prevention of diabetes after transplantation by vildagliptin in the early post-transplant period

Conditions: Disorder Related to Renal Transplantation; Diabetes

Summary: post-transplant diabetes affects 15 to 20% of renal transplant patients and contributes to increased morbidity and reduced survival of transplants and patients. corticosteroids, anti-calcineurin and mammilian target of rapamycin (mtor) inhibitors have a major diabetogenic impact and greatly contribute to the increase in diabetes prevalence after transplantation. there are to date few studies concerning the pharmacological prevention of post-transplant diabetes. hecking et al. have recently reported that a short treatment with insulin, administered immediately after transplantation, reduce the incidence of de novo diabetes one-year post-transplant. this study included 50 renal transplant patients and showed that a three months treatment of (neutral protamine hagedorn) nph insulin decreased hba1c. the occurrence of diabetes, a secondary end-point, was reduced by 73% in the treated group. no further pharmacological strategy has been developed to date. relevant experimental evidences suggest that gliptins could be used in the pharmacological prevention of post-transplant diabetes. these drugs are inhibitors of dipeptidyl peptidase-4 (dpp-4), which inactivates the incretins, the glucagon-like peptide-1 (glp-1) and the gastric inhibitory polypeptide (gip). dpp-4 inhibition causes an increase in the glp-1 and gip concentrations which induce insulin secretion and inhibition of glucagon secretion. the gliptins are approved for the treatment of type 2 diabetes. beyond the effects on blood glucose, gliptins have pleiotropic effects including a protective effect on β cells and anti-inflammatory effect. the additional cost associated with new-onset diabetes after transplantation could be also significantly reduced by efficient prevention. a us study found that, for the period between 1994 and 1998, a newly diagnosed diabetic patient has cost $21,500 of medical expenses 2 years after transplantation. moreover, transplantation resulting in one of the best increases of patients' quality of life, its estimate is essential in the treatment evaluation of this population.


Eligibility criteria:
inclusion criteria: * major patients (18 year old or older) * signature of informed consent * affiliation to a french social security or receiving such a scheme * patient receiving a first kidney transplant * patients considered at high risk of developing posttransplant diabetes having at least 2 of the 3 following criteria: age\> 50 years; bmi greater than 30 kg/m²; direct family history of type 2 diabetes * patients who can receive immunosuppressive therapy including tacrolimus, mycophenolic acid and steroids * patients in whom the cessation of steroids may be considered at the latest at month 3 post-transplant exclusion criteria: * legal disability or limited legal capacity * topic unlikely to cooperate in the study and / or low early cooperation by the investigator * patient without health insurance * pregnancy * patient in the period of exclusion of another study or under the "national register of volunteers." * inability to understand the reasons for the study; psychiatric disorders judged by the investigator to be incompatible with the inclusion in the study * active infection * infection with hepatitis c virus * a history of diabetes * multi-organ transplantation