Biguanide
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Biguanides (ATC A10 BA) form a class of oral antihyperglycemic drugs used for diabetes mellitus or prediabetes treatment.
Examples
Examples of biguanides:
- metformin - widely used in treatment of diabetes mellitus type 2 combined with obesity
- phenformin - withdrawn from the market in most countries due to toxic effects
- buformin - withdrawn from the market due to toxic effects
Proguanil is a biguanide used not for diabetes, but rather as an antimalarial drug.
History
Galega officinalis was used for diabetes treatment in traditional medicine for centuries. In the 1920s, guanidine compounds were discovered in Galega extracts. Animal studies showed that these compunds lowered blood glucose levels. Some less toxic derivatives, synthalin A and synthalin B, were used for diabetes treatment, but after the discovery of insulin they were forgotten for the next several decades. Biguanides were reintroduced into Type 2 diabetes treatment in the late 1950s. Initially phenformin was widely used, but its potential for sometimes fatal lactic acidosis resulted in its withdrawal from pharmacotherapy in most pharmacopeias (in the U.S. in 1977). Metformin has a much better safety profile, and it is the principal biguanide drug used in pharmacotherapy worldwide.
Pharmacotherapy
Biguanides do not affect the output of insulin, unlike other hypoglycemic agents such as sulfonylureas and meglitinides. Therefore, they are not only effective in Type 2 diabetics, but they can also be effective in Type 1 patients in concert with insulin therapy.
Mode of action
The exact mode of action of biguanides is not fully elucidated. However, in hyperinsulinemia, biguanides can lower fasting levels of insulin in plasma. Their therapeutic uses derive from their tendency to reduce gluconeogenesis in the liver, and as a result, reduces the level of glucose in the blood. Biguanides also tend to make the cells of the body more willing to absorb glucose already present in the blood stream, and there again reducing the level of glucose in the plasma.
Side effects and toxicity
The most common side effect is diarrhea and dyspepsia, occurring in up to 30% of patients. The most important and serious side effect is lactic acidosis. Phenformin and buformin are more prone to cause acidosis than metformin therefore they have been practically replaced by it. However, when metformin is combined with other drugs (combination therapy), hypoglycemia and other side effects are possible.
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