antigen measurement, or vandetanib treatment to distinguish between MTC and non-MTC. This approach introduces the potential for misclassification.21,25”
From Glucagon-Like Peptide-1 Receptor Agonists and Thyroid Cancer: A Narrative Review (2024) · cites this paper as [25]
In a French nested case-control study, GLP-1 RA use for 1-3 years was associated with increased risk for any thyroid cancer (adjusted HR = 1.58, 95% CI 1.27-1.95).
“GLP-1 RA use for 1–3 years was associated with increased risk for any thyroid cancer (adjusted HR = 1.58 [CI 1.27–1.95]) and MTC (adjusted HR = 1.78 [CI 1.04–3.05]).25”
From Glucagon-Like Peptide-1 Receptor Agonists and Thyroid Cancer: A Narrative Review (2024) · cites this paper as [25]
Five observational studies included analyses considering different lag times for outcome assessment, while two studies provided distinct information differentiating between thyroid cancer in general and MTC.
“In addition, five studies included analyses considering different lag times for outcome assessment, while two studies provided distinct information differentiating between thyroid cancer in general and MTC.25,38,51–53”
From Glucagon-Like Peptide-1 Receptor Agonists and Thyroid Cancer: A Narrative Review (2024) · cites this paper as [25]
In a French nested case-control study, GLP-1 RA use for 1-3 years was associated with increased risk for MTC (adjusted HR = 1.78, 95% CI 1.04-3.05).
“GLP-1 RA use for 1–3 years was associated with increased risk for any thyroid cancer (adjusted HR = 1.58 [CI 1.27–1.95]) and MTC (adjusted HR = 1.78 [CI 1.04–3.05]).25”
From Glucagon-Like Peptide-1 Receptor Agonists and Thyroid Cancer: A Narrative Review (2024) · cites this paper as [25]
There was a large variation in the percentage of cases reported as MTC between the two studies that included this distinction.
“Of note, there was a large variation in the percentage of cases reported as MTC between the two studies that included this distinction.25,38”
From Glucagon-Like Peptide-1 Receptor Agonists and Thyroid Cancer: A Narrative Review (2024) · cites this paper as [25]
Two observational studies reported statistically significant findings of increased risk for thyroid cancer in those exposed to GLP-1 RA.
“Two studies reported statistically significant findings of increased risk for thyroid cancer in those exposed to GLP-1 RA.25,38”
From Glucagon-Like Peptide-1 Receptor Agonists and Thyroid Cancer: A Narrative Review (2024) · cites this paper as [25]
In the French study, 15% of all thyroid cancer cases identified were MTC, which is higher than expected and might be related to methods used for defining MTC.
“Of all thyroid cancer cases identified, 15% were MTC, which is higher than expected and might be related to methods used for defining MTC (e.g., testing for calcitonin test/carcinoembryonic antigen or vandetanib treatment).25”
From Glucagon-Like Peptide-1 Receptor Agonists and Thyroid Cancer: A Narrative Review (2024) · cites this paper as [25]
The potential for residual confounding and the role of surveillance bias are important considerations that have not been thoroughly assessed.
“Similarly, the potential for residual confounding (e.g., limited evaluation of specific risk factors for thyroid cancer such as obesity, neck radiation, and family history of thyroid cancer) and the role of surveillance bias (e.g., clinicians might be more likely to do a thyroid exam or ultrasound on patients taking GLP-1 RA) are important considerations that have been not thoroughly assessed.25,”
From Glucagon-Like Peptide-1 Receptor Agonists and Thyroid Cancer: A Narrative Review (2024) · cites this paper as [25]
In VigiBase, there was a signal of disproportionate reporting of GLP-1 RA and overall thyroid cancer and MTC, including 606 reports (mostly from exenatide and liraglutide).
