What Are The Side Effects Of Pioglitazone?

Like all medications, Pioglitazone can have potential side effects, which might leave you questioning whether the benefits outweigh the potential risks. 

It’s beneficial to be aware of a medication’s possible side effects so you know what to watch out for when taking a new medication and when to seek medical attention for more serious side effects.

In this article, we’ll review the side effects of pioglitazone, a medication used to treat type 2 diabetes.

What is pioglitazone (Actos)?

Pioglitazone (drug name Actos) is a drug in a class of medications called thiazolidinediones (TZDs). 

Thiazolidinediones work to lower blood sugar levels by increasing your body’s sensitivity to insulin, the hormone that helps lower blood glucose levels. 

Some of the ways that pioglitazone improves insulin sensitivity are by improving your metabolism of glucose and lipids (fat) and reducing inflammation. 

Insulin resistance (when your body isn’t sensitive to insulin) is the primary cause of type 2 diabetes, which is by far the most prevalent type of diabetes worldwide.

The United States Food and Drug Administration (FDA) approved Pioglitazone in 1999 as a treatment for type 2 diabetes. It isn’t meant to treat type 1 diabetes. 

The usual dose of pioglitazone is 15-30 milligrams with a meal once daily, with a typical maximum daily dose of 45 milligrams.

Rosiglitazone and troglitazone are other types of TZDs that have been discontinued or are rarely used. 

Troglitazone was removed from the market due to severe side effects like fatal liver issues. Rosiglitazone isn’t commonly prescribed anymore due to previous safety concerns that it can cause heart attacks. 

Rosiglitazone use was restricted, but it is still on the market with an updated warning regarding heart failure and other cardiovascular risks.

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What are the side effects of pioglitazone?

The potential side effects of pioglitazone are one of the many reasons that TZDs are not as commonly used anymore. 

You and your healthcare provider should discuss the potential risks of taking pioglitazone to decide if it’s a safe choice for you.

Remember that uncontrolled diabetes comes with several health risks as well, so it’s all about weighing the risks and benefits of your options.

Common side effects

Some of the more common side effects of pioglitazone include:

  • Chest pain
  • Decreased urine output
  • Dilated neck veins
  • Extreme fatigue
  • Irregular breathing
  • Irregular heartbeat
  • Problems with your teeth
  • Swelling of your face, fingers, feet, or lower legs
  • Tightness in your chest
  • Trouble breathing
  • Weight gain

Rare and severe side effects

Liver problems

Pioglitazone is associated with rare cases of acute liver injury, some of which have been fatal. 

One of the major signs of liver problems is jaundice, which is the yellowing of the whites of your eyes and skin. 

Heart failure

Rapid weight gain with swelling of your limbs and/or stomach can be a sign of heart failure, a rare but serious potential side effect of pioglitazone. 

Heart failure from taking pioglitazone is known to occur in patients with underlying heart disease, but the incidence of heart failure from pioglitazone in patients without a history of heart disease isn’t well-documented.

Bladder cancer

The use of pioglitazone has been associated with an increased risk of bladder cancer. If you have bloody urine with urinary urgency, it can be a sign of bladder cancer. 

In 2016, the FDA issued a safety update concluding that pioglitazone can increase bladder cancer risk.

Other signs of bladder cancer can include:

  • Blood or blood clots in your urine
  • Pain or burning sensation during urination
  • Frequent urination
  • Feeling the need to urinate many times throughout the night
  • Feeling the need to urinate but not being able to pass urine
  • Lower back pain on one side of your body

Macular edema

Patients taking pioglitazone are estimated to be 3-6 times more likely to experience macular edema, which is when blood vessels leak into a part of your retina called the macula. 

This results in blurry vision and is common among patients with diabetic retinopathy.

Some signs of macular edema include:

  • Objects look wavy, especially when you look straight ahead
  • Objects look like they’re different sizes if you look out of one eye and then the other
  • Colors look dull or faded

Are there any long-term side effects of taking pioglitazone?

If you develop one of the rare side effects of pioglitazone like bladder cancer, heart failure, or liver problems, the results could be long-term. 

Some of the damage from side effects can be resolved over time, but it all depends on the severity of the side effects.

For instance, an acute liver injury is usually short-term and can be resolved with treatment, but bladder cancer might require the use of chemotherapy or surgery, which could have lasting effects.

Likewise, if you develop macular edema and lose some function of your vision, that can be irreversible, leaving you with lifelong vision problems.

How long do the side effects last?

Some of the more minor side effects of pioglitazone might resolve as your body gets used to the medication, but it all depends on the individual. 

In general, side effects from new medications tend to be the most noticeable when you first start taking the medication or when you increase your dose.

You might notice that the side effects of pioglitazone last the entire time you take it or that you have long-lasting side effects from rare complications such as heart failure or liver problems.

If you don’t experience rare side effects, the side effects of pioglitazone will likely dissipate and go away once you stop taking the medication.

