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Oral Medicines for Type 2 Diabetes

by Patti Geil, M.S., R.D., C.D.E., and Laura Hieronymus, M.S.Ed., A.P.R.N., B.C.-A.D.M., C.D.E.

Biguanides. Only one biguanide, namely metformin (Glucophage), is currently approved for marketing in the United States. Metformin is most effective in overweight or obese people who are insulin-resistant. It works by reducing liver glucose output, and it may also improve insulin sensitivity in the liver and muscle and fat cells. Metformin appears to suppress appetite and also lower cardiovascular risk factors without risk of hypoglycemia. Its major disadvantage is that it can cause gastrointestinal problems, particularly at higher doses.

A rare but serious side effect of metformin is lactic acidosis, in which lactic acid builds up in the bloodstream. People with heart, lung, kidney, or liver problems and those who drink alcohol heavily are more prone to developing lactic acidosis.

Sulfonylureas. This class of drugs—which includes glipizide (Glucotrol, Glucotrol XL), glyburide (DiaBeta, Glynase, Micronase), glimepiride (Amaryl), and the less commonly used chlorpropamide (Diabinese), tolazamide (Tolinase), and tolbutamide (Orinase)—works most successfully in those who have recently been diagnosed with Type 2 diabetes. Sulfonylureas are “pancreas stimulators” that cause the beta cells to release more insulin. They are generally inexpensive, and they reduce fasting blood glucose levels effectively. Side effects associated with their use include weight gain and hypoglycemia.

Meglitinides and d-phenylalanine derivatives. There is one meglitinide on the market, repaglinide (Prandin), and one d-phenylalanine derivative, nateglinide (Starlix). These drugs are not sulfonylureas, but their mechanism of action closely resembles them. They stimulate the release of insulin from pancreatic beta cells, but they take effect more quickly, and their effects last for only a short amount of time. They are also most effective in people recently diagnosed with Type 2 diabetes, and they act to control postprandial blood glucose elevations.

Either drug should be taken immediately before a meal; if you skip a meal, don’t take a pill or you will risk hypoglycemia. If you have trouble maintaining a regular eating pattern, you may have a problem remembering to take these pills.

Thiazolidinediones. Thiazolidinediones, often referred to as TZDs or glitazones, are insulin sensitizers, designed to help insulin work better in muscle and fat tissue while protecting insulin-producing beta cells from further damage. The first approved drug in this class, troglitazone (Rezulin), was removed from the market in 2000 because of reports of severe liver toxicity. The currently available TZDs, pioglitazone (Actos) and rosiglitazone (Avandia), have not been associated with this problem. Nonetheless, periodic liver function tests are still recommended for people taking either pioglitazone or rosiglitazone.

Because the TZDs don’t increase insulin secretion, they do not carry the risk of hypoglycemia. People who already use insulin may find that adding a TZD to their diabetes regimen may help to significantly reduce their daily insulin requirement. However, TZDs are costly, and significant weight gain has been reported with their use.

Special considerations

Oral blood-glucose-lowering medicines are generally not recommended for use in Type 1 diabetes because of the total lack of pancreatic insulin production that characterizes this condition. However, research has shown that the alpha-glucosidase inhibitors may be helpful in controlling postprandial blood glucose in people with Type 1 diabetes because of the drug’s ability to block the absorption of carbohydrate. Also, because of the insulin resistance that occurs in puberty, metformin has been shown to improve metabolic control in adolescents with Type 1 diabetes. This effect seems to be associated with improved insulin-induced glucose uptake by tissues. In both situations, oral medicines are not a substitute for insulin. They are used in addition to the insulin regimen. It should be noted that these are “off-label” uses of these drugs; neither is approved by the U.S. Food and Drug Administration for marketing as a treatment for Type 1 diabetes.

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