“Consistent with previous studies, they also found a signal of disproportionate reporting of GLP-1 RA and overall thyroid cancer and MTC, including 606 reports (mostly from exenatide and liraglutide).25”
From Glucagon-Like Peptide-1 Receptor Agonists and Thyroid Cancer: A Narrative Review (2024) · cites this paper as [25]
Recent investigations have highlighted the association between various neoplasms, such as thyroid, breast, and cholangiocarcinoma, and GLP-1 RAs.
“Recent investigations have highlighted the association between various neoplasms, such as thyroid, breast, and cholangiocarcinoma, and GLP-1 RAs [105-107].”
From Exploring the Side Effects of GLP-1 Receptor Agonist: To Ensure Its Optimal Positioning (2025) · cites this paper as [107]
Bezin et al. found that GLP-1 RA use for 1-3 years was associated with a heightened risk of all thyroid cancers, adjusted HR 1.58 (95% CI 1.27-1.95), and medullary thyroid cancer, adjusted HR 1.78 (95% CI 1.04-3.05).
“the use of GLP-1 RAs for a duration of 1–3 years was associated with a heightened risk of all thyroid cancers, presenting an adjusted hazard ratio of 1.58 (95% CI 1.27–1.95) and an adjusted HR of 1.78 (95% CI 1.04–3.05), specifically for medullary thyroid cancer.”
A case-control study of health insurance data from France indicated an increased risk for thyroid carcinoma with GLP-1RA treatment, with an HR of 1.58 (95% CI 1.27-1.95).
“A case-control study of health insurance data from France indicated an increased risk for thyroid carcinoma with GLP-1RA treatment, with an HR of 1.58 (95% CI 1.27–1.95) (78).”
From The science of safety: adverse effects of GLP-1 receptor agonists as glucose-lowering and obesity medications (2026) · cites this paper as [78]
Recent health insurance data from France indicate an elevated risk of medullary thyroid carcinoma in individuals treated with GLP-1RAs versus other glucose-lowering agents (35 cases, HR 1.78, 95% CI 1.04-3.05).
“Recent health insurance data from France are indicative of an elevated risk of medullary thyroid carcinoma in individuals treated with GLP-1RAs versus other glucose-lowering agents (35 cases, hazard ratio [HR] 1.78 [95% CI 1.04–3.05]) (78).”
From The science of safety: adverse effects of GLP-1 receptor agonists as glucose-lowering and obesity medications (2026) · cites this paper as [78]
In epidemiological studies, a significant association with GLP-1RA treatment could be detected for medullary, but not for papillary, thyroid cancer.
“in epidemiological studies a significant association with GLP-1RA treatment could be detected for medullary, but not for papillary cancer.12”
From Glucagon‐like peptide‐1 receptor agonists and risk of thyroid cancer: A systematic review and meta‐analysis of randomized controlled trials (2024) · cites this paper as [12]
A similar problem affects observational studies; the main survey attempting to discriminate MTC from PTC used indirect markers of limited reliability.
“A similar problem affects observational studies; the main survey attempting to discriminate MTC from PTC 12 used indirect markers of limited reliability.21,22”
From Glucagon‐like peptide‐1 receptor agonists and risk of thyroid cancer: A systematic review and meta‐analysis of randomized controlled trials (2024) · cites this paper as [12]
Analyses of serious adverse events reported to the FDA and the WHO pharmacovigilance database VigiBase confirmed an increased risk of thyroid cancer in association with GLP-1RA treatment.
“which was also confirmed by analyses of serious adverse events reported to the US Food and Drug Administration (FDA) 11,13 and the World Health Organization's pharmacovigilance database Vigi-Base.12,14”
From Glucagon‐like peptide‐1 receptor agonists and risk of thyroid cancer: A systematic review and meta‐analysis of randomized controlled trials (2024) · cites this paper as [12]
Some retrospective observational studies detected an increased risk of thyroid cancer in association with GLP-1RA treatment.
