Insulin secretion in liver transplant recipients following conversion to a prolonged release tacrolimus formulation

Can Liver J. 2023 Oct 30;6(3):353-357. doi: 10.3138/canlivj-2022-0046. eCollection 2023 Oct.

Abstract

Background: Post liver transplant diabetes mellitus (PLTDM) occurs in 10-40% of liver transplant recipients and is associated with increased morbidity and mortality. An important cause of PLTDM is tacrolimus induced, concentration-dependent, inhibition of insulin secretion.

Objective: To determine if a newly licenced formulation of tacrolimus (Envarsus-PA), which achieves peak tacrolimus concentrations 20-30% lower than other tacrolimus formulations has less of an inhibitory effect on insulin secretion.

Methods: Homeostatic model assessment (HOMA) for insulin secretion (HOMA-S) values and c-peptide levels were determined in 19 adult liver transplant recipients while being maintained on immediate- or slow-release tacrolimus formulations and repeated a minimum of 30 days following conversion to Envarsus-PA.

Results: Insulin secretion was unchanged following conversion to Envarsus-PA (HOMA-S pre-conversion: 154 ± 133 vs. 129 ± 75, post-conversion [p = 0.32], and c-peptide levels; 1059 ± 602 and 934 ± 463 respectively, p = 0.42). Fasting blood glucose (FBG) and hemoglobin A1c (HbA1c) levels were also unchanged (FBG 5.7 ± 0.8 pre-conversion vs. 5.6 ± 0.7 post-conversion; p = 0.36 and HbA1c 4.9±1.2 pre-conversion versus 5.5±0.2 post-conversion, p = 0.34).

Conclusions: Envarsus-PA had no significant effect on insulin secretion or glucose homeostasis beyond that associated with other tacrolimus formulations in adult liver transplant recipients.

Keywords: PA; envarsus; formulations; insulin; secretion; tacrolimus.

Grants and funding

Funding: This research was funded in part by an unrestricted educational grant from Paladin Labs Inc.