How Do Thiazolidinediones Work?

Reviewed on 1/10/2022


Thiazolidinediones also known as “glitazones” are oral antidiabetic drugs used with a proper diet and exercise to control high blood sugar in people with type 2 diabetes mellitus (T2DM). T2DM is a long-term medical condition in which the body does not use insulin normally and therefore cannot control the amount of sugar in the blood. 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). 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 the excretion of glucose from the body.

Glitazones 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).

Glitazones are administered orally, typically once daily with or without food.

Glitazones work in the following ways:

  • Insulin is a hormone produced by the pancreas which plays a key role in controlling the levels of glucose in the blood.
  • Patients with T2DM cannot make enough insulin or are resistant to the effects of insulin (insulin resistance). As a result, the body cells cannot use enough glucose from the blood leading to high blood glucose levels.
  • Glitazones 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 the cell’s response to the insulin, leading to excretion of glucose from the body.
  • They increase the level of a natural substance “incretins” which help to control blood sugar by increasing insulin release, particularly after a meal.


Glitazones are used as an adjunct to diet and exercise to improve glycemic control in adults with T2DM. They are used as monotherapy (single drug therapy) or with insulin or other diabetic medications.


Some of the common side effects include:

  • Diarrhea
  • Nausea
  • Vomiting
  • Stomach upset
  • Sore throat
  • Muscle pain
  • Headache
  • Loss of appetite
  • Back pain
  • Bloating
  • Weakness

Other rare side effects include:

  • Upper respiratory tract infection
  • Lower limb edema
  • Weight gain
  • Dizziness (feeling faint, weak, or unsteady)
  • Sinusitis (inflammation or swelling of the tissue lining the sinuses)
  • Pharyngitis (inflammation of the pharynx, which is in the back of the throat) 
  • Anemia (low number of red blood cells)
  • Increased fracture risk
  • Liver toxicity
  • Hypoglycemia (low blood sugar level)
  • Signs of kidney problems 
    • Change in the amount of 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 thiazolidinediones include:

References condition.htm#what_are_side_effects_associated_with_using_pioglitazone

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