Onset and progression of diabetes in kidney transplant patients receiving everolimus or cyclosporine therapy: an analysis of two randomized, multicenter trials.
Sommerer C, Witzke O, et al.BMC Nephrology, 2018; 19(1): 237.
Aims
A post hoc analysis of two trials (ZEUS; HERAKLES) to compare the incidence and severity of posttransplant diabetes mellitus (PTDM) and progression of pre-existing diabetes post-transplant in patients receiving everolimus-based CNI-free maintenance immunosuppression versus standard CsA-based regimen or everolimus with reduced-exposure CsA.
Interventions
In both studies (ZEUS and HERAKLES), patients received standard-exposure CsA with enteric-coated mycophenolate sodium (EC-MPS) and steroids from time of transplant. They were randomized to continue the CsA-based regimen or convert to everolimus at 4.5 months (ZEUS) or 3 months (HERAKLES) post-transplant. There was a third treatment arm in the HERAKLES study in which patients received everolimus with reduced-exposure CsA.
Participants
De novo kidney transplant recipients from the ZEUS (n=300) and HERAKLES (n=497) studies.
Outcomes
Outcomes compared between treatment groups up to Month 12 post-transplant within the ZEUS and HERAKLES trials were the incidence of PTDM; requirement for hypoglycemic therapy (insulin or non-insulin); change in random blood glucose; estimated GFR (eGFR) at Month 12 and the change in eGFR from randomization to Month 12.
Follow-up
12 months
CET Conclusions
This post-hoc, pooled analysis of the ZEUS and HERAKLES trials compared the incidence and severity of posttransplant diabetes mellitus (PTDM) and progression of pre-existing diabetes in patients receiving everolimus versus patients on CsA-based regimens or everolimus plus reduced CsA. In both trials patients received standard CsA plus enteric-coated mycophenolate sodium and steroids and were converted at 3 months (HERAKLES) or 4.5 months (ZEUS) to everolimus. Analyses were done for the safety populations which consisted of all patients receiving at least one dose of the study drug. There was no difference in the incidence of PTDM for patients in the everolimus groups versus CsA groups in either trial or when data from both trials were pooled. There was also no difference in progression of random glucose concentrations between groups in patients with pre-existing diabetes. The authors conclude that there are no differences in the incidence or severity of PTDM in patients converted from CsA to everolimus.
Data analysis
Modified intention-to-treat analysis
Trial registration
ClinicalTrials.gov - NCT00154310 and NCT00514514; EudraCT - 2006-007021-32 and 2004-004346-40.