Biguanides

Members of this family: Metformin

History  

Biguanides are one of the oldest group of medications used in the treatment of diabetes. They are the backbone of treatment in most published guidelines. Metformin the only member of this group used in medicine today was first produced in 1922 and was registered for use in South Africa in August of 1974.

Its history can be traced back to the 1700s, where the plant Goat’s rue (Galega Officialis) was used to treat thirst and frequent urination, symptoms associated with diabetes. Studies done in 1918 revealed that the plant was rich in guanidine. Guanidine was shown to lower blood sugar in animals.

Several products were produced from the plant in the 1920’s, some went on to be used in the treatment of diabetes. Their use was overtaken and gradually abandoned after the discovery of insulin in 1922.Metformin was deemed not good enough for use in the treatment of diabetes at the time.

 In 1949 researchers in the Philippines tested metformin for possible use in the treatment of malaria. It was found to be helpful in treating influenza and was then used as an anti-influenza agent. Blood glucose lowering was observed in several patients.

In 1956 researchers in Paris re-assessed the glucose lowering properties of biguanides. They unknowingly repeated studies done in the 1920s and were impressed by their findings on metformin. They took it a step further and tested metformin at a diabetes clinic and published their findings in 1957.The medication was nicknamed “glucose-phage” (glucose -eater).

How does it work?

Metformin lowers blood sugar in three different ways:

1. Metformin reduces or stops the production of glucose by the liver . The liver plays an important role in blood glucose control. Between meals and overnight the liver produces and releases glucose into the blood stream to meet the body’s energy needs.
2. Metformin improves insulin resistance by helping the body restore its ability to respond to insulin.
3. Metformin reduces the amount of glucose absorbed by the intestines. Glucose the product of carbohydrate breakdown is absorbed from the stomach by the small intestines and transported into the blood stream.

Factors to consider when using metformin

Risk of hypoglycaemia

Metformin does not cause hypoglycaemia. Individuals on metformin may experience hypoglycaemia due to dietary changes, skipped meals, and changes in exercise routine. The use of metformin with other glucose lowering medications increases the risk of hypoglycaemia.

Glycaemic control

Metformin when used alone has been shown to lower HbA1c by 1% -2%.

Effect on weight

Metformin has been shown to cause weight loss. The amount of weight loss varies. Some researchers report weight loss of up to 5% of total body weight. Meaning that an individual weighing 80kg might lose up to 4kg within a year of starting treatment. Another study reported an average weight loss of 2kg due to metformin.

Research is ongoing on the potential use of metformin as a weight loss medication for non- diabetic individuals.

Benefits to heart and kidneys

Type 2 diabetes increases one’s risk of developing heart disease. Metformin has been shown to provide long term heart protection for those with type 2 diabetes. The medication also helps in controlling cholesterol, which is important for heart health. Studies have shown that metformin reduces risk of heart attacks, risk of death due to heart related problems and risk of developing heart conditions.

 Metformin provides no protection for the kidneys.

Cost

Metformin remains one of the most cost-effective medications available for the treatment of type 2 diabetes. It is the recommended first line treatment in most published guidelines.

Side effects

Stomach related side effects are common in individuals starting metformin. They include nausea and vomiting, abdominal pain, diarrhoea, loss of appetite and taste disturbances (metallic taste in the mouth ).Side effects usually go away after about two weeks of starting treatment. If side effects continue for longer or become unbearable talk to your doctor or pharmacist about switching to an extended release preparation.

Skin related side effects though not common can be caused by metformin. These include itching, rashes and flushed skin (redness of the skin)

Long term use of metformin has been shown to cause Vitamin B12 deficiency, which can also affect the skin resulting in dark spots on the skin involving the face, mouth and hands, nail abnormalities and skin darkening.

Black box warning

Metformin comes with a box warning for lactic acidosis. Lactic acidosis is a very rare and serious side effect associated with the use of biguanides. The condition requires hospitalisation and should be treated as a medical emergency.

 A Black Box warning is the strongest safety warning that can be placed on a medication. It is there to warn healthcare professionals and patients about a risk associated with a medication that could cause serious injury or even death.

Useful tips when using metformin

• Metformin can be taken before or after a meal.
• Taking metformin after a meal helps relieve stomach related side effects.
• Metformin extended release tablets when taken daily should preferably be taken with the evening meal.
• Tell your doctor if you have liver or kidney problems .
• If going to hospital for tests or surgery always confirm with your doctor if you should stop metformin.