At present only one biguanide is available, metformin. Due to high risk of lactic acidosis, phenformin is no more available. Biguanides are different from sulfonylureas, and do not cause hypoglycemia as they do not stimulate beta-cells of pancreas. Metformin improve lipid profile and is preferred among obese diabetic patients.

Mechanism of Action of Biguanides:

The exact mechanism of action of biguanides is not clearly understood. Although biguanides do not cause (increase) insulin release, presence of some insulin is essential for the action of biguanides. Some of the possible explanations of mechanism of action of biguanides are given here:

• Biguanides suppress gluconeogenesis in liver and reduce glucose output from liver. This is considered as the main mechanism of action of biguanides.
• Biguanides increase insulin mediated glucose utilization in muscles and fat. Biguanides increase transport of glucose from intracellular site to plasma by GLUT1 (glucose transporter 1) although it is a minor transporter of glucose, the major being GLUT4, which is not affected by biguanides.
• Reduce absorption of glucose, other hexoses, amino acids and vitamin B12 from intestines.
• Promote use of glucose by increasing anaerobic glycolysis by interfering mitochondrial respiratory chain.

The last two mechanisms are minor and do not contribute much in therapeutic effects of biguanides in type-2 diabetes.

Side effects of biguanides:

Biguanides have several side effects but not serious. Due to high risk of serious lactic acidosis fenformin was withdrawn from market. Metformin has side effects such as loss of appetite, abdominal pain, nausea, mild diarrhea, metallic taste, fatigue, lactic acidosis, vitamin B12 deficiency etc. Hypoglycemia is only seen in overdose of metformin and a rare side effect.

Lactic acidosis:

Small increase in lactic acid level in blood can occur with metformin, but lactic acidosis is rare as lactic acid in liver cells is low. Alcohol in large quantity can precipitate lactic acidosis. The incidence of lactic acidosis is less than 1 per 10,000 patients per year.

Vitamin B12 deficiency:

This is due to interference of absorption of vitamin B12 from intestine and can occur on long term use in high doses.

Biguanides (metformin) should not be used in patients with low blood pressure, chronic alcoholics (high risk of lactic acidosis), and in patients with liver, kidney, respiratory and heart disease.