Antidiabetic Drugs


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Antidiabetic Drugs

 

Definition

Antidiabetic drugs are medicines that help control blood sugar levels in people with diabetes mellitus (sugar diabetes).

Purpose

Diabetes may be divided into type I and type II, formerly termed juvenile onset or insulin-dependent, and maturity onset or non insulin-dependent. Type I is caused by a deficiency of insulin production, while type II is characterized by insulin resistance.
Treatment of type I diabetes is limited to insulin replacement, while type II diabetes is treatable by a number of therapeutic approaches. Many cases of insulin resistance are asymptomatic due to normal increases in insulin secretion, and others may be controlled by diet and exercise. Drug therapy may be directed toward increasing insulin secretion, increasing insulin sensitivity, or increasing insulin penetration of the cells.

Description

Antidiabetic drugs may be subdivided into six groups: insulin, sufonylureas, alpha-glucosidase inhibitors, biguanides, meglitinides, and thiazolidinediones.

Key terms

Blood sugar — The concentration of glucose in the blood.
Glucose — A simple sugar that serves as the body's main source of energy.
Hormone — A substance that is produced in one part of the body, then travels through the bloodstream to another part of the body where it has its effect.
Metabolism — All the physical and chemical changes that occur in cells to allow growth and maintain body functions. These include processes that break down substances to yield energy and processes that build up other substances necessary for life.
Pregnancy category — A system of classifying drugs according to their established risks for use during pregnancy. Category A: Controlled human studies have demonstrated no fetal risk. Category B: Animal studies indicate no fetal risk, but no human studies; or adverse effects in animals, but not in well-controlled human studies. Category C: No adequate human or animal studies; or adverse fetal effects in animal studies, but no available human data. Category D: Evidence of fetal risk, but benefits outweigh risks. Category X: Evidence of fetal risk. Risks outweigh any benefits.
Salicylates — A group of drugs that includes aspirin and related compounds. Salicylates are used to relieve pain, reduce inflammation, and lower fever.
Seizure — A sudden attack, spasm, or convulsion.
Insulin (Humulin, Novolin) is the hormone responsible for glucose utilization. It is effective in both types of diabetes, since, even in insulin resistance, some sensitivity remains and the condition can be treated with larger doses of insulin. Most insulins are now produced by recombinant DNA techniques, and are chemically identical to natural human insulin. Isophane insulin suspension, insulin zinc suspension, and other formulations are intended to extend the duration of insulin action, and permit glucose control over longer periods of time. In 2003, research suggested that inhaled forms of insulin offered advantages to injected types, but further study was needed on its long-term effects on the lungs and cost-effectiveness.
Sulfonylureas (chlorpropamide [Diabinese], tolazamide [Tolinase], glipizide [Glucotrol] and others) act by increasing insulin release from the beta cells of the pancrease. Glimepiride (Amaryl), a member of this class, appears to have a useful secondary action in increasing insulin sensitivity in peripheral cells.
Alpha-glucosidase inhibitors (acarbose [Precose], miglitol [Glyset]) do not enhance insulin secretion. Rather, they inhibit the conversion of disaccharides and complex carbohydrates to glucose. This mechanism does not prevent conversion, but only delays it, reducing the peak blood glucose levels. Alpha-glucosidase inhibitors are useful for either monotherapy or in combination therapy with sulfonylureas or other hypoglycemic agents.
Metformin (Glucophage) is the only available member of the biguanide class. Metformin decreases hepatic (liver) glucose production, decreases intestinal absorption of glucose and increases peripheral glucose uptake and use. Metformin may be used as monotherapy (alone), or in combination therapy with a sulfonylurea.
There are two members of the meglitinide class: repaglinide (Prandin) and nateglitinide (Starlix). The mechanism of action of the meglitinides is to stimulate insulin production. This activity is both dose dependent and dependent on the presence of glucose, so that the drugs have reduced effectiveness in the presence of low blood glucose levels. The meglitinides may be used alone, or in combination with metformin. The manufacturer warns that nateglitinide should not be used in combination with other drugs that enhance insulin secretion.
Rosiglitazone (Avandia) and pioglitazone (Actos) are members of the thiazolidinedione class. They act by both reducing glucose production in the liver, and increasing insulin dependent glucose uptake in muscle cells. They do not increase insulin production. These drugs may be used in combination with metformin or a sulfonylurea.

