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Sulfonylureas

A class of drugs used in treating Type 2 diabetes. The first line of treatment for Type 2 diabetes consists of dietary changes and exercise, which help people with diabetes lose weight, improve the way their bodies make and use insulin, and lower blood glucose levels. Unfortunately, despite their best efforts, many people either cannot lose weight or cannot maintain their weight loss, or their blood glucose levels are poorly controlled in spite of weight loss. In these people, the only alternative is drug treatment.

Sulfonylurea pills work primarily by stimulating the pancreas to release more insulin. The first-generation sulfonylureas, which have been around for many years, are tolbutamide, tolazamide (brand name Tolinase), and chlorpropamide (Diabinese). Newer, more powerful second-line sulfonylureas, which have fewer side effects, include glipizide (Glucotrol), glyburide (Micronase, Glynase PresTabs, and DiaBeta), and the newest drug, glimepiride (Amaryl). A single-dose, extended-release form of glipizide called Glucotrol XL is also available.

Unfortunately, sulfonylureas do not always succeed in controlling diabetes. With sulfonylurea therapy, some 10% to 20% of people will immediately fail to control their blood glucose levels adequately on the highest recommended dose (a situation called “primary failure”). Sulfonylureas themselves tend to overwork the pancreas until it eventually “burns out” and is unable to secrete an adequate amount of insulin, so roughly 5% to 10% of people who initially respond to sulfonylurea therapy will subsequently fail each year (a situation called “secondary failure”).

There are other problems with sulfonylureas. About 90% of people with Type 2 diabetes are obese, and sulfonylureas tend to make them gain even more weight. Sulfonylureas can also cause hypoglycemia, or abnormally low blood glucose levels, although hypoglycemia is not very common in Type 2 diabetes.

Fortunately, several new types of drugs for treating Type 2 diabetes have come on the market in the United States. Metformin (Glucophage), a type of drug called a biguanide, appears to lower blood glucose levels without increasing insulin secretion, which may help sidestep “beta-cell burnout.” Acarbose (Precose), a type of drug called an alpha-glucosidase inhibitor or “starch blocker,” blocks an enzyme responsible for breaking down carbohydrate in the intestines, thus decreasing the rise of blood glucose levels after meals. Repaglinide (Prandin), a member of another class of beta-cell stimulating drugs called meglitinides, acts in response to rises in blood glucose levels following meals. Pioglitazone (Actos) and rosiglitazone (Avandia), two types of thiazolidinedione, make muscle and fat cells more sensitive to insulin in the bloodstream, resulting in better glucose uptake. Sitagliptin (Januvia) and and saxagliptin (Onglyza) enhance insulin secretion and delay stomach emptying. Exenatide (Byetta) and liraglutid (Victoza) delay stomach emptying and stimulate insulin secretion. Pramlintide (Symlin) slows stomach emptying, suppresses glucagon, and suppresses appetite.

 

 

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