The impact of vildagliptin as an add‐on therapy on matrix metalloproteinase‐14 levels, liver stiffness and subclinical atherosclerosis in adolescents with type 1 diabetes and non‐alcoholic steatohepatitis: A randomized controlled trial

Abstract Aim Many patients with type 1 diabetes mellitus (T1DM) met the histological criteria for non‐alcoholic steatohepatitis (NASH), which leads to cardiovascular disease morbidity and mortality. Matrix metalloproteinase‐14 (MMP‐14) is involved in cardiovascular disease and atherosclerosis. Objectives To assess the impact of oral dipeptidyl peptidase‐4 inhibitor, vildagliptin, as adjunctive therapy on NASH in adolescents with T1DM and its effect on glycaemic control, MMP‐14 levels and carotid intima media thickness (CIMT). Methods Sixty adolescents with T1DM and NASH were randomly assigned to receive oral vildagliptin (50 mg once daily) for 6 months or not. Glycated haemoglobin, lipid profile, hepatic steatosis index, triglyceride glucose (TyG) index and MMP‐14 levels were assessed. Transient elastography with controlled attenuation parameter (CAP) was performed together with measuring CIMT. Results By transient elastography, 12 (20%) patients with T1DM with NASH had elevated liver stiffness ≥7 kPa (F2 stage or higher). Baseline MMP‐14 was positively correlated to insulin dose ( p = 0.016), triglycerides and TyG index, CIMT, liver stiffness and CAP levels among the studied patients ( p < 0.001 for all). After 6 months, patients with T1DM on vildagliptin therapy had significantly lower glycated haemoglobin, lipid profile, hepatic steatosis index and TyG index, as well as MMP‐14 ( p < 0.001). CIMT, liver stiffness and CAP were significantly decreased post‐therapy compared with baseline levels and compared with the control group ( p < 0.001). Vildagliptin was safe and well‐tolerated. Conclusions Administration of vildagliptin for adolescents with T1DM and NASH improved glycaemic control, dyslipidaemia and MMP‐14 levels and decreased liver stiffness and CIMT; hence, reducing subclinical atherosclerosis and disease progression.