Table 3.

Targets and mechanisms of hypoglycemic agents

Medicines	Target organs	Action target	Mechanisms of hypoglycemia
Metformin	Liver, muscle adipose	Modulate mitochondrial enzymes and hepatic redox state, and increases cellular AMP kinase	↓hepatic gluconeogenesis; ↑glucose uptake
SUs	Pancreatic islet β cell	Bind to SUR-1 subunit of the K-ATP channels, leading to channel closure and membrane depolarization	↑insulin secretion
Meglitinides or glinides	Pancreatic islet β cell	Bind to SUR-1 subunit of the K-ATP channels, leading to channel closure and membrane depolarization	↑insulin secretion
AGI	Intestine	Inhibit α-glucosidase in the small intestinal brush border	↓absorption of complex polysaccharide
TZD	Muscle, adipose	Activate PPAR-γ to increase adiponectin and GLUT-4 expression while inhibiting TNF-α effect in adipocytes	↑fatty acid uptake and storage; ↓fat accumulation in the liver, muscle, and pancreas; ↑glucose uptake
DPP-4i	Pancreatic islet α/β cell	Block degradation of incretin hormones (GLP-1 and GIP) by the enzyme DPP-4 and increase incretin hormones levels	↑insulin secretion; ↓glucagon secretion
GLP-1	Pancreatic islet α/β cell	Resistant DPP-4 to extend the half-life of GLP-1 simulate GLP-1 receptor along with “supra-physiologic” GLP-1 levels	↑insulin secretion; ↓glucagon secretion
SGLT-is	Kidney, intestine	Block SGLT-1 in intestine or/and SGLT-2 in kidney receptors and lower the renal threshold for glycosuria	↓intestinal or/and renal glucose reabsorption

SUs Sulfonylureas, SUR-1 sulfonylurea receptor 1, K-ATP ATP sensitive potassium, AGI α-glucosidase inhibitors, TZD thiazolidinediones, PPAR-γ peroxisome proliferator-activated receptor-γ, GLUT-4 glucose transporter type 4, TNF-α tumor necrosis factor, DPP-4i dipeptidyl peptidase-4 inhibitors, GIP glucose-dependent insulinotropic polypeptide, GLP-1 glucagon-like peptide-1, SGLT-is sodium-glucose cotransporter inhibitors