Table 3. Mechanisms of action of current antidiabetic agents on non‐alcoholic fatty liver disease.
Class of antidiabetic agent | Example | Primary mechanism | Effects on liver or adipose tissue hormone expression | Actions in NAFLD | Reference |
---|---|---|---|---|---|
Biguanides | Metformin | Activates AMPK | Induces FGF21 expression in hepatocytes |
Improves insulin resistance Reduces aminotransferase levels Reduces hepatic glucose production Stimulates fatty acid oxidation in liver |
91 |
Thiazolidinediones | Pioglitazone | Activates nuclear transcription factor PPAR‐γ |
Increases circulating adiponectin level Induces FGF21 expression in adipocytes |
Reduces aminotransferase levels Reduces hepatic steatosis, inflammation and fibrosis Improves hepatic insulin sensitivity |
96 |
DPP‐4 Inhibitors | Sitagliptin, vildaglitin, linagliptin, saxagliptin | Inhibits DPP‐4 activity, increasing postprandial GLP‐1 concentrations |
Improves liver enzyme levels and hepatocyte ballooning Reduces plasma glucose and liver enzyme levels |
102 | |
GLP‐1 Receptor Agonists | Exenatide, liraglutide | Activates AMPK in hepatocytes | Increases hepatic FGF21 expression and plasma FGF21 level |
Reduces hepatic lipogenesis Reduces diet‐induced hepatic pro‐inflammatory response Improves insulin sensitivity |
100 |
AMPK, adenosine monophosphate‐activated protein kinase; CAP, Cbl/c‐Cbl‐associated protein; DPP‐4, dipeptidyl peptidase‐4; FGF‐21, fibroblast growth factor‐21; GLP‐1, Glucagon‐like peptide‐1; GLUT‐4, glucose transporter 4; NAFLD, non‐alcoholic fatty liver disease; NASH, non‐alcoholic steatohepatitis; PPAR‐γ, peroxisome proliferator‐activated receptor‐gamma.