1. Metformin/pioglitazone oral tablet is available as brand-name drugs and as a generic drug. Brand names: Actoplus Met, Actoplus Met XR.
  2. Metformin/pioglitazone comes in two forms: oral immediate-release tablet and oral extended-release tablet.
  3. Metformin/pioglitazone is used to lower blood sugar levels in type 2 diabetes. It’s used along with diet and exercise.

FDA warnings

  • This drug has black box warnings. These are the most serious warnings from the Food and Drug Administration (FDA). A black box warning alerts doctors and patients about drug effects that may be dangerous.
  • Heart failure warning: Pioglitazone can cause heart failure or make existing heart problems worse. You shouldn’t use this drug if you have symptoms of heart failure. Symptoms can include fast weight gain and shortness of breath or trouble breathing, especially when you lie down. They can also include unusual tiredness and swelling or fluid retention in your arms or legs.
  • Lactic acidosis warning: Lactic acidosis is a rare but serious side effect of metformin. With this condition, lactic acid builds up in your blood. This is a medical emergency that requires treatment in the hospital. Lactic acidosis is fatal in about half of people who develop it. If you have symptoms of lactic acidosis, you should stop taking this drug and call your doctor right away or go to the emergency room. Symptoms can include weakness, unusual muscle pain, trouble breathing, or unusual sleepiness. They can also include stomach pain, nausea or vomiting, dizziness or lightheadedness, or irregular heart rate.
  • Your risk of lactic acidosis may be higher if you drink a lot of alcohol or take topiramate. It may also be higher if you have kidney disease, sepsis, dehydration, liver problems, or congestive heart failure.

Other warnings

  • Pregnancy risk warning: Pioglitazone may cause women to ovulate (release an egg from an ovary), which can lead to pregnancy. You may ovulate even if you don’t have regular menstrual periods. Ask your doctor about effective forms of birth control to use while you’re taking this medication.
  • X-ray warning: You’ll need to stop taking this drug for a short time if you plan to have an injection of dye or contrast for an x-ray procedure. Taking this drug with x-ray contrast can affect how your kidneys work and increase your risk of lactic acidosis.

Metformin/pioglitazone is a prescription drug. It comes in two forms: oral immediate-release tablet and oral extended-release tablet.

Metformin/pioglitazone oral tablet is available as the brand-name drugs Actoplus Met (immediate-release) and Actoplus Met XR (extended-release). The immediate-release tablet is also available as a generic drug. Generic drugs usually cost less than brand-name versions. In some cases, they may not be available in every strength or form as the brand-name drugs.

Metformin/pioglitazone is a combination of two drugs in a single form. It’s important to know about all the drugs in the combination because each drug may affect you in a different way.

Metformin/pioglitazone may be used as part of a combination therapy. That means you need to take it with other drugs.

Why it's used

Metformin/pioglitazone is used to improve blood sugar control in adults with type 2 diabetes. It’s used along with diet and exercise.

Metformin/pioglitazone isn’t used to treat type 1 diabetes. Also, it isn’t used to treat diabetic ketoacidosis, a complication of diabetes that occurs when your body produces high levels of blood acids called ketones.

How it works

Metformin/pioglitazone is a combination of two diabetes medications that work in different ways.

A class of drugs is a group of medications that work in a similar way. These drugs are often used to treat similar conditions. Metformin belongs to a class of drugs called biguanides.

Metformin reduces the amount of glucose (sugar) made by your liver, lowers the amount of glucose your body absorbs, and increases the effect of insulin on your body. Insulin is a hormone that helps your body remove extra sugar from your blood. This lowers your blood sugar levels.

Pioglitazone belongs to a class of drugs called thiazolidinediones. It works by helping you respond better to the insulin that your body makes. It helps insulin take the glucose from your bloodstream and move it into the cells, where it’s used to make fuel or energy. This lowers your blood sugar levels.

Metformin/pioglitazone oral tablet doesn’t cause drowsiness. However, it may cause a low blood sugar reaction and other side effects.

