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Controlling Diabetes with Class

By David Mendosa

Last Update: March 28, 2004

Were you just diagnosed with type 2 diabetes? Or are you thinking about switching to a new, more powerful medication? The good news is that nowadays you have a big choice in the oral medications you can use to control diabetes.

Until 1995…they all worked the same way.

As recently as 1995 your only choices were in one family or class of drugs (called sulfonylureas). It was a little like buying one of the first automobiles in the color you liked — as long as you liked black.

Now the pharmaceutical companies have introduced a wide range of oral hypoglycemic agents. Currently, we have well over a dozen different options to choose from. Some of them have Web sites.

Oral hypoglycemic agents are pills that help to you reduce your blood glucose levels. They are not oral insulin. But they do give some people with diabetes normal glucose levels when diet and exercise aren't enough for them to control their diabetes.

These pills work only when your pancreas is producing insulin. They aren't for people with type 1 diabetes, because their pancreases don't produce enough insulin for the pills to work.

We now have five (or six) classes of oral medications, each of which work in a different way, plus various combination pills. Furthermore, your doctor may prescribe for you to take more than one class of these medications at the same time.

Until 1995, other than insulin, the sulfonylurea class of drugs was the only choice for treating type 2 diabetes. You had a big choice of brands, but they all worked the same way.

Sulfonylureas

Sulfonylureas squeeze more insulin out of the beta cells of your pancreas and improve insulin's ability to get glucose into the rest of your body. Cost and how long they work are the major differences among the many drugs in this class.

Brand names for the sulfonylureas in the U.S. include Amaryl® (glimepiride), Dymelor® (acetohexamide), Diabinese® (chlorpropamide), Glucotrol® and Glucotrol XL® (glipizide), Diaßeta® (glyburide), Glynase® (glyburide), Micronase® (glyburide), Orinase® (tolbutamide), and Tolinase® (tolazamide).

Glyburide is also called glibenclamide in most of the world. There are other sulfonylureas that are not marketed in the United States, including gliclazide.

Websites: Amaryl is the only sulfonylurea to have its own Web site, www.amaryl.com. Hoechst Marion Roussel (now Aventis) created the Amaryl site in June 1999. Pfizer has registered the names www.glynase.com and glucotrolxl.com but as of March, 2004, these sites link to the main Pfizer site without giving specific information on these products.

Biguanides

In the 1970's, a biguanide called phenformin (sold under the names D.B.I., Meltrol-50 capsules, and others) had been available in the United States, but phenformin was associated with a life-threatening side effect of lactic acidosis, and phenformin was withdrawn from the U.S. market on November 15, 1978. (Further information is available at the FDA website).

The explosion of drugs available in the United States for controlling blood glucose really began in 1995. In that year, metformin, another drug in the biguanide class, became available in the U.S. after demonstrating much less likelihood of provoking lactic acidosis. Glucophage® (metformin hydrochloride) was developed in France by Lipha S.A. and has been used for decades in Europe. It has quickly become the most prescribed diabetes pill in the U.S.

Glucophage works differently from the sulfonylureas. It increases the sensitivity of your liver and muscle to insulin rather than increasing insulin secretion from your pancreas.

Websites: Bristol-Myers Squibb Company has lots of information about metformin on the Glucophage website, http://www.glucophagexr.com.

Alpha-glucosidase Inhibitors

The third class of drugs approved for diabetes has a mouthful of a name, alpha-glucosidase inhibitors. Drugs in this class delay the digestion of carbohydrates, causing glucose to enter the blood more slowly.

The Food and Drug Administration approved the first drug in this class, Precose® (acarbose), in late 1995. The FDA approved GlysetTM (miglitol) the next year, but it wasn't until early 1999 that this drug actually became available here.

Websites: Bayer has a website for Precose, using the alternate (non-U.S.) brand name of Glucobay, at http://www.precose.com and http://www.glucobay.com (both URLs seem to lead to the same content). Pfizer has registered the name www.glyset.com but as of March 2004 this site links to the main Pfizer site without giving specific information on these products.

Thiazolidinediones

The first thiazolidinedione, troglitazone (Rezulin®) was introduced to the U.S. and Japanese markets in 1997. Unfortunately, the drug could cause liver damage, and it was voluntarily withdrawn from the market by the manufacturer on March 21, 2000. In mid-1999 the FDA approved two new drugs in the class called thiazolidinediones (TZDs). They are Avandia® (rosiglitazone maleate) and ActosTM (piaglitazone hydrochloride). These new "glitazones" make your body more sensitive to its insulin.

Websites: SmithKline Beecham's Avandia site is at www.avandia.com. An Actos site at www.actos.com  is in the works.

Meglitinides

The first medication in the fifth class of drugs, meglitinides, hit the market in 1998. Repaglinide (PrandinTM in the U.S.; NovoNormTM elsewhere) works by stimulating insulin secretion from the beta cells of the pancreas. Prandin's quick onset and short duration of action concentrate its effect around the meal time glucose load. Consequently, it needs to be taken just before each meal.

Another similar drug, nateglinide (Starlix™) (from Novartis) was approved by the U.S. FDA in December 2000.

Websites: Repaglinide: www.prandin.com/ and /www.novonorm.com Nateglinide: http://www.starlix.com

Orlistat

Orlistat (Xenical®) (Roche) is approved by the FDA for weight loss, including use by people with obesity and diabetes. Orlistat works in the digestive system to block about one-third of the fat in the food that is eaten from being digested. Orlistat attaches to lipase enzymes in the gut, and blocks these lipase from breaking down some of the fat; the undigested fat cannot be absorbed and is eliminated in the bowel movements.

Since type 2 diabetes is frequently accompanied by obesity, and since weight loss can help improve glucose tolerance, it might be considered that orlistat be considered a "diabetes pill." Roche has a page devoted to this topic on the Xenical website, at Health befnefits of weight loss: Type 2 diabetes.

Websites: Orlistat: www.xenical.com

Combination Pills

Many of the diabetes pills can be combined to get increased effect to control blood sugar levels. The manufacturers have now developed several combinations, using products from two of the five different classes of diabetes pills. Using fixed-combination pills offer less flexibility in diabetes management: if the dose of one ingredient needs to be adjusted, both would end up being adjusted if a combo pill is being used. Also, the combination pills are presently available only by brand name. They are more expensive, but the benefits of an easier routine may make the added cost worthwhile, if the combination is able to control your diabetes. For example, there may be less pills to swallow, and for people who have insurance for their medications, it's only a single copayment for the combination product. Combination pills for diabetes that are available in the U.S. include:

  • GlucoVance (combination of glyburide and metformin, from Bristol-Myers Squibb) (Approved by FDA July 31, 2000.)
  • Avandamet (combination of rosiglitazone and metformin, from GlaxoSmithKline) (Approved by FDA October 10, 2002.)
  • Metaglip (combination of glipizide and metformin, sold in the U.S. by Bristol-Myers Squibb) (Approved by FDA October 22, 2002.)

Websites: GlucoVance: www.glucovance.com; Avandamet: www.avandamet.com Metaglip: www.metaglip.com

Summary

That's quite a few different medications in five or six classes of drugs, plus combinations! One or more of these are likely to work for you. 


The American Diabetes Association originally published this article on its Web site as one of my “About the Internet” columns.


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