Are GLP-1 (Glucagon-Like Peptide-1) analogues, such as liraglutide (Victoza) or semaglutide (Ozempic), safe for patients with hyperthyroidism?

GLP-1 Analogues in Hyperthyroidism: Safety Considerations

Direct Answer

GLP-1 analogues are NOT contraindicated in patients with hyperthyroidism, but they are absolutely contraindicated in patients with a personal or family history of medullary thyroid cancer (MTC) or multiple endocrine neoplasia syndrome type 2 (MEN2). 1, 2, 3 Hyperthyroidism itself does not appear on any contraindication list for GLP-1 receptor agonists.

Established Contraindications

The only thyroid-related contraindications for GLP-1 analogues are:

• Personal or family history of medullary thyroid carcinoma (MTC) 1, 2, 3
• Multiple endocrine neoplasia syndrome type 2 (MEN2) 1, 2, 3
• History of serious hypersensitivity reaction to the drug 1, 4

Hyperthyroidism (Graves' disease, toxic nodular goiter, thyroiditis) is NOT listed as a contraindication. 1, 2

Thyroid Safety Concerns with GLP-1 Analogues

Medullary Thyroid Cancer Risk

The contraindication stems from animal studies showing that semaglutide and other GLP-1 analogues caused dose-dependent thyroid C-cell tumors (adenomas and carcinomas) in rodents after lifetime exposure at clinically relevant plasma exposures. 3, 5 However, the human relevance of these rodent findings has not been determined. 3

Pharmacovigilance data shows disproportionate reporting of thyroid cancer with GLP-1 analogues:

• Liraglutide: PRR 27.5 (95% CI, 22.7-33.3) 6
• Exenatide: PRR 22.5 (95% CI, 17.9-28.3) 6
• Medullary thyroid cancer specifically: PRR 221.5 (95% CI, 155.7-315.1) 6

GLP-1 Receptors in Thyroid Tissue

GLP-1 receptors are expressed in the thyroid gland, which explains some pleiotropic effects of these medications. 2, 7 This receptor presence does not create a contraindication for hyperthyroidism but necessitates monitoring.

Clinical Algorithm for Hyperthyroid Patients

Pre-Treatment Screening

Before initiating GLP-1 analogues in hyperthyroid patients:

1. Exclude absolute contraindications:

   • Screen for personal or family history of MTC 1, 3
   • Screen for MEN2 syndrome 1, 3
   • Document any history of serious hypersensitivity reactions 1, 4

2. Thyroid assessment:

   • Ensure thyroid function is optimized before starting treatment 7
   • Perform physical examination of the neck for thyroid nodules 3
   • Consider baseline thyroid ultrasound if nodules are palpable 3
   • Baseline serum calcitonin measurement is of uncertain value but may be considered 3

3. Patient counseling:

   • Inform patients about symptoms of thyroid tumors: neck mass, dysphagia, dyspnea, persistent hoarseness 3
   • Explain that routine calcitonin monitoring has uncertain value and may lead to unnecessary procedures 3

Monitoring During Treatment

For hyperthyroid patients on GLP-1 analogues:

• Monitor thyroid function every 3-6 months to ensure hyperthyroidism remains controlled 2, 7
• Physical neck examination at each visit for new thyroid nodules 3
• If serum calcitonin is measured and >50 ng/L, further evaluation is warranted as this may indicate MTC 3
• If thyroid nodules develop, perform appropriate imaging and evaluation 3

Special Considerations for Hyperthyroid Patients

Cardiovascular monitoring is particularly important because:

• GLP-1 analogues can increase heart rate 1
• Hyperthyroidism also increases heart rate and cardiovascular stress
• Monitor blood pressure closely as weight loss may necessitate antihypertensive medication adjustment 2, 7

Medication interactions:

• If the patient is on digoxin for any cardiovascular condition related to hyperthyroidism, closer monitoring is required as hypothyroidism (if treatment causes overcorrection) is a risk factor for digoxin toxicity 7

Common Pitfalls to Avoid

1. Do not confuse hyperthyroidism with MTC/MEN2 - these are completely different conditions with different implications 1, 3

2. Do not unnecessarily withhold GLP-1 analogues based on hyperthyroidism diagnosis alone, as there is no evidence-based contraindication 1, 2

3. Do not rely solely on routine calcitonin monitoring - this has uncertain value and low specificity given the high background incidence of thyroid disease 3

4. Do not ignore cardiovascular status - both hyperthyroidism and GLP-1 analogues affect heart rate, requiring vigilant monitoring 1, 7

Bottom Line

GLP-1 analogues can be safely used in patients with hyperthyroidism, provided there is no personal or family history of medullary thyroid cancer or MEN2 syndrome. 1, 2, 3 Ensure thyroid function is optimized before initiation, monitor cardiovascular parameters closely given the additive effects on heart rate, and counsel patients about thyroid tumor symptoms. 1, 7, 3