An anti-diabetic drug or oral hypoglycemic agent is used to treat diabetes mellitus. The medications usually work by lowering the glucose levels in the blood. There are different types of anti-diabetic drugs, and their use depends on the nature of the diabetes, age and situation of the person, as well as other factors.
Insulin, exenatide, and pramlintide are the only non-oral antidiabetic drugs. Insulin is the mainstay of treatment in Type 1 diabetes, in which insulin production is impaired. In Type 2 diabetes, insulin is used when oral medication has become ineffective. Exenatide and pramlintide are new injectable medications approved in 2005 in the US by the FDA to treat type 2 diabetes.
Sulfonylureas were the first widely used oral hypoglycemic medications. They trigger insulin release by direct action pancreatic Beta cells. Eight types of these pills have been marketed in North America, but not all remain available. The "second-generation" drugs are now more commonly used. They are more effective than first-generation drugs and have fewer side effects.
In type 2 diabetes the production level of insulin decreases, thus making it hard to regulate glucose level and that leads to increase in sugar level in blood which acts as poison. Sulfonylureas are only useful in Type 2 diabetes, as they work by stimulating the release of insulin. They work best with patients over 40 years old, who have had diabetes mellitus for under ten years. They can not be used with type 1 diabetes, or gestational diabetes. The primary side effect is hypoglycemia.
- First-generation agents
- Second-generation agents
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Meglitinides are related to sulfonylureas. The amplification of insulin release is shorter and more intense, and they are taken with meals to boost the insulin response to each meal.
- repaglinide (Prandin) - The max dosage is 16 mg/day. Take this drug 0 to 30 minutes prior before eating a meal. If a meal is skipped, then the medication should also be skipped.
- nateglinide (Starlix) - The max dosage is 360 mg/day, usually 120 mg three times a day (TID). It also follows the same recommendations as repaglinide.
Adverse reactions include weight gain and hypoglycemia.
Biguanides reduce hepatic glucose output and increase uptake of glucose by the periphery, including skeletal muscle. 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.
Metformin should be temporarily discontinued before any radiographic procedure involving intravenous iodinated contrast as patients are at an increased risk of lactic acidosis.
Thiazolidinediones, also known as "glitazones", bind to proteins involved in regulating glucose and fat metabolism. They act as "insulin sensitizers" without increasing insulin production.
- rosiglitazone (Avandia)
- pioglitazone (Actos)
- troglitazone (Rezulin): used in 1990s, withdrawn due to hepatitis and liver damage risk.
Alpha glucosidase inhibitorsEdit
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.
These medications are rarely used in the United States because of the severity of their side effects (flatulence and bloating). They are more commonly prescribed in Europe.
Exenatide (also Exendin-4, marketed as Byetta) is the first of a new class of medications approved for the treatment of type 2 diabetes. It is to be used in conjunction with oral medications such as metformin and/or a sulfonylurea to improve glucose control. The medication is injected twice per day using a specially designed pen. The typical human response is both an improvement of the release of internal insulin by the pancreas and suppression of pancreas glucagon release, behaviors more typical of individuals without blood sugar control problems. In the presence of exenatide, these responses are greater when the blood sugar is elevated.
- Dipeptidyl peptidase-4 (DPP-4) inhibitors (vildagliptin, sitagliptin) increase blood concentration of GLP-1 (glucagon-like peptide-1).
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. Others are undergoing phase I/II studies.
- PPARα/γ ligands (muraglitazar and tesaglitazar) - development stopped due to adverse risk profile
- SGLT (sodium-dependent glucose transporter 1) inhibitors increase urinary glucose.
- FBPase (fructose 1,6-bisphosphatase) inhibitors decrease gluconeogenesis in liver.
Insulin by mouthEdit
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 through the stomach and gut. One alternative delivery method is by inhalation. In 2006, the U.S. Food and Drug Administration approved the use of Exubera, the first inhalable insulin.
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. 
- Lebovitz HE. Therapy for Diabetes Mellitus and Related Disorders. 4th edition. Alexandria: American Diabetes Association, 2004.
- Holland, Norman & Adams, Michael Patrick. Core Concepts in Pharmacology. Pearson Education, Inc. New Jersey. 2003.
Anti-diabetic drug informationEdit
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