How Do Antidiabetic Biguanides Thiazolidinediones Work?

Antidiabetic biguanides/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 of a heart attack or stroke. Glitazones are a combination of two oral antihyperglycemic drugs (metformin and pioglitazone) to control blood sugar in adults with T2DM who do not use daily insulin injections. 

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 available as oral immediate-release tablets and extended-release (long-acting) tablets and are typically taken once or twice daily with or without food.

Glitazones work in the following ways:

• They reduce the production of glucose during digestion by decreasing the amount of glucose absorbed from the food.
• They prevent the liver from converting fats and amino acids into glucose.
• They increase the excretion of sugar by the kidneys.
• They decrease the amount of sugar that the body absorbs through the stomach and intestines.
• They are insulin sensitizers that act on intracellular metabolic pathways to enhance insulin action and increase insulin sensitivity in body tissues.
• They increase adiponectin (a cytokine secreted by fat tissues) that increases insulin sensitivity and fatty acid oxidation, decreases hepatic gluconeogenesis (a process by which glucose is produced in the liver), and increases insulin-dependent glucose uptake in muscles and fat.
• 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.

Glitazones 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
• Sore throat
• Muscle pain
• Headache
• Bloating
• Weakness
• Unpleasant metallic taste in the mouth

Other rare side effects include:

• Lactic acidosis (increased lactic acid in the bloodstream which is produced when oxygen levels become low in cells within the areas of the body where metabolism occurs)
• 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)
• Increased fracture risk
• Liver toxicity
• 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 antidiabetic biguanides/thiazolidinediones include:

• ACTOplus Met
• ACTOplus Met XR
• Avandamet
• Metformin/pioglitazone
• Metformin/rosiglitazone