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

GLP-1 Receptor Agonists in Patients with History of Thyroid Cancer

GLP-1 receptor agonists are contraindicated in patients with a personal or family history of medullary thyroid carcinoma and in patients with multiple endocrine neoplasia syndrome type 2, as stated in FDA Black Box Warnings. 1

Contraindications and Risk Assessment

• GLP-1 receptor agonists carry an FDA Black Box Warning regarding the risk of thyroid C-cell tumors, making them contraindicated in patients with a personal or family history of medullary thyroid carcinoma (MTC) and in patients with multiple endocrine neoplasia syndrome type 2 1
• Even with microdosing approaches, GLP-1 receptor agonists should be used with caution in patients with a history of thyroid C-cell tumors 2
• Patients at risk for thyroid C-cell tumors should not use GLP-1 receptor agonists due to safety concerns 3

Evidence on Thyroid Cancer Risk

• A 2023 nested case-control study using the French national health care insurance system found increased risk of all thyroid cancer (adjusted HR 1.58,95% CI 1.27-1.95) and medullary thyroid cancer (adjusted HR 1.78,95% CI 1.04-3.05) with GLP-1 RA use for 1-3 years 4
• A 2025 analysis found an increased risk of new thyroid cancer diagnoses within the first year of GLP-1RA initiation compared to other diabetes drugs (HR, 1.85; 95% CI, 1.11-3.08), though the absolute risk remained low 5
• Conversely, a 2025 international multisite cohort study found no evidence that GLP-1RA use is associated with increased risk of thyroid cancer with follow-up ranging from 1.8 to 3.0 years (pooled weighted HR 0.81, CI 0.59-1.12) 6
• A 2024 narrative review concluded that evidence from randomized controlled trials indicates occurrence of thyroid cancer is infrequent in individuals exposed to GLP-1 RA, with no conclusive evidence of elevated thyroid cancer risk 7

Clinical Decision-Making Algorithm

1. Assess thyroid cancer history:

   • If patient has history of medullary thyroid carcinoma or family history of MTC: Absolutely contraindicated 1, 3
   • If patient has multiple endocrine neoplasia syndrome type 2: Absolutely contraindicated 1
   • If patient has history of other types of thyroid cancer (non-MTC):

2. For non-MTC thyroid cancer history:

   • Consider time since complete remission
   • Evaluate risk/benefit ratio based on:
     • Need for glycemic control
     • Presence of cardiovascular or renal disease that might benefit from GLP-1 RA therapy
     • Availability of alternative therapies 8

3. If considering GLP-1 RA despite history of non-MTC thyroid cancer:

   • Implement close monitoring with regular thyroid function tests
   • Consider microdosing approach to minimize potential risks while maintaining benefits 2
   • Start with the lowest possible dose and titrate slowly 2, 3
   • Monitor for any signs or symptoms of thyroid abnormalities 3

Alternative Treatment Options

• For patients with thyroid cancer history where GLP-1 RAs are contraindicated, consider:
  • SGLT-2 inhibitors (especially for patients with heart failure or chronic kidney disease) 8
  • DPP-4 inhibitors (with appropriate dose adjustments for renal function) 1
  • Metformin as first-line therapy 1
  • Insulin therapy when necessary for glycemic control 1

Important Caveats

• The absolute risk of thyroid cancer with GLP-1 RA use appears to be low, but the evidence is still evolving 7, 5
• Short-term studies (1.8-3.0 years) show no significant increased risk, but long-term effects remain uncertain 6
• The increased detection of thyroid cancer in the first year of GLP-1 RA use may be due to enhanced surveillance rather than true causation 5
• Patients should be informed about the potential risks and the importance of reporting any symptoms related to thyroid abnormalities 3