Products
Metformin is commercially available in many countries in the form of film-coated tablets and has been available since 1960. In addition to the original Glucophage, numerous generics are available today. Metformin is often combined with various other antidiabetic drugs fix. It has been used medically since 1957. Other antidiabetic biguanides such as phenformin and buformin are no longer commercially available due to poorer tolerability.
Structure and properties
Metformin (C4H11N5, Mr = 129.2 g/mol) is present in the drugs as metformin hydrochloride, a white, almost odorless, and bitter-tasting crystalline powder that is readily soluble in water. It is a dimethylated biguanide derived from guanidine.
Effects
Metformin (ATC A10BA02) has antidiabetic and antihyperglycemic properties. It inhibits the absorption of glucose in the intestine, inhibits gluconeogenesis and glycogenolysis in the liver, decreases insulin resistance, and increases glucose uptake into tissues, such as muscle. Metformin is therefore also known as an “insulin sensitizer.” Unlike the sulfonylureas, it does not stimulate insulin secretion and does not induce hypoglycemia. The half-life is in the range of 17 to 18 hours.
Indications
For the treatment of type 2 diabetes mellitus, as monotherapy or in combination with other antidiabetic agents or insulins. Metformin is the first-line agent according to many guidelines. Metformin can also be used in type 1 diabetes, as an adjunct to insulin therapy.
Dosage
According to the drug label. Tablets are usually taken whole with food (or after food) one to three times daily. Tablets should be divided only when directed to do so because metformin has a bitter taste. Therapy is started gradually.
Contraindications
- Hypersensitivity
- Metabolic acidosis
- Diabetic coma and precoma
- Severe renal failure
- Acute conditions that may impair renal function.
- Intravascular application of iodine-containing contrast agents for radiographic examinations (see the SmPC).
- Diseases that may cause tissue hypoxia.
- Liver failure
- Acute alcohol intoxication, alcoholism
These contraindications are primarily aimed at preventing the development of lactic acidosis. Full precautions can be found in the drug label.
Interactions
Numerous substances have an effect on blood glucose. Metformin undergoes active tubular secretion at the kidneys and is a substrate of the organic cation transporters OCT1 and OCT2. Corresponding interactions may occur, for example, with cimetidine.
Adverse effects
The most common potential adverse effects include gastrointestinal disturbances such as a metallic taste, nausea, vomiting, diarrhea, abdominal pain, and lack of appetite, especially at the beginning of treatment. Retarded preparations are somewhat better tolerated in this regard. Metformin may lower vitamin B12 levels, and supplementation may be indicated. It is unlikely to cause hypoglycemia and does not cause weight gain. A serious adverse effect, which in the worst case can be fatal, is lactic acidosis. However, according to the literature, it occurs extremely rarely and mainly in the presence of risk factors. The relationship between metformin therapy and the development of lactic acidosis is controversial (e.g. Salpeter et al., 2006).
