COMPARISON OF THE REDUCTION of INSULIN RESISTANCE BY TADALAFIL AND DAPAGLIFLOZIN AS A COMBINATION THERAPY OVER DAPAGLIFLOZIN MONOTHERAPY IN DIABETIC NAFLD PATIENT :A RANDOMISED CONTROL TRIAL

Non-alcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease, affecting approximately one-quarter of the global population, and has become a world public health issue. NAFLD is a clinicopathological syndrome characterized by hepatic steatosis, excluding ethanol and other definite liver damage factors. Recent studies have shown that the development of NAFLD is associated with lipid accumulation, oxidative stress, endoplasmic reticulum stress, and lipotoxicity.

Phosphodiesterase-5 (PDE-5) inhibitors are drugs targeting endothelial dysfunction through increased NO-signalling, resulting in relaxation of vascular smooth muscles and vasodilation.This drug class is currently used in the clinic for the treatment of erectile dysfunction, pulmonary hypertension, and lower urinary tract symptoms. studies have also suggested cardio protective effects.Several preclinical and clinical studies have also demonstrated beneficial metabolic effects of PDE-5 inhibitors for manifestations of the metabolic syndrome and also reduce ALT which is a fatty liver marker

Dapagliflozin treatment remarkably suppressed oleic acid (OA)-induced lipid accumulation and TG content in L02 cells through increased FA β-oxidation, as indicated by elevated proliferator-activated receptor-gamma coactivator-1 alpha (PGC-1α) levels and activation of the AMP-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) signaling pathway