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Medically reviewed by Melissa Badowski, PharmD, MPH, FCCP on May 5, 2023
Written by Alex Brewer, PharmD, MBA

This article describes pioglitazone/glimepiride’s uses, side effects, and more. Below you’ll find some coupon options to help save on the cost of pioglitazone/glimepiride.

Boxed warning: Risk of heart failure

Pioglitazone/glimepiride has a boxed warning about the risk of heart failure. Boxed warnings are serious warnings from the Food and Drug Administration (FDA).

For details, see the “Interactions and warnings for pioglitazone/glimepiride” section below.

Pioglitazone/glimepiride may cause mild or serious side effects (also known as adverse effects). More common mild side effects of pioglitazone/glimepiride and its serious side effects are listed below. This article doesn’t include all possible side effects of the drug. Side effects can vary based on your age, overall health, and any other medications you take.

To learn more about pioglitazone/glimepiride’s side effects, talk with your doctor or pharmacist. You can also read the prescribing information* for pioglitazone/glimepiride.

* To view pioglitazone/glimepiride’s prescribing information, see the “Article resources” section below.

Mild side effects

More common mild side effects reported with pioglitazone/glimepiride are listed below.

This article doesn’t include all possible mild side effects of the drug. To learn more about pioglitazone/glimepiride’s side effects, see the prescribing information* for pioglitazone/glimepiride.

With many drugs, mild side effects may go away within a few days or a couple of weeks. If the side effects are bothersome, tell your doctor or pharmacist. They may be able to suggest ways to manage them.

Pioglitazone/glimepiride oral tablet’s mild side effects include:

• upper respiratory infection, such as the common cold
• headache
• sinus infection
• weight gain
• mild allergic reaction†

* To view pioglitazone/glimepiride’s prescribing information, see the “Article resources” section below.
† For details about this side effect, see the “Interactions and warnings for pioglitazone/glimepiride” section below.

Serious side effects

Serious side effects of pioglitazone/glimepiride are listed below.

This article doesn’t include all possible serious side effects of the drug. To learn more about pioglitazone/glimepiride’s side effects, see the prescribing information* for pioglitazone/glimepiride.

With many drugs, serious side effects are possible but not common. If you have serious side effects from this drug, call your doctor right away. If you’re having severe symptoms or a medical emergency, call 911 or a local emergency number.

In general, pioglitazone/glimepiride’s serious side effects include:

• diabetic macular edema (an eye condition that may result from diabetes)
• increased risk of broken bones
• liver failure
• low blood sugar
• possible increased risk of bladder cancer
• boxed warning: risk of heart failure†
• severe allergic reaction†

* To view pioglitazone/glimepiride’s prescribing information, see the “Article resources” section below.
† For details about this side effect, see the “Interactions and warnings for pioglitazone/glimepiride” section below.

Below you’ll find answers to a few commonly asked questions about pioglitazone/glimepiride.

Can I take pioglitazone/glimepiride with metformin?

Yes, it’s generally considered safe to take pioglitazone/glimepiride with metformin (Fortamet, Glumetza). These medications aren’t known to interact with each other.

That said, metformin and pioglitazone/glimepiride can cause some similar side effects. Examples include low blood sugar and, in rare cases, liver failure. Taking these medications together increases your risk of these side effects. But the benefits of taking the drugs to lower blood sugar may outweigh the risks for some people.

Your doctor or pharmacist can provide more information on the benefits and risks of taking metformin with pioglitazone/glimepiride. They can also determine whether this is a safe combination for you to take.

Is pioglitazone/glimepiride similar to glipizide, glyburide, or vildagliptin?

Yes, in some ways. But these drugs also have some differences.

Pioglitazone/glimepiride, glipizide (Glucotrol XL), glyburide (Glynase), and vildagliptin are all prescribed to manage blood sugar levels in people with type 2 diabetes.

Unlike the other drugs mentioned here, vildagliptin is not approved by the Food and Drug Administration (FDA) for use in the United States.

Glimepiride, glipizide, and glyburide all belong to a group of drugs called sulfonylureas. This means these drugs work in the same way to lower blood sugar levels. Pioglitazone and vildagliptin work differently to treat type 2 diabetes.

Your doctor or pharmacist can provide more information on how pioglitazone/glimepiride compares to other treatments for type 2 diabetes.

Will pioglitazone/glimepiride 30 mg/2 mg cause fewer side effects than the 30 mg/4 mg strength of the drug?

Maybe. In general, lower strengths of a drug are less likely to cause side effects compared with higher strengths. This was true for certain side effects reported in pioglitazone/glimepiride’s studies, such as weight gain and edema.

