Can patients with a history of thyroid cancer take Glucagon-like peptide-1 (GLP-1) receptor agonists?

GLP-1 Receptor Agonists and History of Thyroid Cancer

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 may be considered with caution in patients with a history of non-medullary thyroid cancer (such as papillary or follicular thyroid cancer) who are in complete remission. 1

Absolute Contraindications

The FDA Black Box Warning establishes clear contraindications for GLP-1 receptor agonists 1:

• Personal history of medullary thyroid carcinoma (MTC) - Do not prescribe under any circumstances 1
• Family history of medullary thyroid carcinoma - Do not prescribe under any circumstances 1
• Multiple endocrine neoplasia syndrome type 2 (MEN2) - Do not prescribe under any circumstances 1

These contraindications are based on preclinical rodent studies demonstrating C-cell tumor development, and this guidance is consistently reinforced by the American Heart Association, American College of Cardiology, and American Diabetes Association 1.

Non-MTC Thyroid Cancer History

For patients with a history of differentiated thyroid cancer (papillary, follicular, or other non-medullary types), the decision requires careful assessment 1:

Risk-Benefit Assessment Algorithm

1. Verify complete remission status - Confirm the patient has achieved complete remission with undetectable thyroglobulin and negative imaging 1

2. Evaluate time since remission - Consider the duration since achieving complete remission; longer disease-free intervals favor consideration of GLP-1 RA therapy 1

3. Assess clinical need - Determine the urgency of glycemic control or weight management and whether cardiovascular or renal benefits outweigh theoretical risks 1

4. Implement enhanced monitoring - If proceeding with GLP-1 RA therapy, establish regular thyroid function testing and clinical surveillance 1

Important Caveats About Thyroid Cancer Risk

Recent evidence presents conflicting data regarding GLP-1 RAs and thyroid cancer risk:

• A 2025 multisite international cohort study found no increased risk of thyroid cancer with GLP-1 RA use compared to DPP-4 inhibitors (pooled HR 0.81,95% CI 0.59-1.12), though follow-up was limited to 1.8-3.0 years 2

• However, a 2025 US claims database study showed increased risk within the first year of GLP-1 RA initiation (HR 1.85,95% CI 1.11-3.08), possibly due to enhanced detection rather than causation 3

• A 2023 French study reported increased risk after 1-3 years of treatment (adjusted HR 1.58,95% CI 1.27-1.95 for all thyroid cancer) 4

• Randomized controlled trials show thyroid cancer as a rare event without conclusive evidence of increased risk 5

The inconsistency in observational data suggests detection bias may play a significant role, as patients on GLP-1 RAs receive more frequent medical surveillance 5.

Alternative Treatment Options

When GLP-1 RAs are contraindicated or declined, consider these alternatives 1:

• SGLT-2 inhibitors - Provide cardiovascular and renal protection without thyroid cancer concerns 1
• DPP-4 inhibitors - Safe alternative for glycemic control 1
• Metformin - First-line therapy recommended by the American Diabetes Association 1
• Insulin therapy - When intensive glycemic control is required 1

Patient Counseling Requirements

Patients considering GLP-1 RA therapy must be informed about 1:

• The importance of reporting any neck mass, hoarseness, dysphagia, or dyspnea
• The theoretical thyroid cancer risk based on animal studies
• The need for ongoing thyroid surveillance if therapy is initiated
• Alternative treatment options available

Monitoring Protocol for Non-MTC Patients

If GLP-1 RA therapy is initiated in a patient with prior non-MTC thyroid cancer 1:

• Continue routine thyroid function monitoring as clinically indicated
• Maintain regular follow-up with endocrinology
• Perform clinical neck examination at each visit
• Consider thyroid ultrasound surveillance per existing thyroid cancer follow-up protocols
• Maintain low threshold for investigating new thyroid symptoms

The absolute risk of thyroid cancer remains low even in exposed populations, but the contraindication for MTC/MEN2 history must be strictly observed 3, 5.