Prospective randomized study of conversion from tacrolimus to cyclosporine A to improve glucose metabolism in patients with posttransplant diabetes mellitus after renal transplantation

Am J Transplant. 2018 Jul;18(7):1726-1734. doi: 10.1111/ajt.14665. Epub 2018 Feb 22.

Abstract

Tacrolimus (TAC) increases the risk of posttransplant diabetes (PTDM) compared with cyclosporine A (CYC). The present 12-month, multicenter, investigator-driven, prospective, randomized study was designed to assess whether conversion from tacrolimus to CYC can reverse PTDM after renal transplantation. Predominantly white patients with PTDM according to the 2005 American Diabetes Association criteria were randomized to either replacement of TAC with CYC or continuation of their TAC-based regimen after stratification for type of glucose-lowering therapy, steroid therapy, and hepatitis C status. At 12 months, 14 of 41 patients with complete data in the CYC arm (34%; 95%CI 19%-49%) were free of diabetes, whereas this was the case in only 4 of 39 patients (10%; 95%CI 3%-20%) in the TAC arm (P = .01). At 12 months, 39% of patients in the CYC arm were off glucose-lowering medication vs 13% of patients in the TAC arm (P = .01). The CYC group decreased glycated hemoglobin level during the 12-month follow-up, resulting in significantly lower levels compared with the TAC group (6.0 ± 0.9% vs 7.1 ± 1.7% at 12 months; P = .002). In conclusion, replacement of TAC with CYC significantly improves glucose metabolism and has the potential to reverse diabetes during the first year after conversion. (EU Clinical Trials Register No. 2006-001765-42).

Keywords: clinical research/practice; diabetes: new onset/posttransplant; endocrinology/diabetology; immunosuppressant - calcineurin inhibitor: cyclosporine A (CsA); immunosuppressant - calcineurin inhibitor: tacrolimus; immunosuppression/immune modulation; kidney transplantation/nephrology; rejection: acute.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cyclosporine / therapeutic use*
  • Diabetes Mellitus / drug therapy*
  • Diabetes Mellitus / etiology
  • Diabetes Mellitus / pathology
  • Female
  • Follow-Up Studies
  • Glomerular Filtration Rate
  • Glucose / metabolism*
  • Graft Rejection / drug therapy*
  • Graft Rejection / etiology
  • Graft Rejection / pathology
  • Graft Survival
  • Humans
  • Immunosuppressive Agents / therapeutic use
  • Kidney Failure, Chronic / surgery*
  • Kidney Function Tests
  • Kidney Transplantation / adverse effects*
  • Male
  • Middle Aged
  • Postoperative Complications
  • Prognosis
  • Prospective Studies
  • Risk Factors
  • Tacrolimus / therapeutic use*

Substances

  • Immunosuppressive Agents
  • Cyclosporine
  • Glucose
  • Tacrolimus