GLP-1 Receptor Agonists and Thyroid Cancer Risk
Primary Recommendation
GLP-1 receptor agonists are absolutely contraindicated only in patients with a personal or family history of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia syndrome type 2 (MEN2), but can be safely used in patients with other thyroid conditions including Hashimoto's thyroiditis or history of non-medullary thyroid cancer. 1, 2, 3, 4
Understanding the Contraindication
The FDA Black Box Warning for GLP-1 receptor agonists stems from rodent studies showing thyroid C-cell tumors, but the human relevance remains undetermined. 1, 2 The absolute contraindications are:
- Personal history of medullary thyroid carcinoma 4
- Family history of medullary thyroid carcinoma 4
- Multiple endocrine neoplasia syndrome type 2 (MEN2) 1, 4
Evidence on Thyroid Cancer Risk
Randomized Controlled Trial Evidence
The strongest evidence from randomized trials shows no conclusive increased risk of thyroid cancer with GLP-1 receptor agonist use. 5 Thyroid cancer occurs as a rare event in these trials, making effect estimates imprecise, but without consistent evidence of increased risk. 5
A meta-analysis of 45 randomized controlled trials found that GLP-1 receptor agonists had no significant effect on thyroid cancer occurrence (RR 1.30,95% CI 0.86-1.97). 6
Recent Large-Scale Observational Studies
The most recent 2025 international multisite cohort study involving 98,147 GLP-1 receptor agonist users and 2,488,303 comparator users across six countries found no association between GLP-1 receptor agonist use and increased thyroid cancer risk (pooled weighted HR 0.81,95% CI 0.59-1.12). 7 This study provides reassurance about short-term safety with median follow-up ranging from 1.8 to 3.0 years. 7
A 2025 Korean population-based cohort study of 21,722 GLP-1 receptor agonist users found no increased risk of thyroid cancer compared to SGLT2 inhibitors (weighted HR 0.98,95% CI 0.62-1.53). 8
Important Nuance: Detection Bias
One 2025 study found an increased risk of thyroid cancer diagnoses within the first year of GLP-1 receptor agonist initiation (HR 1.85,95% CI 1.11-3.08), but this likely represents enhanced early detection rather than causation, as the absolute risk remained very low (0.17%). 9 This finding emphasizes that any detected cancers were likely pre-existing rather than caused by the medication. 9
Clinical Decision Algorithm
For Patients WITHOUT MTC/MEN2 History
Proceed with GLP-1 receptor agonist therapy if clinically indicated for type 2 diabetes or obesity management. 3, 4
- Hashimoto's thyroiditis: No additional precautions beyond standard thyroid monitoring required 3
- History of non-MTC thyroid cancer (papillary, follicular, anaplastic): Consider time since remission and implement close monitoring with regular thyroid function tests 4
- Thyroid nodules without cancer: Not a contraindication; proceed with therapy 3
For Patients WITH MTC/MEN2 History
Absolutely do not prescribe GLP-1 receptor agonists. 1, 2, 4 Alternative options include:
- SGLT2 inhibitors for cardiovascular and renal protection 4
- Metformin as first-line therapy 4
- DPP-4 inhibitors 4
- Insulin therapy 4
Pre-Treatment Screening
Before initiating GLP-1 receptor agonist therapy, screen for: 4
- Personal history of medullary thyroid carcinoma
- Family history of medullary thyroid carcinoma
- Multiple endocrine neoplasia syndrome type 2
No routine thyroid imaging or calcitonin testing is required in patients without these risk factors. 3
Monitoring During Treatment
For patients with Hashimoto's thyroiditis or other benign thyroid conditions:
- Continue routine thyroid function monitoring as clinically indicated 3
- Monitor for common GLP-1 receptor agonist adverse effects (nausea up to 44%, diarrhea 13-18%, constipation 10-30%) 3
- No additional thyroid-specific monitoring is required beyond standard care 3
Common Pitfalls to Avoid
Do not withhold GLP-1 receptor agonists from patients with substantial cardiovascular or metabolic benefits due to unwarranted concerns about non-medullary thyroid cancer risk. 5 The evidence does not support increased risk, and excessive worry may lead to underutilization in patients who could experience substantial benefits. 5
Do not perform unnecessary thyroid cancer screening in patients on GLP-1 receptor agonists without MTC/MEN2 risk factors, as this leads to harms from overdiagnosis. 5
Do not confuse the absolute contraindication for MTC/MEN2 with relative concerns about other thyroid conditions—Hashimoto's thyroiditis and non-medullary thyroid cancer history are not contraindications. 3, 4
Balancing Benefits and Theoretical Risks
For patients with type 2 diabetes and established cardiovascular disease, the proven 26% reduction in cardiovascular death, nonfatal MI, or stroke (HR 0.74,95% CI 0.58-0.95) with semaglutide far outweighs any theoretical thyroid cancer risk not supported by current evidence. 1, 2
For patients with obesity, tirzepatide achieves 20.9% weight loss and semaglutide achieves 14.9% weight loss, providing substantial cardiometabolic benefits that should not be foregone based on unproven thyroid cancer concerns. 1, 2