More common side effects

The more common side effects that occur with metformin/pioglitazone include:

  • diarrhea
  • nausea
  • upset stomach
  • cold-like symptoms (upper respiratory tract infection)
  • swelling in your legs, ankles, or feet (edema)
  • headache
  • weight gain

If these effects are mild, they may go away within a few days or a couple of weeks. If they’re more severe or don’t go away, talk to your doctor or pharmacist.

Serious side effects

Call your doctor right away if you have serious side effects. Call 911 if your symptoms feel life-threatening or if you think you’re having a medical emergency. Serious side effects and their symptoms can include the following:

  • Low blood sugar (hypoglycemia).* Symptoms can include:
    • mood changes, such as irritability, anger, or sadness
    • confusion
    • lightheadedness
    • dizziness
    • sleepiness
    • blurred vision
    • tingling or numbness in your lips or tongue
    • headaches
    • weakness
    • tiredness
    • lack of coordination
    • nightmares or crying out during your sleep
    • seizures
    • loss of consciousness
  • Lactic acidosis. Symptoms can include:
    • weakness or tiredness
    • unusual muscle pain
    • stomach pains, nausea, or vomiting
    • trouble breathing
    • dizziness or lightheadedness
    • slow or irregular heart rate
  • Heart failure. Symptoms can include:
    • swelling or fluid retention, especially in your ankles or legs
    • shortness of breath or trouble breathing, especially when you lie down
    • unusually fast weight gain
    • unusual tiredness
  • Macular edema (swelling in the back of your eye). Symptoms can include:
    • blurred vision
  • Anemia (low red blood cell count). Symptoms can include:
    • pale skin
    • shortness of breath
    • tiredness
    • chest pain
  • Bladder cancer. Symptoms can include:
    • blood in your urine
    • needing to urinate more often than normal
    • pain in your bladder when you urinate
  • Broken bones (fractures)
  • Ovulation, which may lead to pregnancy

Treating low blood sugar

*If you have a low blood sugar reaction, you need to treat it.

  • For mild hypoglycemia (55–70 mg/dL), treatment is 15–20 grams of glucose (a type of sugar). You need to eat or drink one of the following:
    • 3–4 glucose tablets
    • a tube of glucose gel
    • ½ cup of juice or regular, non-diet soda
    • 1 cup of nonfat or 1% cow’s milk
    • 1 tablespoon of sugar, honey, or corn syrup
    • 8–10 pieces of hard candy, such as lifesavers
  • Test your blood sugar 15 minutes after you treat the low sugar reaction. If your blood sugar is still low, repeat the above treatment.
  • Once your blood sugar is back in the normal range, eat a small snack if your next planned meal or snack is more than 1 hour later.

If you don’t treat low blood sugar, you can have a seizure, pass out, and possibly develop brain damage. Low blood sugar can even be fatal. If you pass out because of a low sugar reaction or cannot swallow, someone will have to give you an injection of glucagon to treat the low sugar reaction. You may need to go to the emergency room.

Disclaimer: Our goal is to provide you with the most relevant and current information. However, because drugs affect each person differently, we cannot guarantee that this information includes all possible side effects. This information is not a substitute for medical advice. Always discuss possible side effects with a healthcare provider who knows your medical history.

Metformin/pioglitazone oral tablet can interact with other medications, vitamins, or herbs you may be taking. An interaction is when a substance changes the way a drug works. This can be harmful or prevent the drug from working well.

To help avoid interactions, your doctor should manage all of your medications carefully. Be sure to tell your doctor about all medications, vitamins, or herbs you’re taking. To find out how this drug might interact with something else you’re taking, talk to your doctor or pharmacist.

Examples of drugs that can cause interactions with metformin/pioglitazone are listed below.

Seizure drugs

Taking these drugs with metformin/pioglitazone may raise your risk of lactic acidosis. Examples of these drugs include:

  • topiramate
  • zonisamide
  • acetazolamide

Intravenous (IV) dyes

Having contrast or dye injected into your body while taking metformin/pioglitazone may raise your risk of lactic acidosis. These dyes are used during certain imaging studies such as x-rays.

