Oral Diabetes Agents

Class	Mechanism of Action	Benefits	Risks/Concerns
Sulfonylureas	Bind to sulfonylurea receptor on beta cells, stimulating insulin release; long duration of action	Extensive clinical experience; improved microvascular outcomes in UKPDS; low cost; once-daily dosing possible	Hypoglycemia; weight gain; potential impairment of cardiac ischemic preconditioning
Glyburide Glipizide Glimepiride
Glinides (meglitinides)	Bind to sulfonylurea receptor on beta cells, stimulating insulin release; short duration of action	Target postprandial glucose; mimics physiologic insulin secretion	Hypoglycemia; weight gain; no long-term studies; expensive; frequent dosing (compliance an issue)
Repaglinide Nateglinide
Biguanides	Decrease hepatic glucose production	Extensive clinical experience; no hypoglycemia; weight loss or weight neutral; lipid and other nonglycemic vascular benefits; improved macrovascular outcomes; low cost; once-daily dosing available (sustained-release product)	Diarrhea, abdominal discomfort; many contraindications to consider, including serum creatinine >1.4 mg/dL (123.76 µmol/L) and lactic acidosis risk (rare); lowers vitamin B12 levels (without apparent effects on hematologic indices or neurologic function)
Metformin
α-Glucosidase inhibitors	Retard gut carbohydrate absorption	Target postprandial glucose; weight-neutral; nonsystemic	Flatulence, abdominal discomfort; frequent dosing (compliance); expensive
Acarbose Miglitol
Thiazolidinediones	Activate the nuclear receptor PPARγ, increasing peripheral insulin sensitivity. May also reduce hepatic glucose production	Address primary defect of T2DM; no hypoglycemia; lipid and other nonglycemic vascular benefits; probable decreased macrovascular outcomes with pioglitazone; greater durability of effectiveness; once-daily dosing	Edema and heart failure risk; weight gain; possible increased fracture risk in women; possible increased myocardial infarction risk with rosiglitazone; slow onset of action; expensive
Rosiglitazone Pioglitazone
Amylinomimetics	Activate amylin receptors, decreasing glucagon secretion, delaying gastric emptying, and enhancing satiety	Weight loss	Nausea, vomiting; hypoglycemia risk when used with insulin; no long-term studies; injectable; expensive; frequent dosing (compliance)
Pramlintide
Incretin modulators	Activate GLP-1 receptors, increasing glucose-dependent insulin secretion, decreasing glucagon secretion, delaying gastric emptying, and enhancing satiety	No hypoglycemia; weight loss	Nausea, vomiting; possible pancreatitis (rare); no long-term studies; injectable; expensive
GLP-1 mimetics Exenatide
DPP-IV inhibitors	Inhibit degradation of endogenous GLP-1 and GIP, thereby enhancing the effect of these incretins on insulin and glucagon secretion	No hypoglycemia; weight neutral; once-daily dosing	Possible urticaria/angioedema (rare); no long-term studies; expensive
Sitagliptin
Bile acid sequestrants	Bind cholesterol within bile acid; unknown mechanisms of antihyperglycemic effect	No hypoglycemia; weight neutral; lowers LDL-cholesterol	Constipation; may increase triglycerides; no long-term studies; expensive
Colesevelam

Reference: MKSAP 15
http://mksap15.acponline.org/tables/en_t07