Metformin

Metformin is a medication that is primarily meant for regulating the blood glucose levels. However, the administration of the drug also results in a lower LDL cholesterol and triglyceride levels. Metformin is mainly taken for the treatment of diabetes type 2, usually as monotherapy or in a combination with other drugs. Efficacy of metformin is analysed by measuring the glucose levels in the blood or by determining the presence of glycated haemoglobin (HbA1c), the amount of which should not be higher than 7 per cent, otherwise the use of metformin is considered to be ineffective. Although metformin is the first treatment of choice for diabetes type 2, its effectiveness greatly varies between individuals. The most important factors that influence the effectiveness of metformin are the SLC22A1 and C11ORF65 genes.

The mechanism of metformin activity

Metformin works mainly in two basic ways: by improving the sensitivity of the organism to insulin and by inhibiting the glucose production in the liver.

Hepatic synthesis of glucose takes place three times faster in people suffering from diabetes type 2 than in healthy organisms. This is due to the inefficient activity of the enzyme AMP-activated protein kinase (AMPK), which plays an important role in the regulation of insulin activity and energy balance of the whole body, and also participates in the metabolism of glucose and fat. Metformin affects the activity of the enzyme AMPK in order to reduce the glucose production by one-third, resulting in a low blood glucose level. Metformin lowers the level of glucose in the blood through other mechanisms: by slowing down the absorption of glucose from the intestine into the blood, by increasing glucose uptake in the muscle cells, by reducing its absorption in the digestive tract and by increasing the oxidation of fatty acids.

The efficacy of metformin is primarily affected by polymorphisms in two genes. The SLC22A1 gene encodes the trans-membrane transporter 1 (OCT1) important for the transport of metformin to the cells and outside of the cells, while the other polymorphism is located in the C11ORF65 gene. This gene regulates the activity of the ATM gene, which is responsible for the phosphorylation and the activation of the AMPK enzyme.