Biguanides (ATC A10 BA) form a class of oral antihyperglycemic drugs used
for diabetes mellitus or prediabetes treatment.
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- phenformin - withdrawn from the market in most countries due to toxic effects
- buformin - withdrawn from the market due to toxic effects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.
Galega officinalis was used for diabetes treatment in traditional medicine
for centuries. In the 1920s, guanidine compounds were discovered in Galega
extracts. It was showed that in animals they lower blood glucose. 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.
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.
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.
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. |