Treatment
Table 1. Properties Of Currently Available Glucose-Lowering Agents that may Guide Treatment Choice in Individual Patients With T2DM
Class Biguanides
Compound(s) • Metformin
Cellular Mechanism
Activates AMP-kinase
Primary Physiological Action(s)
• ↓ Hepatic glucose production
Sulfonylureas
• 2nd generation • Glyburide/ glibenclamide
• Glipizide • Glimepiride
Meglitinides (glinides)
• Repaglinide • Nateglinide
Thiazolidinediones • Pioglitazone • Rosiglitazoneb
Closes KATP channels on β-cell plasma membranes
Closes KATP channels on β-cell plasma membranes
Activates the nuclear transcription factor PPAR-γ
• ↑ Insulin secretion
• ↑ Insulin secretion
• ↑ Insulin sensitivity
α-Glucosidase inhibitorsa
• Acarbose • Miglitol
Inhibits intestinal α-glucosidase
• Slows intestinal carbohydrate digestion/ absorption
DPP-4 inhibitors
• Sitagliptin • Vildagliptina • Saxagliptin • Linagliptin
Bile acid sequestrantsa
• Colesevelam
Inhibits DPP-4 activity, increasing postprandial active incretin (GLP-1, GIP) concentrations
Binds bile acids in intestinal tract, increasing hepatic bile acid production; ? activation of farnesoid X receptor (FXR) in liver
8
• ↑ Insulin secretion (glucose- dependent)
• ↓ Glucagon secretion (glucose- dependent)
• Unknown • ? ↓ Hepatic glucose production
• ? ↑ Incretin levels
