Current Advances in the Biochemical and Physiological Aspects of the Treatment of Type 2 Diabetes Mellitus with Thiazolidinediones

Table 1

Class of drugs used for the treatment of type 2 diabetes mellitus.

Class	Compounds	Mechanism	Physiological action	Advantages	Disadvantages
Biguanides	Metformin	Activates AMP kinase	hepatic glucose production	Low cost, no weight gain, no hypoglycemia,; CVD events	Gastrointestinal side effects, lactic acidosis, vitamin B12 deficiency
Sulfonylureas	Glyburide Glibenclamide Glipizide Glimepiride	Closes K-ATP channels on β cell plasma membranes	↑ insulin secretion	Low cost,; microvascular risk	Hypoglycemia, weight gain
Meglitinides	Repaglinide; Nateglinide	Closes K-ATP channels on β cell plasma membranes	↑ insulin secretion	postprandial glucose	High cost, hypoglycemia, weight gain, frequent dosing
α-Glucosidase inhibitors	Acarbose Miglitol	Inhibits intestinal α-glucosidase	Slows intestinal carbohydrate digestion/absorption	Moderate cost, no hypoglycemia,; postprandial glucose; CVD events	Modest HbA1c efficacy, gastrointestinal side effects, frequent dosing
DPP4 inhibitors	Sitagliptin Vildagliptin Saxagliptin Linagliptin	Inhibits DPP4 activity, increasing postprandial incretin GLP-1 concentration	insulin secretion; glucagon secretion	No hypoglycemia	High cost, modest HbA1c efficacy, angioedema, pancreatitis
GLP-1 receptor agonists	Exenatide; Liraglutide	Activates GLP-1 receptors	insulin secretion; glucagon secretion; satiety; slows gastric emptying	No hypoglycemia, weight loss	High cost, gastrointestinal side effects, acute pancreatitis
Bile acid sequestrants	Colesevelam	Binds bile acids in intestinal tract, increasing hepatic bile acid production	hepatic glucose production; incretin levels	No hypoglycemia; LDL	High cost, modest HbA1c efficacy, constipation; triglycerides
Dopamine 2 agonists	Bromocriptine	Activates dopaminergic receptors	Modulates hypothalamic regulation of metabolism; insulin sensitivity	No hypoglycemia; CVD events	High cost, modest HbA1c efficacy, dizziness, syncope, nausea, fatigue
Thiazolidinediones	Pioglitazone; Rosiglitazone	Activates the nuclear transcription factor PPARγ	insulin sensitivity	No hypoglycemia; HDL; triglycerides; CVD events	High cost, weight gain, edema/heart failure, bone fractures, bladder cancer (pioglitazone); ↑ LDL
Insulin	Human NPH; Human regular; Lispro; Aspart; Glulisine; Glargine; Detemir; Premixed	Activates insulin receptors	glucose disposal; hepatic glucose production	Universally effective; microvascular risk	Variable cost, hypoglycemia, weight gain