What cancers are contraindications for starting Glucagon-Like Peptide (GLP) therapy?

Contraindications for GLP-1 Receptor Agonist Therapy

GLP-1 receptor agonist therapy is absolutely contraindicated in patients with active gastrointestinal malignancies, medullary thyroid carcinoma (MTC), multiple endocrine neoplasia syndrome type 2 (MEN2), or any active or recent malignancy (within 5 years), regardless of cancer type or location. 1, 2

Cancer-Related Contraindications

Absolute Contraindications:

• Active gastrointestinal malignancies - GLP-1 receptor agonists can enhance growth of colonic and gastrointestinal polyps and potentially accelerate cancer growth 1
• Personal history of medullary thyroid carcinoma (MTC) 2
• Family history of MTC 2
• Multiple Endocrine Neoplasia syndrome type 2 (MEN2) 2
• Any active or recent malignancy (within 5 years), regardless of location 1

Mechanism of Concern

GLP-1 receptor agonists function as growth factors and have intestinotrophic effects that can potentially:

• Enhance growth of existing gastrointestinal polyps
• Accelerate cancer growth in patients with active malignancies
• Stimulate C-cell proliferation in the thyroid (observed in rodent studies) 2, 3

Clinical Evidence Supporting These Contraindications

The American Gastroenterological Association's clinical practice update specifically notes that teduglutide (a GLP-2 analog with similar concerns) should not be used in patients with active or recent malignancy, regardless of location 1. This recommendation stems from observations in the Phase 3 STEPS trial where liver and lung cancers occurred among trial subjects treated with teduglutide 1.

For GLP-1 receptor agonists like semaglutide, there is a black box warning regarding thyroid C-cell tumors observed in rodent studies 2. While human relevance hasn't been definitively determined, caution is warranted given the biological plausibility.

Screening Recommendations Before Initiating Therapy

1. Cancer screening:

   • Colonoscopy before initiating treatment in patients with risk factors for colorectal cancer
   • Periodic colonoscopy monitoring while on therapy 1

2. Thyroid screening:

   • Screen for personal or family history of MTC or MEN2 2
   • Consider baseline thyroid function tests

3. Comprehensive cancer history:

   • Document any history of malignancy within the past 5 years
   • Assess family history of endocrine cancers

Monitoring During Treatment

• Regular monitoring for symptoms of gastrointestinal malignancy
• Periodic colonoscopy for patients at risk of colorectal neoplasia
• Vigilance for thyroid nodules or symptoms of thyroid dysfunction

Recent Research Perspectives

Interestingly, recent research suggests GLP-1 receptor agonists may actually reduce risk of certain obesity-associated cancers compared to insulin therapy, including pancreatic, hepatocellular, colorectal, and several other cancers 4. However, these findings are observational and do not override the established contraindications for patients with active or recent malignancies.

Clinical Decision Algorithm

1. Screen patient for history of any cancer within past 5 years
2. Screen specifically for personal or family history of MTC or MEN2
3. If any positive history → DO NOT PRESCRIBE GLP-1 RECEPTOR AGONISTS
4. If negative cancer history → Proceed with appropriate pre-treatment screening (colonoscopy if indicated)
5. Monitor regularly during treatment

Remember that these contraindications apply to the entire class of GLP-1 receptor agonists, including semaglutide, liraglutide, exenatide, and others, as they share similar mechanisms of action and safety concerns.