Significantly improved graft function following exenatide administration in pancreas transplant recipients with chronic allograft dysfunction

J.N. Walker¹, R. Craven-Todd¹, J.C. Levy¹, S. Gough¹, S. Sinha², P. Friend², E. Sharples², A. Vaidya^2
1 Oxford Centre for Diabetes, Endocrinology and Metabolism, Oxford, U.K.; ² Oxford Transplant Centre, Oxford, U.K.

Objective: Exenatide, a glucagon like peptide-1 (GLP-1) receptor agonist, has been used successfully in islet transplant patients to improve graft function. Here we report the potential benefits of this therapy in pancreas transplant patients with chronic allograft dysfunction.

Methods: Three subjects with type 1 diabetes mellitus who had successfully undergone simultaneous kidney/ pancreas transplantation were selected. Pancreas allograft dysfunction was detected at a median of 50months (range 10-60months) requiring exogenous insulin; renal function had remained stable. Patients were initially started on exenatide 5mcg od and if tolerated the dose was increased to a maximal dose of 10mcg bd. HbA1c, insulin requirements and stimulated c-peptide following a mixed-meal tolerance test (MMTT) were used as determinants of graft outcome at baseline and 20weeks post-treatment. Body weight was recorded before and after treatment.

Results: All patients continued exenatide for the 20week period. After this time, insulin requirements had reduced significantly {p<0.05} and stimulated c-peptide 90mins following a MMTT had increased significantly {p<0.05}. The mean HbA1c reduced but this was not significant. 2/3 patients lost >5% body weight.

Conclusion: This is the first study that demonstrates the positive effect of exenatide therapy on failing whole organ pancreas grafts, significantly reducing the need for exogenous insulin. For the treatment of pancreas allograft dysfunction incretin-based therapies could be used prior to the initiation of insulin therapy, however further studies are needed to determine at what stage intervention would be most beneficial.