Prevention of Diabetes After Transplantation by Vildagliptin in the Early Post-transplant Period
Status:
Recruiting
Trial end date:
2021-12-01
Target enrollment:
Participant gender:
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.
Phase:
Phase 3
Details
Lead Sponsor:
Centre Hospitalier Universitaire de Besancon
Collaborators:
Amiens University Hospital Centre Hospitalier Universitaire de Nice Recherche Clinique Paris Descartes Necker Cochin Sainte Anne Rennes University Hospital Tenon Hospital, Paris University Hospital, Brest University Hospital, Lille University Hospital, Strasbourg, France University Hospital, Tours