Metformin
(March 2000 Molecule of the Month)Metformin
(March 2000 Molecule of the Month)Metformin is an oral medication designed to help control elevated blood sugar levels in NIDDM (non-insulin-dependant diabetes mellitus). It is believed to work by inhibiting hepatic glucose production and increasing the sensitivity of peripheral tissues to insulin. Metformin’s brand name is Glucophage and it has been used clinically in Europe continually since 1970. However, in America in 1977 the drug was removed from the U.S market amid safety concerns about the related drug Phenformin. This was seen to occasionally promote lactic acidosis, a potentially fatal build-up of lactic acid in the blood.
The medicine does not increase how much insulin the pancreas makes but acts on the liver preventing it from producing excess sugar and stopping hyperglycemia (high blood sugar).
Metformin is primarily suited for the treatment of subjects with non-insulin-dependent diabetes mellitus (Type II diabetes). Compared to other antidiabetic agents, it has the advantages of lowering rather than increasing body weight, of not causing hypoglycemia, and of entailing a reduction of triglycerides and LDL-cholesterol levels. Metformin is therefore recommended in single drug therapy especially for obese subjects. In the majority of the treated subjects a lowering of blood glucose levels by at least 25% is achieved (i.e. almost identical results as with sulfonylureas at the beginning of treatment).
Metformin also helps lower the fatty blood components triglycerides and cholesterol that are often high in people with Type II diabetes.
In December 1994, the U.S. Food and Drug Administration (FDA) approved the use of metformin for the treatment of Type 2 diabetes. Metformin was approved for use either alone or with sulfonylureas, a commonly used group of diabetes medicines. Metformin's brand name is Glucophage.
Metformin
can also be combined with other antidiabetic agents. It can thus e.g. be used
when there is secondary failure with sulfonylureas. Occasionally a small dose
of metformin combined with a sulfonylurea is sufficient to restore an adequate
diabetic control. In carefully selected cases, a combination with insulin can
also be sensible - particularly for obese subjects with relative insulin resistance.
Metformin quite frequently (5 to 20%) causes gastrointestinal problems such as nausea, stomach pain, bloating, diarrhea and malabsorption of vitamin B12 and folic acid. These side effects usually go away soon after the metformin is started and occur less often if metformin is taken with food. Another possible problem with metformin is a rare but serious condition called lactic acidosis, when your tissues do not get enough oxygen to survive. To avoid this problem, metformin should not be given to people with kidney or liver disease, severe heart failure, or a history of alcohol abuse.
Skin rashes are rare. The platelet inhibition hardly has any clinical disadvantages.
Metformin very rarely causes a dangerous lactic acidosis (roughly 1 case on every 10,000 patient years, mortality rate about 40%). Most cases affect individuals with risk factors, especially impaired renal functions. Other biguanides cause lactic acidoses (e.g buformin) more often. The risk of a lactic acidosis under metformin is no greater than the risk of a severe hypoglycemia under sulfonylureas.