Drugs for high triglycerides

Taking these medications with metformin/pioglitazone may cause low blood sugar.

Examples of these drugs include:

  • gemfibrozil

Diuretics (water pills)

Taking certain diuretics with metformin/pioglitazone may cause low blood sugar. Examples of these drugs include:

  • amiloride
  • furosemide
  • triamterene

Taking other diuretics with metformin/pioglitazone may cause high blood sugar. Examples of these drugs include:

  • chlorothiazide
  • chlorthalidone
  • hydrochlorothiazide
  • indapamide
  • metolazone

Heart and blood pressure drugs

Taking these drugs with metformin/pioglitazone may cause high blood sugar. Examples of these drugs include calcium channel blockers, such as:

  • amlodipine
  • diltiazem
  • felodipine
  • isradipine
  • nicardipine
  • nifedipine
  • nisoldipine
  • verapamil

Taking other heart drugs with metformin/pioglitazone may cause low blood sugar. Examples of these drugs include:

  • digoxin

Other heart and high blood pressure drugs may either increase or decrease the effect of metformin/pioglitazone. This means that you may have more side effects or the drug won’t work to treat your diabetes. Examples of these drugs include:

  • clonidine
  • reserpine
  • beta blockers, such as:
    • acebutolol
    • atenolol
    • bisoprolol
    • carteolol
    • esmolol
    • metoprolol
    • nadolol
    • nebivolol
    • propranolol

Heart rhythm problem drugs

Taking these drugs with metformin/pioglitazone may cause low blood sugar. Examples of these drugs include:

  • dofetilide

Antibiotics

Taking certain antibiotics with metformin/pioglitazone may cause high blood sugar. Examples of these drugs include:

  • rifabutin
  • rifampin
  • rifapentine
  • rifaximin

Heartburn drugs

Taking these drugs with metformin/pioglitazone may cause low blood sugar. Examples of these drugs include histamine H2 blockers, such as:

  • cimetidine

Diabetes drugs

Taking these drugs with metformin/pioglitazone may cause low blood sugar. Examples of these drugs include:

  • other oral diabetes drugs
  • insulin

Oral steroids

Taking these drugs with metformin/pioglitazone may cause high blood sugar. Examples of these drugs include:

  • dexamethasone
  • hydrocortisone
  • methylprednisolone
  • prednisone
  • prednisolone

Anti-psychotic and anti-nausea drugs

Taking these drugs with metformin/pioglitazone may cause high blood sugar. Examples of these drugs include:

  • chlorpromazine
  • fluphenazine
  • perphenazine
  • prochlorperazine
  • thioridazine

Thyroid drug

Taking levothyroxine with metformin/pioglitazone may cause high blood sugar.

Estrogens

Taking these drugs with metformin/pioglitazone may cause high blood sugar. Examples of these drugs include:

  • conjugated estrogens
  • estradiol

Oral birth control pills

Taking these drugs with metformin/pioglitazone may cause high blood sugar.

Seizure drugs

Taking these drugs with metformin/pioglitazone may cause high blood sugar. Examples of these drugs include:

  • fosphenytoin
  • phenytoin

Tuberculosis (TB) drugs

Taking certain TB drugs with metformin/pioglitazone may cause high blood sugar. Examples of these drugs include:

  • isoniazid

Disclaimer: Our goal is to provide you with the most relevant and current information. However, because drugs interact differently in each person, we cannot guarantee that this information includes all possible interactions. This information is not a substitute for medical advice. Always speak with your healthcare provider about possible interactions with all prescription drugs, vitamins, herbs and supplements, and over-the-counter drugs that you are taking.

This drug comes with several warnings.

Allergy warning

Metformin/pioglitazone can cause a severe allergic reaction. Symptoms include:

  • trouble breathing
  • swelling of your throat or tongue
  • hives

If you develop these symptoms, call 911 or go to the nearest emergency room.

Don’t take this drug again if you’ve ever had an allergic reaction to it. Taking it again could be fatal (cause death).

