Metformin, brand name Glucophage, is an entirely different kind of glucose-lowering medication. Outside the United States, it's called Benoformin,

Dextin, Diabex, Diaformin, Fornidd, Glucoform, Gluformin, Metforal, Metomin, and Orabet.

More than 20 years ago, the United States banned a sister medication called phenformin because of an association with a fatal complication. Metformin has been used in Europe for years without much trouble and was finally approved in this country in 1995. Metformin is rarely, and perhaps never, associated with the fatal complication lactic acidosis that caused phenformin to be banned. A study reported in the Archives of Internal Medicine in November 2003 stated that no evidence exists to date that metformin therapy leads to lactic acidosis.

Metformin has the following characteristics:

¡^ It lowers the blood glucose mainly by reducing the production of glucose from the liver (the hepatic glucose output).

¡^ It works for both type 1 and type 2 diabetes, because (unlike the sulfony-lureas) it does not depend on stimulating insulin to work.

¡^ Used by itself (monotherapy), it does not cause hypoglycemia.

¡^ It may increase the sensitivity of the muscle cells to insulin and slow the uptake of glucose from the intestine.

¡^ It must be taken with food because it causes gastrointestinal irritation, but this side effect declines with time.

It's available in 500 mg, 850 mg, and 1,000 mg tablets.

¡^ A relatively inexpensive generic form is available, which is just as good as any of the brand name forms.

¡^ The maximum dose is 2,500 mg taken in divided doses with each meal.

¡ It's often associated with weight loss, possibly from the gastrointestinal irritation or because of a loss of taste for food.

¡ It's not recommended when you have significant liver disease, kidney disease, or heart failure.

¡ It's usually stopped for a day or two before surgery or an x-ray study using a dye.

¡ It's not recommended for use in alcoholics.

¡ It's not recommended for use in pregnancy or by a nursing mother.

¡^ When given in combination with the sulfonylureas, hypoglycemia can occur. If low blood glucose is persistent, the dose of sulfonylurea is reduced.

Metformin can be a very useful drug, especially when fasting hyperglycemia (high blood glucose upon awakening) is present. Metformin has some positive effects on the blood fats, causing a decrease in triglycerides and LDL cholesterol and an increase in HDL cholesterol. About 10 percent of patients fail to respond to it when it is first used, and the secondary failure rate is 5 to 10 percent a year. It occasionally causes a decrease in the absorption of vitamin B12, a vitamin that is important for the blood and the nervous system.

Bristol-Myers Squibb, the maker of the brand name of metformin, Glucophage, and other drug makers have come up with new preparations of metformin, which, they believe, have some advantages over the original drug:

i Glucophage XR: The original preparation of metformin has to be taken at each meal. Glucophage XR lasts for 24 hours and comes in a 500 mg strength. Its longer lasting effects help overcome the problem of patients not taking their medication the required multiple times a day. Glumetza is the same drug by Biovail Phamaceuticals.

i Glucovance: This pill combines glyburide (a sulfonylurea described in the previous section) with metformin at a dose of 250 or 500 mg. The various combinations are 1.25 mg of glyburide with 250 mg metformin, 2.5 mg glyburide with 500 mg metformin, and 5 mg glyburide with 500 mg metformin. The advantage is the convenience of having to take only one pill instead of two. Glyburide/metformin is the generic form.

i Metaglip: Made by Bristol-Myers Squibb, combines metformin 250 mg and glipizide 2.5 mg. Glipazide/metformin is the generic form that also comes in 500 mg/5 mg.

i Avandamet: This drug is a combination of 4 mg of Avandia (which I describe in the section "Rosiglitazone," later in this chapter) and 500 mg of metformin. This is a potent combination of two drugs that act differently to improve insulin sensitivity. Avandia has been associated with increased heart attacks. I do not recommend this combination.

i ACTOsplus Met: Combines 500 or 850 mg metformin with 15 mg Actos, discussed under the section "Pioglitazone." It is made by Takeda.

i Janumet: Combines 500 or 1000 mg metformin with 50 mg sitagliptin, a member of a new class of drugs called DPP-4 inhibitors (see below). It is made by Merck.

In my experience, the combination drugs work better than giving two drugs separately. This may reflect the greater compliance that results when a single pill is given compared to two separate pills. If you are already taking both of the drugs separately that are available in a combination pill, ask your doctor about getting the single pill that contains both.

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