Pioglitazone and Metformin: Benefits, Side Effects, Uses

Pioglitazone and metformin are among some of the older medications for treating type 2 diabetes, so they might not get as much attention as some of the newer diabetes drugs on the market.

In this article, we’ll explain how pioglitazone and metformin work, as well as compare them in terms of cost, side effects, effectiveness, and more.

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. 

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.

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

Pioglitazone was approved by the United States Food and Drug Administration (FDA) in 1999 as a treatment for type 2 diabetes.

Like many oral diabetes medications, it isn’t meant to treat type 1 diabetes. The usual dose of pioglitazone is 15-30 milligrams with a meal once daily, and the daily dose doesn’t usually exceed 45 milligrams.

It’s important to note that some other drugs in the TZD drug class aren’t used very often because of safety concerns. 

For instance, 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. 

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What is metformin?

Metformin is one of the most commonly prescribed oral medications to treat type 2 diabetes. 

According to some estimates, in 2020, metformin was the third most commonly prescribed medication in the United States, with over 92 million prescriptions written.

The FDA approved metformin to treat type 2 diabetes in 1995, so it’s one of the older diabetes medications still frequently used today.

Metformin is the generic name most prescribed (brand names include Glumetza, Fortamet, and Glucophage). 

This medication doesn’t cause low blood sugar (hypoglycemia), which is one of its major benefits and why it’s so popular as a first-line treatment for type 2 diabetes.

Metformin is in a drug class called biguanides, which helps reduce the amount of sugar your liver makes while improving insulin sensitivity. There are two types of metformin – regular and extended-release (XR) tablets.

The common dosage for metformin ranges from 500 milligrams to a maximum of 2,550 milligrams per day.

Are pioglitazone and metformin the same?

Pioglitazone and metformin work to lower blood sugar in similar ways, but that doesn’t make them the same.

Pioglitazone and metformin aren’t the same because they are in two different drug classes with different active ingredients. Pioglitazone is a thiazolidinedione (TZD) and metformin is a biguanide. 

Both pioglitazone and metformin help lower blood sugar by improving insulin sensitivity (reducing insulin resistance). 

Metformin helps reduce the amount of sugar your liver releases, and pioglitazone alters the way you metabolize certain nutrients.

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Pioglitazone vs metformin

The following sections compare pioglitazone vs metformin, including effectiveness, benefits, side effects and risks, and cost.



According to a review of 11 studies (6 used pioglitazone as the only type of medication and 5 combined pioglitazone with other diabetes medications), pioglitazone resulted in:

  • Reductions of blood sugar levels up to 95 mg/dL
  • Reductions in hemoglobin A1c (the maximum reduction seen was 2.6%)
  • Weight gain of 4 kilograms (nearly 9 pounds) over 16 weeks


According to studies, metformin is effective at lowering both fasting blood sugar and hemoglobin A1c levels. 

How much metformin lowers your blood sugar seems to be dose-dependent, meaning the more metformin you take, the more it can help lower your blood sugar.

Metformin can lower blood sugar levels in both obese and non-obese patients with type 2 diabetes. 

One study found that hemoglobin A1c levels dropped by a little over 1% in both obese and non-obese patients after 12 months of taking metformin.

Overall, metformin seems to lower A1c levels by around 1%, according to available studies. 

Which medication is more effective?

A study compared pioglitazone vs metformin directly and concluded that both medications are equally as effective at lowering blood sugar levels.


Pioglitazone and metformin differ in their safety for use among different populations, which means one might be preferred over the other if you have certain health issues like heart problems.


The use of pioglitazone isn’t recommended for certain people, including:

  • Having a history of bladder cancer: pioglitazone isn’t a good choice due to its potential to increase bladder cancer risk
  • Liver problems: pioglitazone can cause rare but serious liver problems. If you already have documented liver disease, taking pioglitazone might worsen your liver function.
  • Pregnancy or breastfeeding: the use of pioglitazone isn’t recommended if you’re planning to become pregnant or if you’re breastfeeding. 
  • Heart failure: 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.

    Pioglitazone also causes fluid retention and weight gain, which can make your heart work harder to pump blood throughout your body. 
  • High blood pressure: while some studies suggest improvements in blood pressure levels from pioglitazone, pioglitazone might worsen high blood pressure if it causes fluid retention.

    Pioglitazone use isn’t contraindicated for people with high blood pressure, but you should discuss with your healthcare provider if you have pre-existing high blood pressure (hypertension).
  • Eye problems: if you already have diabetic retinopathy or other eye problems, pioglitazone might not be recommended for you since it might cause macular edema, which can worsen vision function.
  • The use of pioglitazone in people under age 18 isn’t established.


