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Antidiabetic Drugs

Definition, Purpose, Description, Recommended dosage, Precautions, Interactions

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


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 towards increasing insulin secretion, increasing insulin sensitivity, or increasing insulin penetration of the cells.


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

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 action of insulin, and permit glucose control over longer periods of time.

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 glucose production, decreases intestinal absorption of glucose and increases peripheral glucose uptake and utilization. Metformin may be used as monotherapy, 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 which enhance insulin secretion.

Rosiglitazone (Avandia) and pioglitazone (Actos) and the 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 metoformin 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. Review specific literature.


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 may also 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 may also 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 of 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

Antidiabetic Drugs

Antidiabetic Drugs
Brand Name (Generic Name) Possible Common Side Effects Include:
*Insulin is the generic name for several brands which may be animal-based, human-based, or synthetic.
Diabinese (chlorpropamide) Diarrhea, nausea, loss of appetite
Glucotrol (glipizide) Dizziness, fatigue, headache, nervousness
*Insulin Mild allergic reactions, decreased blood pressure, rash, shortness of breath
Micronase (glyburide) Nausea, heartburn, bloating
orinase (tolbutamide) Nausea, heartburn, bloating

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 switch 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, breastfeeding 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. Alpha-glucosidase 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 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 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 are generally well tolerated, however they are structurally related to an earlier drug, troglitazone, which was associated with liver function problems. 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.


The sulfonylureas have a particularly long list of drug interactions, several of which may be severe. 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.

Review the specific literature of each drugs for possible drug-drug or food-drug interactions.



Hingley, Audrey. "Diabetes Demands a Trial of Treatments." FDA Consumer 31 (May-June 1997): 33.


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.


National Institute of Diabetes and Digestive and Kidney Diseases. <http://www.niddk.nih.gov>.

Samuel Uretsky, PharmD


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.

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