ORAL HYPOGLYCEMIC AGENTS (OHAs) SULFONYLUREAS

SULFONYLUREAS

Sulfonylureas work primarily by stimulating pancreatic insulin secretion, which in turn reduces hepatic glucose output and increases peripheral glucose disposal.
The sulfonylureas are often classified as belonging to the first or second generation.

The First generation sulfonylureas:

* Acetohexamide
* Chlorpropamide
* Tolazamide
* Tolbutamide.

The Second generation sulfonylureas :

* Glibenclamide
* Glyburide
* Glipizide
* Glicazide
* Glimepiride

The first generation sulfonylureas are rarely used now.

BIGUANIDES

Two drugs in this category are phenformin and metformin.

Biguanides work mainly by

* Suppressing excessive hepatic glucose production
* Increasing glucose utilization in peripheral tissues to a lesser degree.
* Possibly reduce food intake and thus reduce intestinal glucose absorption

As the biguanides do not stimulate endogenous insulin secretion, hypoglycemia does not occur when they are used alone and therefore they are sometimes called anti-hyperglycemic agents rather hypoglycemic agents.

The use of phenformin has decreased considerably and it is usually metformin that is now used when a biguanide is prescribed.

ALPHA-GLUCOSIDASE INHIBITORS

Acarbose is an alpha-glucosidase inhibitor that slows down the breakdown of disaccharides and polysaccharides and other complex carbohydrates into monosaccharides. The enzymatic generation and subsequent absorption of glucose is delayed and the postfood blood glucose values, which are characteristically high in patients with type II diabetes, are reduced.

MEGLITINIDES

A very recent addition to the OHA group. It is a ultra short acting drug which acts directly on the the beta cells of the pancreas and increases the secretion of insulin. It also corrects the problems with the pulsatile release of insulin which is seen in Type II diabetes.

THIAZOLINEDIONES

Thiazolidinediones are a new class of oral antidiabetic agents (commercially known as glitazones) that enhance insulin sensitivity in peripheral tissues. Troglitazone was the first glitazone introduced to the market, and though widely used, it has now been withdrawn from the market as its use has been linked with hepatocellular injury and death secondary to liver failure.

Rosiglitazone and Pioglitazone are now available for clinical use and are extremely potent in reducing peripheral insulin resistance.