Oral Medication - Treatment For Type 2 Diabetes: Diabetes A Plan For Living

Content provided by the Faculty of the Harvard Medical School

Oral medication

Until fairly recently, the only oral diabetes drugs available in America were sulfonylureas, medications that drive down blood sugar by increasing insulin production. When they failed, insulin was required. During the last decade, however, the number of medications has more than tripled, and whole new classes of medications have been introduced. Today's diabetes drugs address insulin resistance and production, as well as other causes of high blood sugar levels (see Table 5). And not only do doctors now have a wider range of drugs to choose from, they also use them more aggressively in combination.

Doctors don't usually recommend oral drugs when major surgery is planned or for people with advanced heart, liver, or kidney disease.

Sulfonylureas

Sulfonylureas, the oldest class of oral antidiabetic medications, work by stimulating your pancreas to make more insulin. These drugs are taken once or twice a day; most people begin with a low dosage that's gradually increased. Sulfonylureas are less effective in thin type 2 people, and approximately 10%–20% of people who try them don't reap any benefit. Moreover, about half of those who benefit initially find that the drugs' effectiveness declines during the first five years.

An essential consideration is the side effects of these medications. All sulfonylureas carry the risk of hypoglycemia, which can be particularly dangerous in the elderly. Drinking alcohol or missing a meal can precipitate an episode. In addition, some people who drink alcohol while taking sulfonylureas (especially chlorpropamide) become flushed and suffer nausea, stomach pains, and a racing heartbeat. It's common for people taking sulfonylureas to gain some weight. People who are allergic to sulfa drugs should not take sulfonylureas. Further, some studies suggest a possible link between sulfonylureas and cardiovascular disease.

Biguanides

Biguanides block the liver's release of glucose and reduce its resistance to insulin. Thus they lower blood sugar levels without stimulating insulin secretion. Typically, metformin (Glucophage), which comes in pill form, is taken two or three times a day with meals, although a longer-acting formula may be taken once or twice a day.

Metformin has several advantages over sulfonylureas. It works well in overweight and average-weight people. It lowers blood sugar levels as effectively as the sulfonylureas without promoting weight gain, and it doesn't usually cause hypoglycemia when used by itself.

On the other hand, it can sometimes cause unpleasant gastrointestinal effects, such as nausea, flatulence, and diarrhea. But you can often minimize these effects by starting with a small dose and taking it with a meal. Metformin also puts people at risk for lactic acidosis, a very rare but potentially lethal condition in which blood lactic acid levels increase. Because of this danger, people with impaired kidney function, congestive heart failure, liver disease, or circulatory problems should not take this drug. Otherwise, it is extremely safe. Like the sulfonylureas, however, its benefits seem to diminish somewhat over time.

Alpha-glucosidase inhibitors

Alpha-glucosidase inhibitors hamper the digestive enzyme that breaks carbohydrates into smaller sugars that can be absorbed by the intestines. Because the drug slows the body's digestion and absorption of carbohydrates, sugar levels rise slowly, and the insulin that's produced has time to do its job more effectively. Acarbose (Precose) was the first in this class of drugs to be approved; now, miglitol (Glyset) is also available.

Although weaker than some other drugs for type 2 diabetes, these medications are helpful in limiting the surges in blood glucose that occur after meals. Acarbose and miglitol are not absorbed into the bloodstream and are very safe. They often cause annoying flatulence and diarrhea, but these side effects usually diminish with time and may be eased by building up the dosage slowly.

Thiazolidinediones

Thiazolidinediones (TZDs) are the first diabetes drugs designed to reduce insulin resistance. Troglitazone (Rezulin), a "first-generation" TZD, was pulled from the market in March 2000 after its use was connected to deaths from liver failure. However, rosiglitazone (Avandia) and pioglitazone (Actos) are still on the market and don't appear to cause liver disease. They work most effectively in combination with other antidiabetic medications.

Still, the FDA has recommended that labels for Avandia and Actos state that drugs in this class have been linked to liver problems. Anyone taking TZDs should have their liver enzymes checked at the start of treatment and every two months during the first year of therapy. If you experience nausea, vomiting, abdominal pain, fatigue, anorexia, or dark urine, have your liver enzymes checked. If you develop jaundice, stop taking the drug and contact a doctor immediately. Additionally, all the TZDs can cause fluid retention and may increase the risk of heart failure.

Meglitinides

Repaglinide (Prandin) and nateglinide (Starlix) are some of the latest additions to the arsenal aimed at type 2 diabetes. Like the sulfonylureas, they stimulate insulin secretion by the pancreas. But they act more rapidly and last for less time than the sulfonylureas. As a result, they reduce the chances of hypoglycemia and are safer for the elderly and people with reduced kidney function. Doses can be adjusted somewhat before meals. If you skip a meal, you can also skip a pill; if you have an extra meal, take another pill.

Last updated:	January 23, 2007