Exenatide may improve glucose control in recipients of islet cell transplants

Exenatide may be associated with prolonged islet function following transplantation.

Issue: August 2006

WASHINGTON – Exenatide may be a new key in improving outcomes for patients with type 1 diabetes who have received islet cell transplants. A new study, conducted by Canadian researchers and presented at the American Diabetes Association’s 66th Annual Scientific Sessions, held in Washington in June, found that exenatide (Byetta, Amylin) might be associated with increases in prolonged islet function following transplantation.

In recent years, islet cell transplantation has received much medical and media attention and has been heralded as a potentially significant therapeutic advancement for type 1 diabetes treatment. Recent studies have shown that islet cell transplantation may help to eliminate the severe hypoglycemia associated with type 1 diabetes. But studies have also shown mixed results for long-term outcomes following islet cell transplantation because islet function declines over time.

Glycemic control

In many patients who have received islet cell transplants, once islet cell function decline begins, pharmacotherapy must be restarted to maintain glycemic control. However, islet grafts typically respond poorly to oral hypoglycemic agents, even though the patient’s C-peptide levels may be normal and show a good response to stimuli such as arginine. This makes treating patients in this population difficult.

Previous studies have shown that glucagon-like peptide (GLP) may stimulate insulin secretion in patients who received islet cell transplants. Exenatide is a GLP analog that has been shown to lower glucose levels in patients with type 2 diabetes and does not produce hypoglycemia when used alone. The researchers of this study wanted to examine whether exenatide would have similar benefits for patients who had had an islet cell transplant.

In patients

The researchers recruited 11 patients with type 1 diabetes who had received an islet cell transplantation. All patients had experienced secondary graft failure but remained C-peptide positive.

The patients were given exenatide at a dose of 5 ucg twice daily for one month. This was followed by two months of exenatide at a dose of 1 ucg twice daily. According to the researchers, glucose levels had become elevated in two of the 11 patients. These patients responded to exenatide with a reduction in glucose levels and remained off insulin for the three months of exenatide treatment.

The remaining nine patients had restarted insulin and eight had a detectable response to exenatide. Insulin requirements dropped an average of 50% during the first month of exenatide treatment but then gradually climbed and were about 75% of the pretreatment dose after three months of exenatide.

According to the researchers, most patients noted glucose lowering for two to four hours after an exenatide injection. This was followed by a gradual rise, corresponding to the half-life of exenatide. Hypoglycemia did not occur in patients on exenatide alone. Adverse events in all patients included significant nausea, though this was expected.

Significant findings

“I was pleased with the results, although not surprised since our preliminary studies using native GLP-1 indicated that the islets would respond,” David Thompson, MD, clinical assistant professor and division head of the department of endocrinology and metabolism at the University of British Columbia in Vancouver and one of the study’s researchers, told Endocrine Today. “From this initial study, it appears that most islet recipients given exenatide can expect to benefit.”

Thompson said this study was only the beginning and more research of this topic was needed. “We know that exenatide works by stimulating insulin secretion in the transplanted islets,” he said. “What is unknown is whether exenatide can maintain or improve islet mass. Animal studies indicate that it can, but they have used higher doses than are used in people and I do not believe that anyone has performed a dose-response study with respect to islet mass,” he said.

“The next studies will likely address the optimal timing and duration of exenatide therapy in islet recipients.” – by Jay Lewis

For more information:

Thompson DM, Fung MA, Meneilly GS, et al. Exenatide improves glucose control in islet cell transplant recipients. Presented at: The American Diabetes Association’s 66th Annual Scientific Sessions; June 9-13, 2006; Washington.