Is it safe to prescribe tirzepatide (a glucagon-like peptide-1 (GLP-1) receptor agonist) to a patient with hypothyroidism?

Can Tirzepatide Be Given to a Patient with Hypothyroidism?

Yes, tirzepatide can be safely prescribed to patients with hypothyroidism, as hypothyroidism itself is not a contraindication to tirzepatide use. However, you must ensure the patient does not have a personal or family history of medullary thyroid cancer (MTC) or multiple endocrine neoplasia syndrome type 2 (MEN2), which are absolute contraindications 1, 2, 3.

Absolute Contraindications to Screen For

Before prescribing tirzepatide to any patient, including those with hypothyroidism, you must exclude:

• Personal or family history of medullary thyroid cancer (MTC) 1, 2, 3
• Multiple endocrine neoplasia syndrome type 2 (MEN2) 1, 2, 3
• Pregnancy or breastfeeding 2, 3

These contraindications stem from animal studies showing thyroid C-cell tumors with GLP-1 receptor agonists, though human relevance remains uncertain 2, 3.

Hypothyroidism-Specific Considerations

Hypothyroidism is NOT a contraindication to tirzepatide. In fact, recent real-world evidence from Saudi Arabia involving 47,017 patients found that GLP-1 receptor agonist use was not associated with increased incidence of hypothyroidism compared to DPP-4 inhibitors (adjusted HR 1.04,95% CI 0.69-1.57) 4. The incidence rate of hypothyroidism was actually numerically lower in GLP-1RA users (128 per 10,000 person-years) compared to DPP-4i users (150 per 10,000 person-years) 4.

Monitoring Recommendations for Patients with Hypothyroidism

While you can safely prescribe tirzepatide to patients with hypothyroidism, implement the following monitoring strategy:

• Ensure thyroid function is optimized before starting treatment with adequate levothyroxine replacement 3
• Monitor thyroid function during therapy, particularly if the patient experiences symptoms suggestive of thyroid dysfunction 3
• Check TSH and free T4 at baseline and periodically during treatment (every 3-6 months initially) 3
• Be aware that GLP-1 receptors are expressed in the thyroid, which may explain some pleiotropic effects, though clinical significance in patients with pre-existing hypothyroidism is minimal 3

Clinical Context: Why This Question Matters

The concern about thyroid effects with GLP-1 receptor agonists stems from preclinical rodent studies showing thyroid C-cell hyperplasia and tumors 4. However, this has not translated to increased thyroid cancer risk in humans 2, 3. The FDA black box warning is based on animal data, not human evidence 2.

In clinical trials of tirzepatide, hypothyroidism events (all grade 1 or 2) occurred in approximately 8.1% of patients on similar GLP-1 agonists, typically identified early and managed with medical therapy 2. These were generally mild and did not require treatment discontinuation 2.

Practical Prescribing Algorithm

For a patient with hypothyroidism requesting tirzepatide:

1. Screen for absolute contraindications: Ask specifically about personal/family history of MTC or MEN2 1, 2, 3
2. Verify thyroid function is controlled: Check recent TSH/free T4 to ensure adequate levothyroxine replacement 3
3. Assess eligibility criteria: BMI ≥30 kg/m² or BMI ≥27 kg/m² with weight-related comorbidity 3
4. Initiate standard tirzepatide dosing: Start at 5 mg weekly subcutaneously 1, 3
5. Titrate every 4 weeks: Increase to 10 mg, then 15 mg weekly based on tolerance and efficacy 1, 3
6. Monitor thyroid function: Check TSH/free T4 at 3-6 months, then as clinically indicated 3

Common Pitfalls to Avoid

• Do not withhold tirzepatide solely because of hypothyroidism – this is not a contraindication 4
• Do not confuse hypothyroidism with MTC/MEN2 – only the latter are absolute contraindications 1, 2, 3
• Do not assume GLP-1 receptor agonists worsen thyroid function – real-world evidence shows no increased hypothyroidism risk 4
• Do not forget to optimize levothyroxine dosing before starting tirzepatide – uncontrolled hypothyroidism may confound weight loss assessment 3

Expected Outcomes

Patients with well-controlled hypothyroidism on levothyroxine can expect the same benefits from tirzepatide as patients without thyroid disease:

• Weight loss: 20.9% at 72 weeks with tirzepatide 15 mg weekly 1, 3
• Glycemic control: HbA1c reductions of 1.87-2.59% in patients with type 2 diabetes 3
• Cardiovascular benefits: Improved blood pressure, lipid profiles, and reduced cardiovascular events 1, 3

The presence of hypothyroidism does not diminish these benefits, provided thyroid hormone replacement is adequate 3, 4.