How Do SulfonylureasThiazolidinediones Work?

Sulfonylureas/thiazolidinediones 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 also 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. Thiazolidinediones (also known as “glitazones”) act as “insulin sensitizer" because they attach to the insulin receptors on the cells which increases the cell’s sensitivity to insulin (a hormone responsible for controlling glucose in the body) and thus helps in excretion of glucose from the body.

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/thiazolidinediones 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.
• Thiazolidinediones:     
  • Act as "insulin sensitizers" because they attach to the insulin receptors (peroxisome proliferator-activated receptor gamma) on the fat cells throughout the body, which increases cell’s response to the insulin, leading to excretion of glucose from the body.
  • In addition, they increase the level of a natural substance “incretins” which help to control blood sugar by increasing insulin release, particularly after a meal.

Sulfonylureas/thiazolidinediones 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
• Abdominal pain
• Sore throat
• Muscle pain
• Headache
• Loss of appetite
• Weakness

Other rare side effects include:

• Upper respiratory tract infection
• Lower limb edema
• Weight gain
• Dizziness (feeling faint, weak, or unsteady)
• Cardiac failure (a chronic progressive condition that affects the pumping power of the heart muscle) 
• Increased fracture risk
• Anemia (low number of red blood cells)
• 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/thiazolidinediones include:

• Avandaryl
• Duetact
• Glimepride/pioglitazone
• Glimepride/rosiglitazone