Is it safe to initiate a GLP-1 (Glucagon-like peptide-1) receptor agonist, such as liraglutide (Victoza) or semaglutide (Ozempic), in a 46-year-old female patient with an unbiopsied thyroid nodule?

GLP-1 Receptor Agonists Should Be Avoided in Patients with Unbiopsied Thyroid Nodules

You were correct to deny GLP-1 therapy for a 46-year-old female with an unbiopsied thyroid nodule, as GLP-1 receptor agonists are not recommended in patients at risk for thyroid tumors.

Thyroid Safety Concerns with GLP-1 Receptor Agonists

GLP-1 receptor agonist treatment is specifically not recommended in patients at risk for thyroid C-cell tumors based on theoretical risks from preclinical models 1. This includes:

• Patients with a personal or family history of medullary thyroid carcinoma
• Patients with multiple endocrine neoplasia syndrome type 2 (MEN2)
• Patients with undiagnosed thyroid nodules that haven't been evaluated

The 2024 Anaesthesia guideline clearly states that GLP-1 receptor agonists carry contraindications for patients with a personal or family history of medullary thyroid cancer 1. The American College of Cardiology also lists these as absolute contraindications 1.

Risk Assessment for Thyroid Nodules

For your patient:

• The nodule has not been biopsied yet
• The nature of the nodule (benign vs. malignant) is unknown
• Without proper evaluation, it's impossible to rule out medullary thyroid cancer or other malignancies

Recent Evidence on GLP-1 RAs and Thyroid Cancer

A 2025 study found that despite the low absolute risk of thyroid cancer among patients receiving GLP-1 receptor agonist therapy, there was a significantly increased risk of new thyroid cancer diagnoses within the first year of GLP-1 receptor agonist initiation compared to other diabetes drugs (HR 1.85; 95% CI 1.11-3.08) 2. This suggests a potential association that warrants caution.

Case Report Evidence

A 2024 case report documented suppressed thyroid stimulating hormone levels after initiation of subcutaneous semaglutide in a post-thyroidectomy patient managed with levothyroxine 3. This indicates that GLP-1 RAs may affect thyroid function, which is particularly concerning in a patient with an existing thyroid abnormality.

Clinical Decision Algorithm

1. For patients with unbiopsied thyroid nodules:

   • Defer GLP-1 RA therapy until proper evaluation
   • Complete thyroid nodule workup including biopsy
   • Rule out medullary thyroid cancer and other malignancies

2. If biopsy confirms benign nodule:

   • Reassess eligibility for GLP-1 RA therapy
   • Consider alternative weight loss or diabetes management options if any uncertainty remains

3. If biopsy shows malignancy or is indeterminate:

   • Absolutely avoid GLP-1 RA therapy
   • Pursue appropriate thyroid cancer management
   • Consider alternative medications for weight loss or diabetes management

Alternative Options

For patients with thyroid nodules who need weight management or diabetes control:

• Metformin (if diabetes is the concern)
• SGLT2 inhibitors (if appropriate for the patient's condition)
• Lifestyle modifications including diet and exercise
• Behavioral interventions for weight management
• Consider bariatric surgery for severe obesity if appropriate

Conclusion

Your decision to deny GLP-1 receptor agonist therapy for this patient with an unbiopsied thyroid nodule was appropriate and aligned with current guidelines. The potential risk of stimulating thyroid C-cell growth or affecting thyroid function outweighs the benefits until proper evaluation of the nodule is completed.