Effect of Dipeptidyl Peptidase-4 Inhibitors Supplementation on Non-Alcoholic Steatohepatitis in Adolescents with Type 1 Diabetes Mellitus

Abstract Background Many patients with type 1 diabetes mellitus (T1DM) had histological evidence of steatosis and met the histological criteria for non-alcoholic steatohepatitis (NASH). Accumulating data suggested that dipeptidyl peptidase-4 (DDP-4) enzyme is involved in the development of various chronic liver diseases. Some studies showed the beneficial effect of DDP-4 inhibitors in liver injury for their ability in modulating fatty acid oxidation, decreasing lipogenesis and improving hepatic glucose metabolism. Objectives Therefore, we performed a randomized-controlled trial to assess the effect of the oral DPP- 4 inhibitor vildagliptin as an add-on therapy on NASH in adolescents with T1DM as well as its effect on glycemic control, lipid profile. Methods This study included 60 adolescents with T1DM and NASH. Patients were randomly assigned into two groups; intervention group who received oral vildagliptin (50 mg daily). The other group did not receive any supplementation and served as a control group. Both groups were followed- up for six months with assessment of fasting and 2 hours post-prandial blood glucose levels, HbA1c, liver function tests, fasting lipid profile and hepatic steatosis index. Results Supplementation with oral DPP-4 inhibitor vildagliptin was safe and well-tolerated. After six months, Vildagliptin adjuvant therapy for the intervention group resulted in a significant decrease of systolic and diastolic blood pressure as well as insulin dose (p < 0.001). Blood glucose levels, HbA1c, liver enzymes, triglycerides, total cholesterol and hepatic steatosis index were significantly lower after vildagliptin therapy compared with baseline levels and compared with the control group (p < 0.001). Conclusions The DDP-4 inhibitor vildagliptin in a once daily dose of 50 mg orally for six months as an add-on therapy for adolescents with T1DM and NASH was safe and improved glycemic control and dyslipidemia while decreasing steatosis; hence, preventing disease progression.