If you’d like to know more about how your pioglitazone/glimepiride dose affects your risk of side effects, talk with your doctor or pharmacist.

Does pioglitazone/glimepiride cause long-term side effects?

Yes, in some cases, pioglitazone/glimepiride may cause long-term side effects. These can occur if you take the drug for a long time. And some side effects may last for a while after you’ve stopped taking the drug.

Examples of long-term side effects include:

• diabetic macular edema (an eye condition that may result from diabetes)
• liver failure, which may not go away even if you stop treatment
• boxed warning: risk of heart failure*

* For details about this side effect, see the “Interactions and warnings for pioglitazone/glimepiride” section below.

Talk with your doctor to learn more about these side effects and how to best manage them. Ask your doctor for more information about how long these side effects of pioglitazone/glimepiride may last.

How does pioglitazone/glimepiride work? And how long does it take to start working?

Pioglitazone/glimepiride contains two active drugs. An active drug is the ingredient that makes a medication work.

Pioglitazone and glimepiride work differently for managing blood sugar levels in people with type 2 diabetes.

Pioglitazone belongs to a group of drugs called thiazolidinediones. It can lower blood sugar levels by helping the insulin made by your body work better. Insulin is a hormone that helps send sugar out of your blood and into your cells to use as energy.

Glimepiride belongs to a group of drugs called sulfonylureas. It helps lower blood sugar levels by causing your pancreas to release insulin.

Pioglitazone/glimepiride begins working when you take a dose. But it can take a few weeks or months before you notice long-term changes to your blood sugar level. Your doctor can provide more information on how they’ll determine whether the drug helps manage your blood sugar.

If you have additional questions about how pioglitazone/glimepiride works or when you may notice changes in your blood sugar level from taking the drug, ask your doctor or pharmacist.

The Food and Drug Administration (FDA) approves prescription drugs such as pioglitazone/glimepiride for certain conditions. Approved uses for pioglitazone/glimepiride are described below.

Use for type 2 diabetes

Doctors may prescribe pioglitazone/glimepiride oral tablet for managing blood sugar levels in adults with type 2 diabetes. For this purpose, the drug is part of a treatment plan that includes a balanced diet and exercise. It’s typically prescribed as a long-term treatment.

Usually, a person’s body releases the hormone insulin to move glucose (sugar) out of the blood and into cells. The cells use this sugar for energy. With type 2 diabetes, cells stop responding or don’t respond as well to insulin. And the body may stop making insulin or may not make enough. This causes high blood sugar.

Over time, high blood sugar can cause serious harm to the heart, kidneys, eyes, and other parts of the body.

Symptoms of type 2 diabetes include fatigue (low energy), increased thirst or appetite, and urinating more frequently than usual.

Doctors will likely not prescribe pioglitazone/glimepiride oral tablet to treat type 1 diabetes. Also, pioglitazone/glimepiride should not be used to treat diabetic ketoacidosis (DKA), a serious condition that causes the blood to be too acidic.

The dosage of pioglitazone/glimepiride your doctor prescribes may vary based on your condition and certain other factors. Talk with your doctor about the dosage you should take.

Taking pioglitazone/glimepiride

Pioglitazone/glimepiride oral tablet is taken by mouth, with your first main meal of the day.

Your doctor will talk with you about how to take pioglitazone/glimepiride. They’ll explain how much to take and how often. Always follow your doctor’s recommendation.

Overdose of pioglitazone/glimepiride

You should not take more pioglitazone/glimepiride than your doctor prescribes. For some drugs, doing so may lead to serious side effects or overdose.

If you think you’ve taken too much pioglitazone/glimepiride, call your doctor or pharmacist right away. Or you could call 800-222-1222 to speak with someone at America’s Poison Centers. You can also use its online resource. If you have concerning symptoms, call 911 or a local emergency number immediately. You can also go to the closest emergency room.

Below, you’ll find information about pioglitazone/glimepiride’s possible interactions and warnings.

Interactions of pioglitazone/glimepiride

For some medications, certain things may affect how the drug works. These include getting vaccines, consuming alcohol or certain foods, or taking the drug with other medications. This effect is called a drug interaction.

Before you take pioglitazone/glimepiride, ask your doctor to check for possible interactions. Be sure to tell them about any of the following you take or use:

• prescription medications
• over-the-counter medications
• vitamins, herbs, or supplements

To learn about drug-condition interactions, see the “Warnings for pioglitazone/glimepiride” section below.

Warnings for pioglitazone/glimepiride

Pioglitazone/glimepiride should not be taken by certain people, and it should be taken cautiously by certain others.

