Short-term efficacy and safety of sitagliptin treatment in long-term stable renal recipients with new-onset diabetes after transplantation

Abstract

New-onset diabetes after transplantation (NODAT) is a common complication after renal transplantation. There are limited available oral drugs to treat hyperglycaemia in this population owing to reduced renal function, potential interactions with immunosuppressive drugs and adverse effects such as hypoglycaemic events that may increase the cardiovascular risk. This study was initiated to investigate efficacy and safety of sitagliptin treatment that may represent a novel alternative in renal transplant recipients. Nineteen long-term stable renal transplant recipients with NODAT were included in a controlled, cross-over study and randomized to first receive either sitagliptin 50-100 mg/day or a sitagliptin-free period of 4 weeks. Median age (interquartile range, IQR) was 67 (62-72) years (12 males/7 females), all studied 1 (1-3) year after transplantation. The immunosuppressive regimen was a triple calcineurin inhibitor-based therapy. Oral glucose tolerance test (OGTT) with insulin and C-peptide responses and laser Doppler (LD) flowmetry assessment of endothelial function were performed at baseline and after each treatment period. Home measurements of plasma glucose were performed daily during the study. The median (IQR) first- and second-phase insulin secretion responses increased significantly by 56.3% (45.2-112.6%, P = 0.005) and 39.3% (26.5-81.0%, P = 0.006), respectively, following sitagliptin treatment as compared with no sitagliptin treatment. Fasting and 2-h plasma glucose concentrations fell significantly {0.9 mmol/L [0.5-1.7 mmol/L (16.2 mg/dL), P = 0.003] and 2.9 mmol/L [0.5-6.4 mmol/L (52.3 mg/dL), P = 0.004], respectively}, as did also home measurements of plasma glucose. Endothelial function and plasma markers of cardiovascular risk were unaffected. No serious adverse events were observed. Two mild and asymptomatic hypoglycaemic episodes were observed in combination with glipizide. Sitagliptin increases insulin secretion and reduces fasting and postprandial plasma glucose in renal transplant recipients with NODAT. The short-term treatment was well tolerated, and sitagliptin seems safe in this population.