Oral glucose lowering agents (oral hypoglycemic agents)

Introduction

Oral antidiabetic drugs are used for the treatment of type 2 diabetes mellitus. They should be prescribed only if the patient fails to respond adequately to at least 3 months restriction of energy and carbohydrates intake and an increase in physical activity. They should be used to augment the effect of diet and exercise, and not to replace them.
Advances in the therapy of type 2 DM have generated considerable enthusiasm for oral glucose-lowering agents that target different pathophysiologic processes in type 2 DM. Based on their mechanisms of action, oral glucose-lowering agents are subdivided into agents that;

1. increase insulin secretion,
2. reduce glucose production, or
3. increase insulin sensitivity .

Agents that increase insulin secretion (INSULIN SECRETAGOGUES)

Insulin secretagogues stimulate insulin secretion by interacting with the ATP-sensitive potassium channel on the beta cell. These drugs are most effective in individuals with type 2 DM of relatively recent onset, who tend to be obese and have residual endogenous insulin production. At maximum doses, first-generation sulfonylureas are similar in potency to second-generation agents but have a longer half-life, a greater incidence of hypoglycemia, and more frequent drug interactions. Thus, second-generation sulfonylureas are generally preferred.

Agents that reduce glucose production

Glucosidase inhibitors (acarbose and miglitol) reduce postprandial hyperglycemia by delaying glucose absorption; they do not affect glucose utilization or insulin secretion. Postprandial hyperglycemia, secondary to impaired hepatic and peripheral glucose disposal, contributes significantly to the hyperglycemic state in type 2 DM. These drugs, taken just before each meal, reduce glucose absorption by inhibiting the enzyme that cleaves oligosaccharides into simple sugars in the intestinal lumen. Therapy should be initiated at a low dose.
Metformin is representative of this class of agents. It reduces hepatic glucose production through an undefined mechanism and improves peripheral glucose utilization slightly

Agents that increase insulin sensitivity or reduce resistance

Thiazolidinediones reduce insulin resistance. These drugs bind to the PPAR (peroxisome proliferator-activated receptor) nuclear receptor. The PPAR-_ receptor is found at highest levels in adipocytes but is expressed at lower levels in many other tissues.

Classes of drugs
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1. Sulphonylureas
2. Biguanides
3. Thiazolidinediones (Glitazones)
4. Alpha-Glucosidase inhibitors
5. Meglitinides