Alcohol interaction warning

The use of drinks that contain alcohol can increase your risk of lactic acidosis from metformin/pioglitazone. Alcohol may also raise or lower your blood sugar levels. If you drink alcohol, talk to your doctor.

Warnings for people with certain health conditions

For people with diabetic eye disease: If you have macular edema (swelling in the back of your eye), you shouldn’t take this drug. It may make your condition worse.

For people with bladder cancer: This drug may increase the risk of bladder cancer. If you have bladder cancer, you shouldn’t use this drug. If you have a history of the disease, talk to your doctor about whether this drug is safe for you.

For people with heart failure and swelling (edema): This drug can cause your body to retain extra fluid. This leads to swelling and weight gain, and may worsen your heart problems or lead to heart failure. Don’t take metformin/pioglitazone if you have severe heart failure. Your doctor will monitor you for signs of heart failure while you take this drug.

For people with liver disease: Liver disease may put you at a higher risk of lactic acidosis, and pioglitazone may cause liver failure in some people. You shouldn’t use this drug if you have liver disease.

For people with kidney disease: Metformin is removed from your body by your kidneys. If your kidneys don’t work as well as they should, this drug can build up in your body and cause more side effects. This drug should only be used if you have normal kidney function. Your kidney function will be monitored by your doctor.

For people with bone fractures: Pioglitazone can lead to fractures or broken bones, especially in women. Your doctor may recommend other treatments to help your bone health.

For people with anemia: Pioglitazone may cause anemia. Metformin may decrease your vitamin B12 levels and cause anemia as well. Your doctor may do blood tests to check if this drug is safe for you to take.

For people with type 1 diabetes: You shouldn’t use metformin/pioglitazone if you have type 1 diabetes or diabetic ketoacidosis. These conditions should be treated with insulin instead.

Warnings for other groups

For pregnant women: Metformin/pioglitazone has not been studied enough in humans to be certain how the drug might affect the fetus.

Talk to your doctor if you’re pregnant or planning to become pregnant. This drug should only be used if the potential benefit justifies the potential risk to the fetus.

If you become pregnant while taking this drug, call your doctor right away.

For women who are breastfeeding: It isn’t known if metformin/pioglitazone passes into breast milk. If it does, it may cause side effects in a child who is breastfed. Talk to your doctor if you breastfeed your child. You may need to decide whether to stop breastfeeding or stop taking this medication.

For seniors: As you age, your kidneys don’t work as well as they once did. Metformin is removed from your body by your kidneys. If your kidneys don’t work as well as they should, this drug can build up in your body and cause more side effects. This drug should only be used if you have normal kidney function. Your kidney function will be monitored by your doctor.

For children: It isn’t known if metformin/pioglitazone is safe and effective in people younger than 18 years. This drug shouldn’t be used in children.

When to call the doctor

  • Call your doctor if you get sick or injured, have an infection, or plan to have surgery. Metformin/pioglitazone may not control your blood sugar levels during these times. Your doctor may stop this drug for a short time and give you insulin instead.
  • If your dose of metformin/pioglitazone isn’t working well, your diabetes won’t be under control. You will have signs of hyperglycemia (high blood sugar). Call your doctor if you have any of the following symptoms: urinating more often than usual, extreme thirst, extreme hunger, extreme fatigue, blurry vision, cuts or bruises that are slow to heal, tingling, pain, or numbness in your hands or feet.

All possible dosages and forms may not be included here. Your dose, form, and how often you take it will depend on:

  • your age
  • the condition being treated
  • how severe your condition is
  • other medical conditions you have
  • how you react to the first dose

Drug forms and strengths

Generic: Metformin/pioglitazone

  • Form: oral immediate-release tablet
  • Strengths:
    • 500 mg metformin/15 mg pioglitazone
    • 850 mg metformin/15 mg pioglitazone

Brand: Actoplus Met

  • Form: oral immediate-release tablet
  • Strengths:
    • 500 mg metformin/15 mg pioglitazone
    • 850 mg metformin/15 mg pioglitazone

Brand: Actoplus Met XR

  • Form: oral extended-release tablet
  • Strengths:
    • 1,000 mg metformin/15 mg pioglitazone
    • 1,000 mg metformin/30 mg pioglitazone

