Prospective, multicenter, randomized trial to compare incidence of new-onset diabetes mellitus and glucose metabolism in patients receiving cyclosporine microemulsion versus tacrolimus after de novo kidney transplantation

Transplant Proc. 2005 Mar;37(2):1001-4. doi: 10.1016/j.transproceed.2004.12.017.


New-onset diabetes mellitus (NODM) is associated with increased risk of graft failure and death in renal transplant recipients. Some clinical studies have indicated that NODM risk is higher with tacrolimus than cyclosporine, but no comparative trial has used American Diabetic Association (ADA)/World Health Organization (WHO) criteria for diagnosis of diabetes mellitus. The Diabetes Incidence After Renal Transplantation, Neoral C2 Monitoring Versus Tacrolimus (DIRECT) study is a 6-month open-label, multicenter trial comparing the impact of tacrolimus and Neoral (cyclosporine microemulsion) on glucose metabolism in 700 de novo kidney transplant recipients, based on ADA/WHO criteria. Patients are randomized to tacrolimus (C0 monitoring) or Neoral (C2 monitoring), stratified by baseline diabetic status and ethnicity. All patients receive basiliximab, corticosteroids, and mycophenolate mofetil or enteric-coated mycophenolate acid (myfortic). Pooled interim 3-month results from a subset of 115 patients receiving either tacrolimus or Neoral showed that the primary efficacy end-point (biopsy-proven acute rejection [BPAR], graft loss or death) occurred in 11 patients (10%). There were four graft losses and only one death, which occurred after graft loss. Eight patients experienced BPAR (7.3%). Among 99 patients who were nondiabetic at baseline, 14 developed NODM by month 3, 17 developed impaired fasting glucose or impaired glucose tolerance, and another 5 patients received hypoglycemic treatment for at least 14 consecutive days or at the month 3 visit, resulting in a 36% incidence of impaired glucose metabolism. At 3 months, median GFR (Nankivell) was 63.7 mL/min; median serum creatinine was 137 micromol/L. Full complete results are expected in December 2005.

Publication types

  • Clinical Trial
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adrenal Cortex Hormones / therapeutic use
  • Adult
  • Body Weight / drug effects
  • Cyclosporine / administration & dosage
  • Cyclosporine / pharmacokinetics
  • Cyclosporine / therapeutic use*
  • Diabetes Mellitus / epidemiology*
  • Drug Monitoring
  • Drug Therapy, Combination
  • European Continental Ancestry Group
  • Female
  • Humans
  • Immunosuppressive Agents / therapeutic use
  • Kidney Transplantation / adverse effects
  • Kidney Transplantation / immunology*
  • Male
  • Middle Aged
  • Mycophenolic Acid / therapeutic use
  • Reoperation / statistics & numerical data
  • Tacrolimus / administration & dosage
  • Tacrolimus / adverse effects*
  • Tacrolimus / pharmacokinetics
  • Tissue Donors / statistics & numerical data
  • Treatment Failure
  • United States


  • Adrenal Cortex Hormones
  • Immunosuppressive Agents
  • Cyclosporine
  • Mycophenolic Acid
  • Tacrolimus