Boxed warning: Risk of heart failure

Pioglitazone/glimepiride has a boxed warning about the risk of heart failure. Boxed warnings are serious warnings from the Food and Drug Administration (FDA).

With heart failure, your heart has trouble pumping blood properly throughout your body. Though rare, this side effect was reported in studies of pioglitazone/glimepiride.

Symptoms may include:

• fatigue (low energy)
• sudden, unintended weight gain
• shortness of breath

If you experience symptoms of heart failure, tell your doctor. They’ll likely recommend:

• a treatment for your symptoms, including medications for treating heart failure
• reducing your pioglitazone/glimepiride dose or stopping treatment

For people who already have heart failure, taking pioglitazone/glimepiride could worsen their condition. If you have heart failure, your doctor will determine whether this drug is safe for you to take.

To learn more, talk with your doctor or pharmacist.

Other warnings

Pioglitazone/glimepiride could cause harm to people with certain health conditions. This effect is called a drug-condition interaction. Other factors can also affect whether pioglitazone/glimepiride is a safe option for you.

Ask your doctor about specific warnings for pioglitazone/glimepiride, and be sure to tell your doctor about your:

• current health, including any allergies to medications
• past health conditions or surgeries

Allergic reaction

Pioglitazone/glimepiride can cause an allergic reaction in some people. Severe allergic reactions are rare but possible.

If you’ve had an allergic reaction to pioglitazone/glimepiride or any of its ingredients, your doctor will likely not prescribe pioglitazone/glimepiride. They can tell you about medications that are safer options for you.

A mild allergic reaction may cause the following symptoms:

• skin rash
• itchiness
• flushing (temporary warmth, redness, or deepening of skin color)

A severe allergic reaction may cause the following symptoms:

• swelling under your skin, usually in your hands, feet, eyelids, or lips
• swelling of your mouth, throat, or tongue, which can cause breathing problems

If you have an allergic reaction to pioglitazone/glimepiride, call your doctor right away. If you have severe symptoms, call 911 or a local emergency number.

Pregnancy or breastfeeding and pioglitazone/glimepiride

Information about pioglitazone/glimepiride and pregnancy and breastfeeding is described below.

Pioglitazone/glimepiride and pregnancy

There are risks to taking pioglitazone/glimepiride during pregnancy. But there are also risks with having untreated type 2 diabetes while pregnant. (Keep in mind that pioglitazone/glimepiride is used for treating type 2 diabetes.)

If you’re planning a pregnancy or can become pregnant, talk with your doctor about type 2 diabetes treatment options during pregnancy. Together, you can discuss the risks and benefits of your treatment options and decide whether you should take pioglitazone/glimepiride during pregnancy.

Pioglitazone/glimepiride and breastfeeding

It’s not known whether pioglitazone/glimepiride should be taken while breastfeeding. If you’re currently breastfeeding or planning to do so, talk with your doctor before taking this medication.

You may be able to save money on your prescription for pioglitazone/glimepiride by using our Perks discount coupons. They can be found at the end of this article.

If you have questions about how to pay for pioglitazone/glimepiride, talk with your doctor or pharmacist. You can also learn more about the cost of pioglitazone/glimepiride in this article.

Note: Optum Perks coupons cannot be used with insurance copays or benefits.

This article describes pioglitazone/glimepiride’s uses and side effects, ways to save on cost, and more. Let your doctor know if you have questions about pioglitazone/glimepiride or would like more details about it.

Here’s a list of some possible questions you may want to ask your doctor:

• How does pioglitazone/glimepiride compare to other treatments for type 2 diabetes?
• Are my risks of side effects from taking pioglitazone/glimepiride different from those of taking the drugs as separate pills?
• If I have side effects from pioglitazone/glimepiride, can you prescribe a lower dose for me to try?
• How will you monitor whether pioglitazone/glimepiride is working for me? Will I need to have lab tests and blood draws?

• Food and Drug Administration. (2023). Orange Book: Approved drug products with therapeutic equivalence evaluations. https://www.accessdata.fda.gov/scripts/cder/ob/index.cfm
• Pioglitazone and glimepiride- pioglitazone and glimepiride tablet. (2017). https://nctr-crs.fda.gov/fdalabel/services/spl/set-ids/ea385b3d-cb4c-4550-97b0-93a86533f6dc/spl-doc

Disclaimer: Optum Perks has made every effort to make certain that all information is factually correct, comprehensive, and up to date. However, this article should not be used as a substitute for the knowledge and expertise of a licensed healthcare professional. You should always consult your doctor or another healthcare professional before taking any medication. The drug information contained herein is subject to change and is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. The absence of warnings or other information for a given drug does not indicate that the drug or drug combination is safe, effective, or appropriate for all patients or all specific uses.