Is it safe to give tirzepatide (glucagon-like peptide-1 receptor agonist) to a patient with a history of hypothyroidism and papillary thyroid carcinoma?

Can Tirzepatide Be Given to a Patient with Hypothyroidism and Papillary Carcinoma?

Yes, tirzepatide can be safely administered to patients with hypothyroidism and a history of papillary thyroid carcinoma, as the contraindication for GLP-1/GIP receptor agonists applies specifically to medullary thyroid carcinoma (MTC), not papillary thyroid cancer. 1

Understanding the Contraindication

The FDA black box warning for tirzepatide is explicit and limited in scope:

• Tirzepatide is contraindicated only in patients with a personal or family history of medullary thyroid carcinoma (MTC) or Multiple Endocrine Neoplasia syndrome type 2 (MEN 2). 1
• This contraindication stems from rodent studies showing thyroid C-cell tumors, which are the cells of origin for MTC, not papillary thyroid cancer. 1
• Papillary thyroid carcinoma is NOT listed as a contraindication in the FDA labeling. 1

Evidence Supporting Safety in Papillary Thyroid Cancer

Guideline Recommendations

• The American College of Physicians and National Comprehensive Cancer Network confirm that GLP-1 receptor agonists or dual GIP/GLP-1 receptor agonists like tirzepatide are not contraindicated in patients with a history of papillary thyroid cancer. 2
• The European Society for Medical Oncology states that tirzepatide can be utilized in patients with differentiated thyroid carcinoma (which includes papillary thyroid cancer) without history of MTC or MEN-2. 3

Clinical Trial Data

• A 2025 meta-analysis of 13 RCTs with 13,761 participants found identical cancer risks between tirzepatide and control groups over 26-72 weeks, with no cases of papillary thyroid carcinoma reported despite increases in serum calcitonin with higher doses. 4
• A 2024 meta-analysis of phase 2/3 RCTs in type 2 diabetes found tirzepatide does not increase risk for any cancer type, including thyroid cancer. 5
• A 2024 narrative review concluded there is no conclusive evidence of elevated thyroid cancer risk with GLP-1 receptor agonists, with thyroid cancer being a rare event in randomized trials. 6

Management Considerations for Your Patient

Prerequisites Before Starting Tirzepatide

Patients should have completed appropriate initial treatment for their papillary thyroid cancer and be enrolled in an appropriate surveillance program based on their risk category. 2

• The American Thyroid Association and European Society for Medical Oncology recommend risk stratification (very low-risk, low-risk, intermediate-risk, and high-risk categories) with corresponding surveillance strategies. 2, 7

Monitoring Requirements

• Continue standard thyroid cancer surveillance as recommended based on the patient's risk category; no additional monitoring is required specifically due to tirzepatide use. 2
• For disease-free patients at low risk for recurrence, TSH should be maintained either slightly below or slightly above the lower limit of the reference range. 8
• For intermediate-risk patients, mild TSH suppression (0.1-0.5 mIU/mL) may be considered. 8
• High-sensitivity thyroglobulin assays and neck ultrasound remain the primary surveillance tools for papillary thyroid cancer, independent of tirzepatide use. 7

Hypothyroidism Management

• Levothyroxine dosing may require adjustment when initiating tirzepatide, as drug-drug interactions are possible. 7
• Monitor thyroid function tests (TSH and free T4) after 6-8 weeks of starting tirzepatide and adjust levothyroxine accordingly. 8
• Tirzepatide delays gastric emptying and has the potential to impact absorption of concomitantly administered oral medications, including levothyroxine. 1

Important Caveats

What to Avoid

• Do not confuse papillary thyroid carcinoma with medullary thyroid carcinoma - they are distinct entities with different cells of origin (follicular cells vs. C-cells). 1
• Do not order unnecessary calcitonin monitoring in papillary thyroid cancer patients, as calcitonin is a marker for MTC, not papillary cancer. 7

When to Exercise Caution

• While GLP-1 receptor expression has been detected in 18% of papillary thyroid carcinomas in research studies, the clinical significance of this finding remains unknown. 9, 10
• High-risk papillary thyroid cancer patients may warrant more careful discussion, though there is no evidence that tirzepatide increases recurrence risk. 2

Practical Algorithm for Decision-Making

1. Confirm the thyroid cancer type is papillary (not medullary) - review pathology reports. 1
2. Verify no personal or family history of MTC or MEN-2 - if present, tirzepatide is absolutely contraindicated. 1
3. Ensure papillary thyroid cancer has been appropriately treated and patient is in surveillance phase. 2
4. Assess current thyroid cancer risk category (low, intermediate, or high-risk) and confirm appropriate surveillance is in place. 2, 8
5. Optimize levothyroxine dosing before starting tirzepatide to achieve appropriate TSH target for risk category. 8
6. Initiate tirzepatide at standard dosing (2.5 mg weekly, titrating as indicated). 1
7. Monitor thyroid function 6-8 weeks after starting and adjust levothyroxine if needed. 8
8. Continue standard thyroid cancer surveillance without additional testing related to tirzepatide. 2