Thiazolidinediones (TZDs)

Reviewed by: HU Medical Review Board | Last reviewed: August 2023 | Last updated: November 2023

Thiazolidinediones (TZDs) are drugs sometimes used to treat adults with type 2 diabetes (T2D). They control blood sugar levels by improving how your body uses insulin. TZDs should be used along with lifestyle changes, such as diet and exercise.1,2

TZDs are usually not the first treatment for T2D unless other options cannot be used. They are more often used as second-line options when other treatments do not control blood sugar. This is because TZDs can have serious side effects.1,2

How do TZDs work?

TZDs increase your sensitivity to insulin. In other words, TZDs help your body better respond to its natural insulin. This can lower the amount of insulin your body uses to remove glucose (sugar) from the blood. TZDs also lower the amount of glucose made by your liver.1

We do not yet know exactly how TZDs cause these effects. They bind to a certain type of proteins called peroxisome proliferator-activated receptors (PPARs). PPARs regulate how our cells use energy in response to hormones and other cues. TZDs seem to activate PPARs in body fat cells (adipose tissue). This changes how your body stores and processes sugars and fats.1


Two TZDs have been approved by the US Food and Drug Administration (FDA) to treat adults with T2D:2,3

  • Rosiglitazone maleate (Avandia®)
  • Pioglitazone (Actos®)

These 2 TZDs have benefits over other T2D treatments for people who have:2,4

  • A high risk for low blood sugar
  • Severe insulin resistance
  • Nonalcoholic steatohepatitis (NASH)
  • Had a recent stroke
  • Concerns with cost

Pioglitazone is used more often than rosiglitazone. In fact, rosiglitazone is not used often anymore. This is because it has a higher risk of side effects compared to pioglitazone.2

What are the possible side effects?

Side effects can vary depending on the specific TZD you are taking. Some of the most common side effects of TZDs include:1,2

  • Swelling (edema)
  • Headache
  • Weight gain
  • Muscle pain
  • Cold-like symptoms

TZDs can also cause serious, life-threatening side effects. These include:1,2

  • Heart failure
  • Heart attack
  • Liver problems
  • Eye/vision problems
  • Bone fractures
  • Low red blood cell counts (anemia)
  • Low blood sugar (hypoglycemia)
  • Higher risk of bladder cancer

Actos carries a boxed warning, the strictest warning from the FDA. It has this warning because it can cause congestive heart failure or make it worse in some people. For this reason, Actos is not recommended for people with signs of heart failure.6

After beginning Actos and any time a dose increases, your doctor should monitor you closely for signs of heart failure.6

Avandia also carries a boxed warning. It has this warning because it can cause congestive heart failure or make it worse in some people. Studies have shown it also may increase the risk of angina and heart attack.7

Avandia is not recommended for people with signs of heart failure. After beginning Avandia and any time a dose increases, your doctor should monitor you closely for signs of heart failure.7

These are not all the possible side effects of TZDs. Talk to your doctor about what to expect when taking TZDs. You also should call your doctor if you have any changes that concern you when taking TZDs.

Other things to know

Take these drugs exactly as your doctor prescribes. TZDs should be used with lifestyle changes such as diet, exercise, and weight loss.2

Your doctor will perform tests before and during treatment with TZDs. For example, they will monitor your liver function every few months.2

Your doctor may suggest combining TZDs with other medicines, such as metformin or sulfonylureas. Combining TZDs with insulin increases the risk of side effects. It is not common to take TZDs and insulin together.2

Do not take TZDs if you:2,4

  • Have a history of heart failure
  • Have a history of fracture or a high risk of fracture
  • Have active liver disease
  • Have active or history of bladder cancer
  • Are pregnant
  • Are allergic to any ingredients in TZDs

Before beginning treatment for T2D, tell your doctor about all your health conditions and any other drugs, vitamins, or supplements you take. This includes over-the-counter drugs.

For more information, read the full prescribing information for Actos and Avandia.

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