“Some retrospective observational studies detected an increased risk of thyroid cancer in association with GLP-1RA treatment, 11,12”
From Glucagon‐like peptide‐1 receptor agonists and risk of thyroid cancer: A systematic review and meta‐analysis of randomized controlled trials (2024) · cites this paper as [12]
This meta-analysis suggests that GLP-1RA treatment may be associated with a moderate increase in risk of thyroid cancer, not dissimilar in extent from a recent observational study.
“This meta-analysis suggests that GLP-1RA treatment may be associated with a moderate increase in risk of thyroid cancer, not dissimilar in its extent from that reported by a recent observational study, 12”
From Glucagon‐like peptide‐1 receptor agonists and risk of thyroid cancer: A systematic review and meta‐analysis of randomized controlled trials (2024) · cites this paper as [12]
The association between DPP4-i and thyroid cancer might be partly explained by increased endogenous GLP-1 levels after DPP-4 inhibition.
“Also, the use of DPP4-i was found to be associated with a higher risk of thyroid cancer, leading the authors to hypothesize that this association might be partly explained by increased endogenous GLP-1 levels after the inhibition of DPP-4 [132].”
From Adipose Tissue: A Novel Target of the Incretin Axis? A Paradigm Shift in Obesity-Linked Insulin Resistance (2024) · cites this paper as [132]
Using GLP-1 RAs increased the risk of both medullary thyroid cancer and thyroid cancer overall, in particular after 1-3 years of treatment exposure, especially for male subjects.
“The results showed that using GLP-1 RAs increased the risk of both medullary thyroid cancer and thyroid cancer overall, in particular after 1–3 years of treatment exposure (especially for male subjects) [132].”
From Adipose Tissue: A Novel Target of the Incretin Axis? A Paradigm Shift in Obesity-Linked Insulin Resistance (2024) · cites this paper as [132]
Use of DPP4-i was found to be associated with a higher risk of thyroid cancer.
“Also, the use of DPP4-i was found to be associated with a higher risk of thyroid cancer, leading the authors to hypothesize that this association might be partly explained by increased endogenous GLP-1 levels after the inhibition of DPP-4 [132].”
From Adipose Tissue: A Novel Target of the Incretin Axis? A Paradigm Shift in Obesity-Linked Insulin Resistance (2024) · cites this paper as [132]
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- Authors
- Bezin, J., Gouverneur, A., Pénichon, M., Mathieu, C., Garrel, R., Hillaire-Buys, D., Pariente, A., & Faillie, J.-L.
- Affiliations
- Université de Bordeaux (FR)
- Centre Hospitalier Universitaire de Montpellier (FR)
- 4Département de Pharmacologie Médicale et Toxicologie, Centre Hospitalier Universitaire de Montpellier, Montpellier, France
- Inserm (FR)
- Corresponding author
- Faillie, Jean-Luc
- Venue
- Diabetes Care
- Publisher
- American Diabetes Association
- Published
- 2022-11-10
- Volume
- 46
- Issue
- 2
- Pages
- 384-390
- ISSN
- 0149-5992 (ISSN-L)
- 1935-5548
- OpenAlex
- W4308701204
- Cited by
- 320
- References
- 17
- Citations by year
- 2026: 64 · 2025: 118 · 2024: 94 · 2023: 42 · 2022: 2
- FWCI
- 47.40
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Diabetes Care (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- Oskar-Bordeaux (Universite de Bordeaux) (submittedVersion)
- Funders
- Agence Nationale de Sécurité du Médicament et des Produits de Santé (2019S015)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Cancer Diagnosis and Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Keywords
- GLP-1 receptor agonists, thyroid cancer, medullary thyroid carcinoma, type 2 diabetes, drug safety, cancer risk, treatment duration
- MeSH terms
- Glucagon-Like Peptide-1 Receptor Agonists, Diabetes Mellitus, Type 2, Humans, Hypoglycemic Agents, Thyroid Neoplasms, Glucagon-Like Peptide 1
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