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.