Can a patient with a non-functioning metastatic pancreatic neuroendocrine tumor (pNET) that is not Multiple Endocrine Neoplasia type 1 (MEN1) related take Mounjaro (tirzepatide)?

Mounjaro (Tirzepatide) Use in Non-Functioning Metastatic pNET

Mounjaro (tirzepatide) should be avoided in patients with non-functioning metastatic pancreatic neuroendocrine tumors due to the theoretical risk of tumor stimulation via GLP-1 receptor pathways and lack of safety data in this specific population.

Critical Safety Considerations

Theoretical Pancreatic Tumor Risk

• GLP-1 receptor agonists, including tirzepatide (which has dual GIP/GLP-1 activity), carry theoretical concerns about pancreatic neuroendocrine tumor development based on preclinical data
• While your patient's pNET is not MEN1-related, the presence of an established metastatic neuroendocrine malignancy creates a different risk-benefit calculation than using tirzepatide for diabetes or weight loss in the general population
• No clinical trial data exists specifically evaluating tirzepatide safety in patients with existing pancreatic neuroendocrine tumors 1, 2

Lack of Evidence in pNET Population

• Current pNET management guidelines from NCCN, ENETS, and ESMO do not address the use of incretin-based therapies in this population 3
• The focus of non-functioning metastatic pNET management is on somatostatin analogs, molecular targeted agents (everolimus, sunitinib), chemotherapy (capecitabine-temozolomide), and peptide receptor radionuclide therapy 3, 4
• No guideline recommends or evaluates GLP-1 receptor agonists as part of the therapeutic armamentarium 3

Alternative Approaches for Metabolic Management

If Diabetes Management is the Goal

• Somatostatin analogs (octreotide, lanreotide) are the cornerstone of therapy for metastatic non-functioning pNETs and should already be considered as first-line treatment, particularly if the tumor is somatostatin receptor imaging (SRI) positive 3, 4
• These agents provide both tumor control and can help manage any metabolic derangements
• For G1 or G2 tumors with Ki-67 <10%, SSAs are specifically recommended as first-line therapy 3

If Weight Management is the Primary Concern

• Weight management should be secondary to oncologic control in metastatic disease
• Focus should be on multidisciplinary NET management including surgical debulking if feasible, molecular targeted therapy, or PRRT depending on disease characteristics 3, 5, 4

Clinical Decision Algorithm

Step 1: Assess Current pNET Management

• Ensure patient is under care of NET-dedicated multidisciplinary team 5
• Verify somatostatin receptor imaging status (Gallium-68 PET/CT preferred) 5
• Confirm tumor grade (Ki-67 index) and current treatment regimen 3, 4

Step 2: Evaluate Indication for Tirzepatide

• If for diabetes: Consider alternative agents (metformin, SGLT2 inhibitors, insulin) that lack theoretical pancreatic tumor concerns
• If for weight loss: Defer until oncologic stability is achieved, if ever
• If patient already has well-controlled metastatic disease on SSAs, adding tirzepatide introduces unnecessary theoretical risk 3

Step 3: Risk-Benefit Assessment

• The potential metabolic benefits of tirzepatide do not outweigh the theoretical oncologic risks in a patient with established metastatic pancreatic neuroendocrine malignancy
• Quality of life and mortality considerations favor avoiding agents with uncertain safety profiles in this population 5

Key Pitfalls to Avoid

• Do not prioritize metabolic management over oncologic safety in patients with active metastatic neuroendocrine malignancy 5
• Do not assume safety data from general diabetes populations applies to patients with existing pancreatic neuroendocrine tumors 1, 2
• Do not use tirzepatide without explicit discussion with the patient's NET multidisciplinary team including medical oncology and endocrinology 5

Bottom Line

In the absence of safety data and given theoretical concerns about GLP-1 pathway stimulation in patients with existing pancreatic neuroendocrine tumors, tirzepatide should not be used. Alternative metabolic management strategies exist that do not carry these theoretical risks. The primary therapeutic focus should remain on established pNET treatments including somatostatin analogs, molecular targeted agents, chemotherapy, or PRRT as appropriate for the patient's specific tumor characteristics 3, 4.