How Do Sulfonylureas Biguanides Work?

Sulfonylureas/biguanides are oral antidiabetic combination drugs used with a proper diet and exercise to control high blood sugar in people with type 2 diabetes mellitus (T2DM). T2DM is a slowly progressive metabolic disorder caused by a combination of genetic and lifestyle factors that promote chronically elevated blood sugar levels. Controlling high blood sugar helps in preventing kidney damage, blindness, nerve problems, loss of limbs, and sexual function problems and may reduce the risk for heart attack or stroke (loss of blood flow to part of the brain).

Sulfonylureas work by stimulating the production of insulin in the pancreas and increasing the effectiveness of insulin in the body. Biguanides work by preventing the production of glucose in the liver, improving the body’s sensitivity to insulin, and reducing the amount of sugar absorbed by the intestines. Insulin is a peptide hormone produced by the beta cells of the pancreas to help metabolize food and use it for energy throughout the body. After a meal, insulin promotes the uptake of glucose (a type of sugar found in many carbohydrates) from the blood into internal organs and tissues such as the liver, fat cells, and skeletal muscles.

Sulfonylureas/biguanides are not used to treat insulin-dependent or type 1 diabetes (a condition in which the body does not produce insulin and therefore cannot control the amount of sugar in the blood) and diabetic ketoacidosis (increased ketones in the blood or urine).

Sulfonylureas/biguanides work in the following ways:

• Sulfonylureas:
  • Lower blood sugar levels by stimulating the production of natural insulin in the beta cells of the pancreas.
  • Increase the body’s tendency to use insulin efficiently.
  • Increase the peripheral glucose utilization, decrease hepatic gluconeogenesis (generation of glucose in the liver), and may increase the number and sensitivity of insulin receptors.
  • Insulin secretion by pancreatic beta cells is partly controlled by cellular membrane potential regulated through an inverse relationship between the activity of cell membrane adenosine triphosphate (ATP)-sensitive potassium channels and extracellular glucose concentrations.
  • Extracellular glucose enters the cell via glucose transporters 2. Once inside the cell, glucose is metabolized to produce ATP (a source of energy for use and storage at the cellular level).
  • They increase insulin release by inhibiting ATP-sensitive potassium channels that depolarize the beta cells, in turn opening calcium channels that result in the influx of calcium. Increased intracellular calcium induces insulin secretion.
• Biguanides:
  • Reduce the production of glucose during digestion by decreasing the amount of glucose absorbed from the food.
  • Prevent the liver from converting fats and amino acids into glucose.
  • Increase the excretion of sugar by the kidneys.
  • Decrease the amount of sugar that the body absorbs through the stomach and intestines.
  • In addition, they activate an enzyme (AMPK) that increases the sensitivity to insulin (a natural substance that controls the amount of glucose in the blood produced by the pancreas), helping cells to respond more effectively to insulin and use more glucose as energy, and thus reducing the concentration of glucose in the bloodstream.

Sulfonylureas/biguanides are used as an adjunct to diet and exercise to improve glycemic control in adults with T2DM.

Some of the common side effects include:

• Diarrhea
• Nausea
• Vomiting
• Stomach upset
• Abdominal pain
• Sore throat
• Muscle pain
• Headache
• Loss of appetite
• Weakness
• Heartburn (burning pain in the chest)

Other rare side effects include:

• Upper respiratory tract infection
• Lower limb edema
• Weight gain
• Dizziness (feeling faint, weak, or unsteady)
• Fever
• Asthenia (abnormal physical weakness or lack of energy)
• Leukopenia (low white blood cells)
• Anemia (low number of red blood cells)
• Lactic acidosis (increased lactic acid in the bloodstream which is produced when oxygen levels are low in cells within the areas of the body where metabolism occurs)
• Upper respiratory tract infection
• Hypoglycemia (low blood sugar level)
  • Sudden sweating
  • Fast heartbeat
  • Blurred vision
  • Tingling in hands/feet
• Signs of kidney problems 
  • Change in the amount of urine
  • Dark urine
  • Swelling in legs/feet

Information contained herein is not intended to cover all possible side effects, precautions, warnings, drug interactions, allergic reactions, or adverse effects. Check with your doctor or pharmacist to make sure these drugs do not cause any harm when you take them along with other medicines. Never stop taking your medication and never change your dose or frequency without consulting your doctor.

Generic and brand names of sulfonylureas/biguanides include:

• Glipizide/metformin
• Glucovance
• Glyburide/metformin
• Metaglip