GLP-1 Receptor Agonists and Thyroid Cancer Risk
GLP-1 receptor agonists are absolutely contraindicated in patients with a personal or family history of medullary thyroid carcinoma (MTC) or Multiple Endocrine Neoplasia syndrome type 2 (MEN2), but current evidence does not support a clinically significant increased risk of thyroid cancer in the general population using these medications. 1, 2, 3
The Rodent Data vs. Human Evidence Gap
The FDA black box warning stems from animal studies showing dose-dependent thyroid C-cell tumors (adenomas and carcinomas) in rats and mice at clinically relevant exposures. 4 However, the human relevance of these rodent findings has not been established. 4 This biological plausibility exists in rodents but is far less clear for humans, particularly for non-medullary thyroid cancers. 5
What the Clinical Evidence Actually Shows
Randomized Controlled Trials
- Thyroid cancer is a rare event in RCTs of GLP-1 receptor agonists, with no conclusive or consistent evidence of increased risk. 5
- In adult glycemic control trials, there were 7 cases of papillary thyroid carcinoma in liraglutide-treated patients versus 1 case in comparator-treated patients (1.5 vs. 0.5 cases per 1,000 patient-years). 4
- Most of these papillary thyroid carcinomas were <1 cm in diameter and were diagnosed after thyroidectomy prompted by protocol-specified screening with serum calcitonin or thyroid ultrasound. 4
Large-Scale Observational Studies
The evidence from observational studies is mixed and inconsistent:
A 2025 multisite international cohort study (the highest quality recent evidence) including 98,147 GLP-1 RA users and 2,488,303 DPP-4i users found no association between GLP-1 RA use and thyroid cancer risk (pooled weighted HR 0.81,95% CI 0.59-1.12). 6 This study had median follow-up ranging from 1.8 to 3.0 years across six population-based databases. 6
A 2025 US study found increased risk within the first year after GLP-1 RA initiation (HR 1.85,95% CI 1.11-3.08), but this was likely due to enhanced early detection rather than true increased cancer development. 7
A 2023 French study found increased risk after 1-3 years of treatment (adjusted HR 1.58,95% CI 1.27-1.95 for all thyroid cancer; adjusted HR 1.78,95% CI 1.04-3.05 for medullary thyroid cancer). 8
A 2021 US study found that liraglutide cases had smaller thyroid nodules (67% were microcarcinomas ≤10mm versus 43% in comparators) and shorter time-to-diagnosis, suggesting surveillance bias. 9 After adjusting for latency, no significant elevated risk was observed. 9
The Surveillance Bias Problem
A critical issue confounding the data is detection bias. 7, 9 Patients starting GLP-1 receptor agonists may undergo more frequent medical monitoring, leading to earlier detection of pre-existing small thyroid cancers. 9 The predominance of microcarcinomas (<1 cm) in GLP-1 RA users strongly suggests this phenomenon. 4, 9
Absolute Contraindications in Clinical Practice
Do not prescribe GLP-1 receptor agonists to patients with: 1, 2, 3, 4
- Personal history of medullary thyroid carcinoma
- Family history of medullary thyroid carcinoma
- Multiple Endocrine Neoplasia syndrome type 2 (MEN2)
- History of serious hypersensitivity reaction to the specific GLP-1 RA
Patient Counseling Requirements
Counsel all patients starting GLP-1 receptor agonists about: 4
- The potential risk for MTC (though human relevance is uncertain)
- Symptoms of thyroid tumors: neck mass, dysphagia, dyspnea, persistent hoarseness
- The need to report these symptoms immediately
Monitoring Recommendations
Routine monitoring of serum calcitonin or thyroid ultrasound is of uncertain value and is NOT recommended for early detection of MTC in patients treated with GLP-1 receptor agonists. 4 Such monitoring may increase the risk of unnecessary procedures due to low test specificity for serum calcitonin and high background incidence of thyroid disease. 4
However, if serum calcitonin is measured and significantly elevated (usually >50 ng/L in MTC patients), further evaluation is warranted. 4 Patients with thyroid nodules noted on physical examination or neck imaging should also be further evaluated. 4
Clinical Bottom Line
The absolute risk of thyroid cancer with GLP-1 receptor agonists remains very low. 7, 5 The most recent and highest quality evidence from 2025 shows no increased risk with short-to-medium term use (up to 3 years). 6 Earlier signals of increased risk appear largely attributable to surveillance bias and enhanced detection of pre-existing small cancers. 7, 9
The proven cardiovascular and metabolic benefits of GLP-1 receptor agonists in appropriate patients substantially outweigh the unproven thyroid cancer risk in those without personal or family history of MTC or MEN2. 1 Excessive concern about unproven thyroid cancer risk should not lead to underutilization of these highly effective medications in patients who could otherwise experience substantial benefits. 5
Key Caveat
Evidence remains insufficient to rule out excess risk with very long-term use (>3 years) due to limited follow-up duration in current studies. 6, 5