Dosage for type 2 diabetes

Adult dosage (ages 18–64 years)

Immediate-release tablet

  • People with diabetes not controlled on diet and exercise alone:
    • The typical starting dosage is 500 mg metformin/15 mg pioglitazone taken twice per day with meals, or 850 mg metformin/15 mg pioglitazone taken once per day with meals.
  • People with diabetes not controlled on metformin alone:
    • The typical starting dosage is 500 mg metformin/15 mg pioglitazone taken twice daily with meals, or 850 mg metformin/15 mg pioglitazone once or twice daily with meals. Your dosage depends on the dosage of metformin you’re already taking.
  • People with diabetes not controlled on pioglitazone alone:
    • The typical starting dosage is 500 mg metformin/15 mg pioglitazone taken twice daily with meals, or 850 mg metformin/15 mg pioglitazone once daily with meals.
  • People switching from combination therapy of metformin and pioglitazone as separate tablets:
    • Use your current dosage of metformin and pioglitazone.
  • Maximum dosage:
    • 2,550 mg metformin/45 mg pioglitazone per day. It’s taken as 850 mg metformin/15 mg pioglitazone three times per day.

Extended-release tablet

  • People with diabetes not controlled on diet and exercise alone:
    • The typical starting dosage is 1,000 mg metformin/15 mg pioglitazone or 1,000 mg metformin/30 mg pioglitazone taken once per day with meals.
  • People with diabetes not controlled on metformin alone:
    • The typical starting dosage is 1,000 mg metformin/15 mg pioglitazone taken twice daily with meals, or 1,000 mg metformin/30 mg pioglitazone taken once per day with meals. Your dosage depends on the dosage of metformin you’re already taking.
  • People with diabetes not controlled on pioglitazone alone:
    • The typical starting dosage is 1,000 mg metformin/15 mg pioglitazone taken twice daily with meals, or 1,000 mg metformin/30 mg pioglitazone taken once per day with meals.
  • People switching from combination therapy of metformin and pioglitazone as separate tablets:
    • Dosages should be as close as possible to the dosages of pioglitazone and metformin you’re already taking.
  • Maximum dosage:
    • 2,000 mg metformin/45 mg pioglitazone per day. It’s taken as one 1,000 mg metformin/15 mg pioglitazone extended-release tablet plus one 1,000 mg metformin/30 mg pioglitazone extended-release tablet once per day.

Child dosage (ages 0–17 years)

This medication hasn’t been studied in children. It shouldn’t be used in people younger than 18 years.

Senior dosage (ages 65 years and older)

As you age, your kidneys and liver may not work as well as they did when you were younger. This means you may be more sensitive to the effects of this medication. Your doctor may reduce your starting dosage and adjust your dosage more gradually.

Metformin/pioglitazone shouldn’t be used in people 80 years and older unless you have normal kidney function.

Disclaimer: Our goal is to provide you with the most relevant and current information. However, because drugs affect each person differently, we cannot guarantee that this list includes all possible dosages. This information is not a substitute for medical advice. Always speak with your doctor or pharmacist about dosages that are right for you.

Metformin/pioglitazone oral tablet is used for long-term treatment. It comes with serious risks if you don't take it as prescribed.

If you don’t take it at all: You may still experience high blood sugar levels. Over time, high blood sugar levels can harm your eyes, kidneys, nerves, or heart. This can lead to heart attack, stroke, blindness, kidney failure and dialysis, and limb amputations.

If you take too much: If you take too much metformin/pioglitazone, you may experience low blood sugar. If you think that you’ve taken too much of this medication or have symptoms of low blood sugar, you need to treat your low blood sugar (see above).

If your symptoms continue to worsen, call your doctor or go to the emergency room right away.

What to do if you miss a dose: If you miss a dose of metformin/pioglitazone, take it as soon as you remember. If it’s just a few hours before the time for your next dose, then only take one dose at that time.

Don’t take two doses to try to make up for a missed dose. This could cause dangerous side effects.