  • Metformin can be used in people as young as ten years old.
  • Metformin is considered safe during pregnancy (category B) and is generally compatible with breastfeeding, though caution should be exercised in premature babies or babies with kidney problems.
  • Like pioglitazone, metformin might be contraindicated in some patients with heart failure, but in general, it seems to be safer than pioglitazone for patients with heart failure.

Here is a summary of the uses for pioglitazone vs metformin:

Intended to treat type 1 diabetesNoNo
Safe for pregnancyNot generallyYes (category B)
Safe for breastfeedingNot generallyYes, in most cases
Used for patients under the age of 18NoYes
Safe for heart failureNoYes, depending on the type; considered safer than pioglitazone for HF
Safe for a history of bladder cancerNoYes
Safe for patients with eye problemsNot usuallyYes. It might help reduce age-related vision loss
Used in patients with liver problemsCan be contraindicated depending on severityGenerally only contraindicated for severe cirrhosis (liver scarring)


Both metformin and pioglitazone have potential benefits related to improving insulin sensitivity and blood sugar levels. 

They also share benefits such as:

  • Being oral medications: pioglitazone and metformin are ideal for patients who don’t want to take injections.
  • Cost-effectiveness: both medications have a generic version which makes them much more affordable compared to some other diabetes drugs.

Metformin seems to have more benefits over pioglitazone regarding safety and usage, as well as the fact that metformin isn’t likely to cause weight gain like pioglitazone can.

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Side effects and risks


Like any medication, some side effects are more common (and generally not severe), while others are less common but can be more severe.

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

TZDs like pioglitazone aren’t as commonly used due to the potential for serious side effects. However, pioglitazone is still considered a reasonable option to treat insulin resistance, especially due to its cost-effectiveness compared to some of the newer diabetes medications on the market.

Some of the potential rare side effects of pioglitazone can include:

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.

This is one of the reasons pioglitazone might not be a good option if you have certain heart problems like heart failure.

Bladder cancer

The use of pioglitazone has been associated with an increased risk of bladder cancer. Some of the signs of bladder cancer include bloody urine with urinary urgency.

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

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Macular edema

Macular edema occurs 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.

Patients taking pioglitazone are estimated to be 3-6 times more likely to experience macular edema, 


The most common metformin side effects tend to be stomach-related and can include:

  • Heartburn
  • Stomach pain
  • Nausea or vomiting
  • Bloating
  • Gas
  • Diarrhea
  • Constipation
  • Weight loss
  • Headache
  • A metallic taste in your mouth

Lactic acidosis

Rarely, taking too much metformin can cause lactic acidosis, an uncommon but serious condition. 

The few documented cases of lactic acidosis from metformin are generally from intentional overdoses with suicidal intent.

The risk of lactic acidosis from taking metformin as prescribed is considered so low that it shouldn’t even be considered when making decisions about which medications should be prescribed to patients with diabetes.

Vitamin B12 deficiency

Metformin can cause vitamin B12 deficiency in some people. If you have signs of B12 deficiency, you should be tested so you can be treated with intramuscular vitamin B12 shots.

Which medication is cheaper?

According to GoodRx, here are some estimated out-of-pocket costs for pioglitazone vs metformin (keep in mind that if you have insurance, these prices could be different):

A month’s supply of 30-milligram tablets of pioglitazone costs around $15 at most major pharmacies

A month’s supply of metformin at a dose of 2,000 milligrams daily (1000 milligrams twice daily) costs around $2-20, with most estimates below $10.

Both medications are equally affordable thanks to the fact that they have generic versions. Some of the newer diabetes drugs are very expensive out-of-pocket because generic versions don’t yet exist.

Can you take Pioglitazone and metformin together?

Yes, pioglitazone and metformin can be taken together. If you’re already taking metformin or pioglitazone separately, you can ask your healthcare provider if taking them together would be advantageous, given your health history and blood sugar trends.


Pioglitazone and metformin are both oral medications used to treat type 2 diabetes. Pioglitazone is in a class of medications called thiazolidinediones, and metformin is in a class called biguanides.

Both drugs work to improve insulin sensitivity but work in different ways. Efficacy appears to be similar for pioglitazone vs. metformin.

Metformin is generally considered safer and can be used among a wider variety of patients, and isn’t likely to cause weight gain like pioglitazone can.

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