What adjustments should be made to the medication regimen for a patient with a history of pancreatic neuroendocrine tumor (NET) on lanreotide (somatostatin analogue) with worsening glucose control, currently on metformin (biguanide) 2000 mg/day and acarbose (alpha-glucosidase inhibitor) 25 mg three times a day?

From the Guidelines

For a patient with pancreatic NET on lanreotide who is experiencing worsening glucose control despite metformin 2000 mg/day and acarbose 25 mg TID, I recommend increasing the acarbose dose to 50-100 mg TID with meals while maintaining the current metformin dose. Additionally, consider adding a DPP-4 inhibitor such as sitagliptin 100 mg daily or a GLP-1 receptor agonist like semaglutide (starting at 0.25 mg weekly, titrating to 0.5-1.0 mg weekly) 1. The patient should have more frequent blood glucose monitoring (at least twice daily) and HbA1c checked every 3 months. This approach addresses the complex glucose dysregulation caused by the interaction between lanreotide and pancreatic function. Lanreotide, as a somatostatin analogue, inhibits insulin and glucagon secretion, which can worsen glucose control. The current acarbose dose is subtherapeutic, as typical effective doses range from 50-100 mg TID. DPP-4 inhibitors or GLP-1 receptor agonists are preferred additional agents as they work through incretin pathways that may be less affected by somatostatin analogues. SGLT-2 inhibitors could be considered as an alternative if the patient has normal renal function and no history of diabetic ketoacidosis. Sulfonylureas should be avoided as they may be less effective with impaired insulin secretion from lanreotide therapy.

Some key points to consider in the management of this patient's glucose control include:

• The importance of monitoring and adjusting the medication regimen to achieve optimal glucose control
• The potential benefits of adding a DPP-4 inhibitor or GLP-1 receptor agonist to the patient's medication regimen
• The need to avoid sulfonylureas due to their potential decreased effectiveness in the setting of lanreotide therapy
• The consideration of SGLT-2 inhibitors as an alternative option if the patient has normal renal function and no history of diabetic ketoacidosis

It is also important to note that the patient's glucose control should be closely monitored, with frequent blood glucose checks and regular HbA1c measurements, to ensure that the chosen medication regimen is effective and to make any necessary adjustments. The most recent and highest quality study, 1, provides guidance on the management of glucose control in patients with pancreatic NET on lanreotide, and should be consulted for further information.

From the FDA Drug Label

In diabetic non-acromegalic subjects receiving a continuous infusion (21-day) of lanreotide, serum glucose concentrations were temporarily decreased by 20% to 30% after the start and end of the infusion. The patient's glucose control has worsened with each dose of lanreotide, with waking glucose now between 140-160 and averaging 135. Given the patient is currently on metformin 2000 mg/day and acarbose 25 mg three times a day, adjustments to the medication regimen should be made to improve glucose control.

• Consider increasing the dose of metformin or acarbose, or
• Adding another antidiabetic medication to the regimen. However, the FDA drug label does not provide specific guidance on managing worsening glucose control in patients with pancreatic neuroendocrine tumors on lanreotide. Therefore, caution should be exercised, and the patient's glucose control should be closely monitored. 2

From the Research

Medication Adjustments for Worsening Glucose Control

The patient's current medication regimen includes lanreotide 120 mg, metformin 2000 mg/day, and acarbose 25 mg three times a day. To address the worsening glucose control, the following adjustments could be considered:

• Monitoring and adjusting the dosage of metformin and acarbose to optimize their efficacy in controlling blood glucose levels 3
• Considering alternative somatostatin analogues, such as octreotide, which may have a different effect on glucose control compared to lanreotide 4
• Evaluating the patient's response to lanreotide and adjusting the treatment plan accordingly, as some patients may experience improvements in glucose control while others may experience worsening glucose control 3

Somatostatin Analogues and Glucose Control

Somatostatin analogues, such as lanreotide and octreotide, can have varying effects on glucose control:

• Lanreotide may worsen glucose control in some patients, particularly those with diabetes 3, 4
• Octreotide may improve glucose control in some patients, particularly those with hyperinsulinism 4, 5
• The effects of somatostatin analogues on glucose control may be related to their binding affinity for specific somatostatin receptor subtypes 4

Additional Considerations

Other factors that may influence glucose control in this patient include:

• The use of other medications that may affect glucose control, such as fluoxetine, which has been associated with hypoglycemia in some patients 6
• The patient's underlying condition, including the history of pancreatic neuroendocrine tumor and liver metastasis, which may impact glucose control and response to treatment 7, 3