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How to reduce the side effects of pioglitazone

Some of the side effects of pioglitazone might be unavoidable. However, you can do your best to help minimize side effects by:

  • Taking the medication as prescribed. Taking more pioglitazone than is prescribed might result in more noticeable side effects and risks.
  • Limiting the sodium (salt) in your diet. Pioglitazone can cause fluid retention and weight gain. Limiting excess salt in your diet can reduce sodium-related fluid retention and might help reduce the severity of the swelling.
  • Making healthy lifestyle changes. Weight gain is a common side effect of pioglitazone. You might be able to offset some of the weight gain from pioglitazone by making healthy lifestyle changes like being more active, cutting back on your sugar intake, or eating fewer meals outside the home, to name a few ideas.

Who should not take pioglitazone?

History of bladder cancer

If you have bladder cancer or a history of bladder cancer, then pioglitazone isn’t a good choice due to its potential to increase bladder cancer risk. 

If you have a history of or current diagnosis of bladder cancer, your healthcare provider can offer other suggestions for diabetes treatment.

Liver problems

Pioglitazone can cause rare but serious liver problems. If you already have documented liver disease, taking pioglitazone might worsen your liver function. 

Your healthcare provider can offer guidance on whether or not pioglitazone is safe for you to take if you have a history of liver issues.

Women who plan to become pregnant

It isn’t recommended to take pioglitazone if you’re pregnant or plan to become pregnant. There isn’t much information on the safety of pioglitazone during pregnancy, and studies on medications during pregnancy can be difficult to complete because of ethical concerns.

If you’re pregnant or planning to become pregnant, there are safer medication options like insulin and metformin to help you control your blood sugar levels.

Women who are breastfeeding

It’s not known how much pioglitazone might be transferred from a nursing mother to a baby, which could potentially cause low blood sugar levels in the baby. For that reason, it isn’t recommended for breastfeeding mothers to take pioglitazone.

Heart failure

Some of the most concerning potential side effects of pioglitazone are related to its effect on your heart function. 

Heart failure is a rare but very serious possible side effect of pioglitazone, so you shouldn’t take it if you already have a history of heart failure.

In addition, pioglitazone also causes fluid retention and weight gain, which can make your heart work harder to pump blood throughout your body. 

High blood pressure

Pioglitazone might worsen high blood pressure if it causes fluid retention. However, high blood pressure isn’t a contraindication for pioglitazone. In fact, some studies associated pioglitazone use with a reduction in blood pressure levels.

Your healthcare provider can offer guidance on whether or not pioglitazone is safe for you to take if you also have high blood pressure. 

You might be encouraged to monitor your blood pressure levels at home if you start taking pioglitazone to ensure it is well-controlled.

Type 1 diabetes/diabetic ketoacidosis

Pioglitazone helps make you more sensitive to insulin, which is great if your body still produces insulin. 

In the case of type 1 diabetes, though, the cells in your pancreas are no longer able to produce insulin. 

The treatment of type 1 diabetes involves injecting insulin; any other type of medication meant for type 2 diabetes won’t be as effective.

Pioglitazone isn’t effective for treating diabetic ketoacidosis (DKA). DKA is a condition that primarily impacts people with type 1 diabetes and occurs when there isn’t enough insulin present and blood sugar levels climb dangerously high.

Eye problems

Having diabetes puts you at risk of complications like diabetic retinopathy, which is when the nerves in your eyes become damaged due to chronic high blood sugar. 

If you already have diabetic retinopathy or other eye problems, pioglitazone might not be recommended for you since it has the potential to cause macular edema, which can worsen vision function.

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Are there any side effects of stopping pioglitazone?

If you stop pioglitazone, any side effects you were previously experiencing will likely begin to dissipate. Otherwise, you might experience signs of high blood sugar if your blood sugar levels were previously well-controlled on pioglitazone. 

Watch out for signs of high blood sugar like:

  • Blurred vision
  • Fatigue (tiredness)
  • Increased thirst and a dry mouth
  • Increase urinary frequency (peeing often)
  • Recurrent infections like thrush, bladder infections, etc.
  • Unintentional weight loss

Conclusion

Pioglitazone (Actos) is an oral medication used to treat type 2 diabetes. It’s in a class of medications called thiazolidinediones (TZDs) which work to lower blood sugar by making your body more sensitive to insulin.

Some of the most common side effects of pioglitazone are related to fluid retention and weight gain. 

More rare but serious possible side effects include liver problems, heart problems, bladder cancer, and eye problems.

You might need to avoid taking pioglitazone if you have a history of heart failure or other heart problems, bladder cancer, or liver disease, are pregnant or plan to become pregnant, are breastfeeding, or have type 1 diabetes and/or DKA.

Explore More

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Sources

  1. Sears DD, Hsiao G, Hsiao A, Yu JG, Courtney CH, Ofrecio JM, Chapman J, Subramaniam S. Mechanisms of human insulin resistance and thiazolidinedione-mediated insulin sensitization. Proc Natl Acad Sci U S A. 2009 Nov.
  2. Lebovitz HE. Thiazolidinediones: the Forgotten Diabetes Medications. Curr Diab Rep. 2019 Nov.

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