Recommended dosage

Dosage must be highly individualized for all antidiabetic agents and is based on blood glucose levels which must be taken regularly. Patients should review specific literature that comes with antidiabetic medications for complete dosage information.

Precautions

Insulin. The greatest short term risk of insulin is hypoglycemia, which may be the result of either a direct overdose or an imbalance between insulin injection and level of exercise and diet. This also may occur in the presence of other conditions which reduce the glucose load, such as illness with vomiting and diarrhea. Treatment is with glucose in the form of glucose tablets or liquid, although severe cases may require intravenous therapy. Allergic reactions and skin reactions also may occur. Insulin is classified as category B in pregnancy, and is considered the drug of choice for glucose control during pregnancy. Insulin glargine (Lantus), an insulin analog which is suitable for once-daily dosing, is classified as category C, because there have been reported changes in the hearts of newborns in animal studies of this drug. The reports are essentially anecdotal, and no cause and effect relationship has been determined. Insulin is not recommended during breast feeding because either low or high doses of insulin may inhibit milk production. Insulin administered orally is destroyed in the GI tract, and represents no risk to the newborn.
Sulonylureas. All sulfonylurea drugs may cause hypoglycemia. Most patients become resistant to these drugs over time, and may require either dose adjustments or a switch to insulin. The list of adverse reactions is extensive, and includes central nervous system problems and skin reactions, among others. Hematologic reactions, although rare, may be severe and include aplastic anemia and hemolytic anemia. The administration of oral hypoglycemic drugs has been associated with increased cardiovascular mortality as compared with treatment with diet alone or diet plus insulin. The sulfonylureas are classified as category C during pregnancy, based on animal studies, although glyburide has not shown any harm to the fetus and is classified as category B. Because there may be significant alterations in blood glucose levels during pregnancy, it is recommended that patients be switched to insulin. These drugs have not been fully studied during breast feeding, but it is recommended that because their presence in breast milk might cause hypoglycemia in the newborn, breast feeding be avoided while taking sulfonylureas.
Alpha-glucosidase inhibitors are generally well tolerated, and do not cause hypoglycemia. The most common adverse effects are gastrointestinal problems, including flatulence, diarrhea, and abdominal pain. These drugs are classified as category B in pregnancy. Although there is no evidence that the drugs are harmful to the fetus, it is important that rigid blood glucose control be maintained during pregnancy, and pregnant women should be switched to insulin. Alphaglucosidase inhibitors may be excreted in small amounts in breast milk, and it is recommended that the drugs not be administered to nursing mothers.
Metformin causes gastrointestinal (stomach and digestive) reactions in about a third of patients. A rare, but very serious, reaction to metformin is lactic acidosis, which is fatal in about 50% of cases. Lactic acidosis occurs in patients with multiple medical problems, including renal (kidney-related) insufficiency. The risk may be reduced with careful renal monitoring, and careful dose adjustments to metformin. Metformin is category B during pregnancy. There have been no carefully controlled studies of the drug during pregnancy, but there is no evidence of fetal harm from animal studies. It is important that rigid blood glucose control be maintained during pregnancy, and pregnant women should be switched to insulin. Animal studies show that metformin is excreted in milk. It is recommended that metformin not be administered to nursing mothers.
Meglitinides. These drugs are generally well tolerated, with an adverse event profile similar to placebo. The drugs are classified as category C during pregnancy, based on fetal abnormalities in rabbits given about 40 times the normal human dose. It is important that rigid blood glucose control be maintained during pregnancy, and pregnant women should be switched to insulin. It is not known whether the meglitinides are excreted in human milk, but it is recommended that these drugs not be given to nursing mothers.
Thiazolidinediones. These drugs were generally well tolerated in early trials, but they are structurally related to an earlier drug, troglitazone, which was associated with liver function problems. However, in 2003, researchers reported that these drugs, which are used by more than 6 million Americans, may lead to serious side effects. Research showed that after one to 16 months of therapy with pioglitazone or rosiglitazone, some patients developed serious edema and signs of congestive heart failure. Additional studies were underway in late 2003 to determine how these drugs caused fluid build-up and if the symptoms occurred more frequently in certain age groups. The mean age of patients in the 2003 study was 69 years.
It is strongly recommended that all patients treated with pioglitazone or rosiglitazone have regular liver function monitoring. The drugs are classified as pregnancy category C, based on evidence of inhibition of fetal growth in rats given more than four times the normal human dose. It is important that rigid blood glucose control be maintained during pregnancy, and pregnant women should be switched to insulin. It is not known whether the thiazolidinediones are excreted in human milk, however they have been identified in the milk of lactating rats. It is recommended that these drugs not be administered to nursing mothers.

