Efficacy of the Once-Daily Tacrolimus Formulation LCPT Compared to the Immediate-Release Formulation in Preventing Early Post-Transplant Diabetes in High-Risk Kidney Transplant Patients: A Randomized, Controlled, Open-Label Pilot Study (EUDRACT: 2017-000718-52)

• Published in: Journal of clinical medicine Vol. 13; no. 24; p. 7802
• Main Authors: Torres, Armando, Rodríguez-Adanero, Concepción, Fernández-Rivera, Constantino, Marrero-Miranda, Domingo, de Bonis-Redondo, Eduardo, Rodríguez-Hernández, Aurelio P., Pérez-Tamajón, Lourdes, González-Rinne, Ana, Álvarez-Sosa, Diego, Álvarez-González, Alejandra, Sanchez-Dorta, Nuria, Pérez-Carreño, Estefanía, Díaz-Martín, Laura, Luis-Lima, Sergio, Rodríguez-Rodríguez, Ana E., Vera González, Antonia María de, Romero-Delgado, Cristina, Calvo-Rodríguez, María, Seijo-Bestilleiro, Rocío, Rodríguez-Jiménez, Consuelo, Prieto López, Manuel Arturo, Rivero-González, Antonio Manuel, Hernández-Marrero, Domingo, Porrini, Esteban
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 20.12.2024; MDPI
• Subjects: Biopsy; Cytomegalovirus; Diabetes; Disease prevention; Dosage and administration; Glucose; High density lipoprotein; Immunology; Insulin resistance; Kidney transplants; Kidneys; Metabolism; Patient outcomes; Patients; Prevention; Risk factors; Steroids; Tacrolimus; Transplantation; Triglycerides; Spain; Madrid Spain; post-transplant diabetes; post-transplant prediabetes; tacrolimus pharmacokinetics; early-release tacrolimus; kidney transplantation; LCPT tacrolimus
• ISSN: 2077-0383; 2077-0383
• DOI: 10.3390/jcm13247802

Background/Objectives: Post-transplant diabetes mellitus (PTDM) and prediabetes (PreDM) are common after renal transplantation and increase the risk of cardiovascular events and mortality. Compared to immediate-release tacrolimus (IR-Tac), the LCPT formulation, with delayed absorption, offers higher bioavailability and a smoother time–concentration curve, potentially reducing beta-cell stress. Methods: This randomized pilot trial compared de novo immunosuppression with IR-Tac (twice daily) and LCPT (once daily). At-risk recipients (age ≥ 60 years or 18–59 years with metabolic syndrome) were enrolled and followed for 3 months. The primary and secondary outcomes were the incidence of PTDM and PreDM, respectively. Results: 27 patients were randomized to IR-Tac and 25 to LCPT. The incidence of PTDM was comparable between groups [IR Tac: 18.5% (95% CI: 8.2–36.7%) vs. LCPT: 24% (95% CI: 11.5–43.4%); p = 0.7]. Although not statistically significant, the LCPT group exhibited a trend toward a reduction in PreDM incidence [IR-Tac: 40.7% (95% CI: 25–59%) vs. LCPT: 20% (95% CI: 9–39%); p = 0.1]. A sensitivity analysis showed similar results, with no significant differences in cumulative corticosteroid doses or baseline body mass index (BMI) between groups. The LCPT group showed a trend toward higher tacrolimus exposure at the end of the study [trough levels: IR-Tac group 8.3 (6.9–9.2) vs. LCPT group 9.4 (7.4–11.4) ng/mL; p = 0.05)], as well as fewer acute rejection episodes (none vs. three). Delayed graft function was more common in the IR-Tac group (37% vs. 8%; p = 0.01), and the eGFR was lower. Adverse events were comparable between groups. Conclusions: The potential biological activity of LCPT in preventing glucose metabolic alterations in at-risk patients warrants further investigation.