Metabolic Sequelae of Everolimus Treatment After Cardiac Transplant: A Hypothesis-Generating Study

Heart Lung Circ. 2023 Sep;32(9):1076-1079. doi: 10.1016/j.hlc.2023.05.014. Epub 2023 Jun 22.

Abstract

Background: Although modern immunosuppressants improve survival post-transplant, they are associated with long-term metabolic complications, such as post-transplant diabetes mellitus (PTDM). Calcineurin inhibitor-sparing regimens using everolimus attenuate some complications such as left ventricular hypertrophy. However, the metabolic effects of everolimus following transplant are less clear.

Methods: Post-hoc analysis to compare PTDM and other metabolic outcomes in participants of a randomised open-label clinical trial of low-dose everolimus and tacrolimus versus standard-dose tacrolimus in heart transplant recipients (RADTAC1 study).

Results: There were 39 participants in the trial; mean follow-up was 6.4±1.5 years. There was a high rate of pre-existing diabetes (26%) and newly diagnosed PTDM (36%) during follow-up. Half the patients who developed PTDM in the everolimus-tacrolimus group (n=4/8) ceased diabetes medications during follow-up, which was not observed in patients on standard tacrolimus (n=0/6). In the first 12 months there was a higher use of non-insulin treatment for diabetes in the everolimus-tacrolimus group compared to the standard tacrolimus group.

Conclusions: This study suggests that treatment with everolimus may be associated with improved glycaemic control of PTDM relative to treatment with standard doses of calcineurin inhibitor. These findings should be further studied in prospective randomised trials.

Keywords: Calcineurin inhibitor; Diabetes; Everolimus; Heart transplant; Post-transplant diabetes.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Calcineurin Inhibitors / adverse effects
  • Diabetes Mellitus*
  • Disease Progression
  • Everolimus
  • Graft Rejection
  • Heart Transplantation*
  • Humans
  • Prospective Studies
  • Tacrolimus / therapeutic use

Substances

  • Everolimus
  • Tacrolimus
  • Calcineurin Inhibitors