P1029safety and Efficacy of Long-Term Administration of DPP-4 Inhibitors in Patients With New Onset Diabetes After Kidney Transplantation

Abstract

Background and Aims New onset diabetes (NODAT) is a common complication after kidney transplantation. The available treatment options in this patient population have limitations due to reduced renal function, possible interactions with immunosuppressive drugs and side effects such as hypoglycemic events. The aim of this study was to investigate the long term safety and efficacy profile of dipeptidyl peptidase-IV (DDP-4 inhibitors) administration in renal transplant recipients with NODAT. Method The study included 12 patients treated with DPP-IV inhibitors monotherapy as well as 5 patients receiving insulin monotherapy as initial treatment immediately after NODAT diagnosis. All patients were monitored at every scheduled outpatient visit and for 12 months after diagnosis by measuring glycosylated hemoglobin (HbA1c), serum creatinine (eGFR calculation with CKD-EPI formula), plasma immunosuppressive trough levels, serum lipids, blood pressure, and body weight. The mean values of the aforementioned parameters for the last six months of follow up were compared to the ones at diagnosis. Results Patients receiving DPP-IV inhibitors were treated with either linagliptin (4 patients), sitagliptin (4 patients), vildagliptin (2 patients) or halogliptin (2 patients). These patients had a mean age of 59.4 ± 12 years, a mean HbA1c of 6.6% and a mean fasting glucose of 114.5 mg/dl at diagnosis. The mean HbA1c the last 6 months of one year of follow up after initiation of treatment, decreased to 6.1% (p=0.03). Renal function remained stable (mean eGFR from 58.8 to 61.7 ml/min/1.73m2, p=ns) while plasma tacrolimus levels did not appear to be affected (from 6.2 to 5.5 ng/dl, p=ns). Patients received a slightly reduced mean dose of tacrolimus during the last six months of follow up in comparison to the one at initiation of treatment (from 2.9 to 2.6 mg/24h, p=ns). No significant difference was shown in serum total, LDL, and HDL cholesterol before and after treatment, nevertheless, triglyceride levels were significantly reduced (from 214.4 to 174.9 mg/dl, p=0.0039). A decrease in body weight was observed (from 79.9 to 77.9 kg, p=ns) which was however not statistically significant. Finally, achieving the goal of lowering HbA1c levels was better in patients treated with DPP-IV inhibitors than in those treated with insulin (6.1% vs 7.1%, respectively, p=0.01). Conclusion Administration of DPP-IV inhibitors appears to be a safe and effective option for the treatment of NODAT in renal transplant recipients with the benefit of avoiding hypoglycemic episodes and possibly better diabetes control than with insulin therapy.