Interactions

The sulfonylureas have a particularly long list of drug interactions, several of which may be severe. Patients should review specific literature for these drugs.
The actions of oral hypoglycemic agents may be strengthened by highly protein bound drugs, including NSAIDs, salicylates, sulfonamides, chloramphenicol, coumarins, probenecid, MAOIs, and beta blockers.
The literature that accompanies each medication should list possible drug-drug or food-drug interactions.

Resources

Periodicals

"Inhaled Insulin Means Better Quality of Life." Health & Medicine Week (September 16, 2003): 189.
"Two Common Diabetes Drugs May Cause Heart Failure and Fluid Buildup." Cardiovascular Week (September 29, 2003): 26.

Organizations

American Diabetes Association. ADA National Service Center, 1660 Duke Street, Alexandria, VA 22314. (800)232-3472. http://www.diabetes.org.
National Diabetes Information Clearinghouse. 1 Information Way, Bethesda, MD 20892-3560. (301)654-3327. ndic@info.niddk.nih.gov.

Other

National Institute of Diabetes and Digestive and Kidney Diseases. http://www.niddk.nih.gov.
References in periodicals archive ?
compared to SGLT-2 inhibitors NMA may be biased due to differences in patient characteristics between trials, most notably duration of diabetes, and the number of concomitant oral antidiabetic drugs.
The author suggests the following groups of people purchase this report: Manufacturers of antidiabetic drugs, investors/ research institutions interested in Chinese medicine market, any interest in the Chinese medicine market, please contact CRI for customized survey service.
The efficacy and safety of Tresiba used in combination with mealtime insulin or used as add-on to common background oral antidiabetic drugs for the treatment of patients with type-2 diabetes were evaluated in four 26-week and two 52-week active-controlled clinical trials involving 2,702 participants exposed to Tresiba.
There exists some apprehension regarding the use of oral antidiabetic drugs during pregnancy," they wrote.
TEHRAN (FNA)- A combination of human stem cell transplantation and antidiabetic drugs proved to be highly effective at improving body weight and glucose metabolism in a mouse model of type 2 diabetes.
Higher frequency of weight gain and edema was observed in patients taking both LYRICA and thiazolidinedione antidiabetic drugs.
Unpublished data suggest that a class of antidiabetic drugs known as incretin mimetics may raise the risk of pancreatitis and precancerous changes (metaplasia) in the pancreatic duct in patients with type 2 (non-insulin-dependent) diabetes.
Five classes of oral antidiabetic drugs (OHDs) that are available which work via four different mechanisms are namely those that (i) enhance secretion of insulin in pancreas (sulfonylurea & non-sulfonylurea); (ii) decrease glucose release from the liver (biguanides); (iii) reduce gastrointestinal absorption of carbohydrates ([alpha]-glucosidase inhibitor); and (iv) improve peripheral glucose disposal (biguanides and thiazolidinediones) (Cheng and Fantus 2005).
Although a new generation of antidiabetic drugs which target this receptor to promote insulin tolerance and production is currently being tested, until now little has been known about precisely how the expression of GPR40 is controlled
Usually, we prescribe drugs such as metfornin, gliptin and byetta which balances the weight gain side effects of antidiabetic drugs," says Dr Ambrish Mittal, chairman, Endocrinology, Medanta - The Medicity.
CHIANG, CW; CHIU, HF; CHEN, CY; WU, HL & YANG, CY 2006: Trends in the use of oral antidiabetic drugs by outpatients in Taiwan: 1997-2003.
After a review of postmarketing adverse event reports, FDA determined that an updated label with a boxed warning on the risks of heart failure was needed for the entire thiazolidinedione class of antidiabetic drugs.