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Oral hypoglycemic agents
Written by Jeffrey R. Waggoner, MD   

Oral hypoglycemic agents are drugs used to treat diabetes (typically Type 2 diabetes). They are taken by mouth (oral) and lower blood sugar (hypoglycemic agents).

There are a number of classes of oral hypoglycemics (OH). Their methods of actions vary, and it is this variation that allows synergistic combination therapy. Staged treatment demands familiarity with these classes and their characteristics. 

Biguanides

Originally derived from Galega (French lilly) extracts, this class of OH has been used since the early 20th century. Their exact mechanism of action has not been defined but probably involves an inhibition of hepatic gluconeogenesis and enhancement of peripheral insulin action by promoting its cellular absorption.

Metformin

Metformin (Glucophage) — This medication is considered the first line drug of choice for type II diabetics, particularly in patients with normal renal function and those who are obese. It is the most prescribed OH. Its primary adverse effect is lactic acidosis.

Sulfonylureas

The first OH used in America, introduced in 1955. Primary action is through stimulation of beta cells to produce more insulin. These medications obviously require some beta cell activity and are thus completely ineffective in patients with Type 1 diabetes or type 2 diabetics whose beta cell activity is substantially diminished.

Tolbutamide, tolazamide, chlorpromamide

Tolbutamide (Orinase), tolazamide (Tolinase), and chlorpromamide (Diabinese) are all first generation sulfonylureas. Their use has been substantially curtailed because they bind to proteins and may be dislodged by other medications. Once freed from protein binding, they can cause significant hypoglycemia.

Glipzide, glyburide, glimepiride

Glipzide (Glucotrol) and glyburide (Micronase, Diabeta, and Glynase) are second generation medications. Glimepiride (Amaryl) is third generation. Because they are not protein bound, their actions and tendency to produce hypoglycemia are less than the first generation. Glynase and Glucotrol XL are long acting. Glimepiride may also promote reduction in insulin resistance. It is also safer in patients with renal disease. [1]

Thiazolidinediones

This class of OH probably works by decreasing peripheral insulin resistance.

Pioglitazone, roziglitazone

Pioglitazone (Actos)—This OH has an additional advantage in that it increases HDL and reduces triglycerides. Roziglitazone (Avandia) increases HDL but also increases LDL to some degree. Roziglitazone and Metformin are combined in Avandamet. [2]

Meglitinide analogues

This class of OH has a rapid onset and short duration that promotes early insulin release. It is thus effective in treating mealtime glucose levations.

Nateglinide,repaglinide

Nateglinide (Starlix) and repaglinide (Pranidin) are members of this class of OH. There have been some studies suggesting that when used as monotherapy, repaglinide is more effective than nateglinide. [3]

Glucosidase inhibitors

These OH work by inhibiting the absorption of carbohydrates. They appear to have no effect on lipids.

Acarbose, miglitol

Acarbose (Presose) and Miglitol (Glyset) are both in this class. [4]

Incretin mimetics

This is the newest class of OH. Its mechanism is an activity that is similar to hormone glucagon-like peptide-1 (GLP-1). This hormone is released from the gut in the presence of food. It then binds to receptors on the beta cells of the pancreas, engendering a release of insulin. It was originally derived from the saliva of the Gila monster.

Exenatide

Exenatide (Byetta) is at present the only medication in this class. In the U.S. it has been cleared for patients already on metformin or a sulfonylurea and not controlled. Initial reports have also suggested that it may aid in weight loss. [5]

 
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