New-Onset Diabetes After Transplantation (NODAT): An Evaluation of Definitions in Clinical Trials

Background. New-onset diabetes after transplantation (NODAT) occurs commonly. Prior NODAT definitions have been inconsistent. Based on the American Diabetic Association criteria, we propose a new approach to defining NODAT. Methods. Analysis of 1416 at-risk transplant recipients was performed. Data from three de novo Astellas registration transplant studies (two kidney and one liver) evaluated NODAT in 634 at-risk patients receiving tacrolimus, 630 at-risk patients receiving tacrolimus extended release, and 152 at-risk patients receiving cyclosporine. NODAT was defined as a composite endpoint consisting of first occurrence of one of four parameters: (i) two fasting plasma glucose levels >= 126 mg/dL (> 7.0 mmol/L) >= 30 days apart, (ii) oral hypoglycemic agent use for >= 30 consecutive days, (iii) insulin therapy for >= 30 consecutive days, and (iv) hemoglobin A1c >= 6.5%. We evaluated each of the above parameters, as well as the composite endpoint, in an attempt to establish an appropriate clinical approach to the diagnosis of NODAT. Results. The composite definition results in a 1-year NODAT incidence of 30% to 37% in kidney and 44% to 45% in liver transplant recipients treated with tacrolimus. NODAT incidence was significantly higher with tacrolimus than cyclosporine; there was no difference between the two tacrolimus formulations. Conclusions. Based on these analyses, the proposed composite definition for NODAT, incorporating broader criteria, is recommended for clinical trials. Appropriate definitions of NODAT allow for a better understanding of the incidence of this complication and may result in earlier initiation of therapy with improved long-term outcomes.