An oral hypoglycemic agent is a medication (usually a pill or capsule) that can be take by mouth to lower a high blood sugar toward normal. Oral hypoglycemic agents are most often used in the treatment of diabetes mellitus, especially type 2 diabetes, and are often referred to as "diabetes pills." In many contexts, they are considered an alternative to insulin injections, but generally do not work well in those persons whose pancreases no longer can release insulin, such as those with ordinary type 1 diabetes.

There are several classes of these blood-sugar lowering drugs. The classes vary by mechanism of action, with each class containing a few very similar agents. Most lower glucose by either stimulating insulin release or by increasing or amplfying the effect of the insulin already present. Different classes may offer specific advantages that make them more or less attractive for the varied circumstances of individual patients.

In the following list of "diabetes pills" used in the last few decades, each medication is listed by generic name, with the most common North American brand name in parentheses.

Sulfonylureas

Sulfonylureas were the first widely used oral hypoglycemic medications. They are insulin secretagogues, triggering insulin release by direct action on the K_ATP channel of the pancreatic beta cells. Seven types of these pills have been marketed in North America. Four, known as "first-generation" drugs, have been in use for some time, but not all remain available. Three "second-generation" drugs, are now more commonly used. They are stronger than first-generation drugs and have fewer side effects.

• First-generation agents
  • Tolbutamide (Orinase)
  • Acetohexamide (Dymelor)
  • Tolazamide (Tolinase)
  • Chlorpropamide (Diabinese)
• Second-generation agents
  • Glipizide (Glucotrol)
  • Glyburide (Diabeta, Micronase, Glynase)
  • Glimepiride (Amaryl)

Meglitinides

Meglitinides are related to sulfonylureas. The amplification of insulin release is shorter and more intense, and they are take with meals to boost the insulin response to each meal.

• Repaglinide (Prandin)
• Nateglinide (Starlix)

Biguanides

Biguanides reduce hepatic glucose output. Although it must be used with caution in patients with impaired liver or kidney function, metformin has become the most commonly used agent for type 2 diabetes in children and teenagers.

• Metformin (Glucophage)
• Phenformin (DBI): used in 1960-1980s, withdrawn due to lactic acidosis risk.

Thiazolidinediones

Thiazolidinediones, also known as "'glitazones," bind to PPARγ, a type of nuclear regulatory protein involved in transcription of numerous genes regulating glucose and fat metabolism. They act as "insulin sensitizers" without increasing insulin secretion.

• Rosiglitazone (Avandia)
• Pioglitazone (Actos)
• Troglitazone (Rezulin): used in 1990s, withdrawn due to liver damage risk.

Alpha glucosidase inhibitors

Alpha glucosidase inhibitors are "diabetes pills" but not technically hypoglycemic agents because they do not have a direct effect on insulin secretion or sensitivity. These agents slow the digestion of starch in the small intestine, so that glucose from the starch of a meal enters the bloodstream more slowly, and can be matched more effectively by an impaired insulin response or sensitivity. These agents are effective by themselves only in the earliest stages of impaired glucose tolerance, but can be helpful in combination with other agents in type 2 diabetes.

• Miglitol (Glyset)
• Acarbose (Precose)

Experimental agents

Many other potential drugs are currently in investigation by pharmaceutical companies. Some of these are simply newer members of one of the above classes, but some work by novel mechanisms. For example, at least one compound that enhances the sensitivity of glucokinase to rising glucose is in the stage of animal research.

The ultimate oral hypoglycemic agent: insulin by mouth

The basic appeal of oral hypoglycemic agents is that most people would prefer a pill to an injection. Unlike all the oral drugs described in this article, insulin is a protein. Protein hormones, like meat proteins, are digested in the stomach and gut.

However, the potential market for an oral form of insulin is enormous and many laboratories have attempted to devise ways of moving enough intact insulin from the gut to the portal vein to have a measurable effect on blood sugar. One can find several research reports over the years describing promising approaches or limited success in animals, and limited human testing, but as of 2004, no products appear to be successful enough to bring to market.[1] (http://www.ias.ac.in/resonance/May2003/May2003p38-46.html)

Reference

Lebovitz HE. Therapy for Diabetes Mellitus and Related Disorders. 4th edition. Alexandria:American Diabetes Association, 2004.