DIRECT (Diabetes Incidence after
Renal Transplantation:
Neoral C(2) Monitoring Versus
Tacrolimus) was a 6-month, open-label, randomized, multicenter study which used American Diabetes Association/World Health Organization criteria to define
glucose abnormalities. De novo renal transplant patients were randomized to
cyclosporine microemulsion (CsA-ME, using C(2) monitoring) or
tacrolimus, with
mycophenolic acid,
steroids and
basiliximab. The intent-to-treat population comprised 682 patients (336 CsA-ME, 346
tacrolimus): 567 were nondiabetic at baseline. Demographics, diabetes risk factors and
steroid doses were similar between treatment groups. The primary safety endpoint, new-onset diabetes after transplant (NODAT) or impaired fasting
glucose (IFG) at 6 months, occurred in 73 CsA-ME patients (26.0%) and 96
tacrolimus patients (33.6%, p = 0.046). The primary efficacy endpoint, biopsy-proven acute rejection, graft loss or death at 6 months, occurred in 43 CsA-ME patients (12.8%) and 34
tacrolimus patients (9.8%, p = 0.211). Mean glomerular filtration rate (Cockcroft-Gault) was 63.6 +/- 20.7 mL/min/1.73 m(2) in the CsA-ME cohort and 65.9 +/- 23.1 mL/min/1.73 m(2) with
tacrolimus (p = 0.285); mean serum
creatinine was 139 +/- 58 and 133 +/- 57 mumol/L, respectively (p = 0.005). Blood pressure was similar between treatment groups at month 6, but total
cholesterol, LDL-
cholesterol and
triglyceride levels were significantly higher with CsA than with
tacrolimus (total
cholesterol:HDL remained unchanged). The profile and incidence of adverse events were similar between treatments. The incidence of NODAT or IFG at 6 months post-transplant is significantly lower with CsA-ME than with
tacrolimus without a significant difference in short-term outcome.