How to tell if the drug is working: Your symptoms of high blood sugar should decrease. You may not urinate as often or be as thirsty or hungry. Your blood sugar readings should be lower.

Keep these considerations in mind if your doctor prescribes metformin-pioglitazone for you.

General

  • Metformin/pioglitazone should be taken with meals. This will reduce your risk of diarrhea, nausea, and upset stomach.
  • This drug is given in divided doses with meals, usually twice per day. You should take this drug at the same time each day to keep your blood sugar levels steady.
  • Don’t cut or crush the tablets.
  • Lancets (needles used to draw blood from your finger) are used to test your blood sugar. Don’t throw out lancets into trash cans or recycling bins, and never flush them down the toilet. Ask your pharmacist for a safe container for disposing of used lancets. If you throw out the container in the trash, label it “do not recycle.” Your community may have a program for disposing of lancets.

Storage

  • Store metformin/pioglitazone at room temperature between 59°F and 86°F (15°C and 30°C).
  • Keep the bottle closed tightly and keep the tablets dry.
  • Don’t freeze this drug.
  • Don’t store this medication in moist or damp areas, such as bathrooms.

Refills

A prescription for this medication is refillable. You should not need a new prescription for this medication to be refilled. Your doctor will write the number of refills authorized on your prescription.

Travel

When traveling with your medication:

  • Always carry your medication with you. When flying, never put it into a checked bag. Keep it in your carry-on bag.
  • Don’t worry about airport x-ray machines. They can’t harm your medication.
  • You may need to show airport staff the pharmacy label for your medication. Always carry the original prescription-labeled container with you.
  • Don’t put this medication in your car’s glove compartment or leave it in the car. Be sure to avoid doing this when the weather is very hot or very cold.

Self-management

You will need to test your blood sugar levels at home using a blood glucose monitor. Your doctor may adjust your dosage of metformin/pioglitazone based on your blood sugar levels.

You’ll need to learn how to do the following:

  • use a blood glucose monitor to test your blood sugar regularly at home
  • recognize the symptoms of high and low blood sugar reactions
  • be able to treat low and high blood sugar reactions

To test your blood sugar levels, you’ll need to purchase the following:

  • blood glucose monitoring machine
  • sterile alcohol wipes
  • lancing device and lancets (a pricking needle used to prick your finger to draw a drop of blood for testing blood sugar)
  • blood sugar test strips
  • needle container for safe disposal of lancets

Clinical monitoring

Before and during your treatment with metformin/pioglitazone, your doctor may check your:

  • Blood sugar levels.
  • Glycosylated hemoglobin (A1C) levels. This test measures your blood sugar control over the last 2–3 months.
  • Liver function. If your liver tests are abnormal, or if you have symptoms of liver damage, your doctor may decide to stop this medication.
  • Kidney function. If your kidney tests are abnormal, your doctor may stop this medication.
  • Blood cell counts. Pioglitazone may cause anemia. Metformin may decrease your vitamin B12 levels and cause anemia as well.
  • Eye exams. Pioglitazone may cause macular edema.

Your diet

Managing type 2 diabetes well includes a healthy diet. You should talk to your doctor about how to change your eating habits. In general, a healthy diet is made up of fruits, vegetables, whole grains, fiber-rich foods, fish, and good fats, such as the fats found in avocados, almonds, and olives.

Availability

Not every pharmacy stocks this drug. When filling your prescription, be sure to call ahead to make sure your pharmacy carries it.

Hidden costs

In addition to the medication, you will need to purchase the following:

  • sterile alcohol wipes
  • lancing device and lancets (a pricking needle used to prick your finger to draw a drop of blood for testing blood sugar)
  • blood sugar test strips
  • blood glucose monitoring machine
  • needle container for safe disposal of lancets

Prior authorization

Many insurance companies require a prior authorization for this drug. This means your doctor will need to get approval from your insurance company before your insurance company will pay for the prescription.

There are other drugs available to treat your condition. Some may be better suited for you than others. Talk to your doctor about other drug options that may work for you.

Disclaimer: Healthline 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 other 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.