Safety of Ozempic (Semaglutide) in Patients with Neuroendocrine Tumors
Ozempic (semaglutide) should be avoided in patients with neuroendocrine tumors (NETs) due to potential risks of tumor growth stimulation and worsening of hormonal symptoms.
Mechanism of Concern
Semaglutide is a glucagon-like peptide-1 (GLP-1) receptor agonist that works by binding to GLP-1 receptors. Recent research has shown that certain neuroendocrine neoplasms express GLP-1 receptors, and treatment with semaglutide can promote tumor growth in these cases 1.
Key findings from research include:
- 50% of neuroendocrine cell lines tested expressed GLP-1 receptors
- Semaglutide treatment increased growth by 19-22% in GLP-1R-expressing NET cell lines
- In animal models, semaglutide promoted tumor growth by 72% in NET xenografts 1
Specific Concerns by NET Type
Insulinomas
- Insulinomas are particularly problematic with medications that affect glucose metabolism
- Similar to octreotide (another peptide hormone analog), semaglutide could potentially worsen hypoglycemia in patients with insulinoma
- The NCCN guidelines specifically warn against medications that suppress counterregulatory hormones in insulinoma patients 2, 3
Other Functional NETs
- For patients with other functional NETs (gastrinomas, glucagonomas, VIPomas), somatostatin analogs are the established first-line therapy for controlling hormonal symptoms 2
- Adding semaglutide could potentially interfere with the established treatment regimens and symptom control
Risk-Benefit Assessment
Potential Risks:
- Tumor growth stimulation in GLP-1R-expressing NETs 1
- Interference with established NET treatments
- Possible worsening of hormonal symptoms, especially in insulinomas
- Unpredictable effects on tumor secretory function
Alternative Options:
- For glycemic control in NET patients with diabetes, other antidiabetic medications with established safety profiles in NET patients should be considered
- Somatostatin analogs remain the first-line therapy for controlling both symptoms and tumor growth in functional NETs 2
Special Considerations
Thyroid C-cell Tumors
- Semaglutide carries a boxed warning regarding the risk of thyroid C-cell tumors based on animal studies 4
- While the human relevance is uncertain, this raises additional concerns for patients already diagnosed with one type of neuroendocrine tumor
Monitoring Recommendations
If semaglutide must be used in a patient with NET (when benefits clearly outweigh risks):
- Regular monitoring of tumor markers specific to the patient's NET type
- More frequent imaging to assess for tumor progression
- Close monitoring of hormonal symptoms
- Immediate discontinuation if any evidence of tumor growth or worsening symptoms
Conclusion
Based on the available evidence, particularly the recent research showing promotion of tumor growth in GLP-1R-expressing NETs 1, and considering the established treatment pathways for NETs that prioritize somatostatin analogs 2, semaglutide should be avoided in patients with neuroendocrine tumors. Alternative glucose-lowering medications should be considered for NET patients who also have diabetes.