Vildagliptin and Pioglitazone in Patients With Impaired Glucose Tolerance After Kidney Transplantation: A Randomized, Placebo-Controlled Clinical Trial

Background. New-onset diabetes after transplantation (NODAT) is a serious complication after kidney transplantation affecting graft and patient survival. Currently, no guidelines exist for the management of renal transplant patients with impaired glucose tolerance (IGT), a risk factor for the development of NODAT and an independent predictor of death. Methods. In a population of 48 stable renal transplant recipients at least 6 months from time of transplantation with newly diagnosed IGT, we tested the dipeptidylpeptidase-4 inhibitor vildagliptin, the thiazolidinedione pioglitazone, or placebo for 3 months in addition to lifestyle counseling. Outcome measures were difference in change in oral glucose tolerance test between the groups and between baseline and end of study as well as change in HbA1c, serum lipids, and renal and hepatic function. Results. In both treatment groups, 2-hr plasma glucose at 3 months was significantly reduced compared with baseline (vildagliptin: -20 +/- 24 mg/dL; P=0.002 and pioglitazone: -23 +/- 29 mg/dL; P=0.004), and pioglitazone also significantly improved fasting plasma glucose (-11 +/- 14 mg/dL; P=0.003), although the primary outcome (difference in change in 2-hr plasma glucose among the three groups) did not reach statistical significance. Furthermore, HbA1c was decreased in both treatment arms (vildagliptin: -0.1%+/- 0.3%; P=0.046 and pioglitazone: -0.2%+/- 0.3%; P=0.029). In the placebo group, no significant changes in these parameters were observed. Only mild adverse events occurred and at a similar rate in all three groups. Conclusions. These data demonstrate that both vildagliptin and pioglitazone are of potential benefit in patients with IGT after renal transplantation in addition to lifestyle modification.