What are the potential side effects of Actos. How does Actos work to lower blood sugar. Why have some countries banned or restricted Actos use. What should patients discuss with their doctor before starting Actos treatment. How has Actos been linked to increased bladder cancer risk.

What is Actos and How Does it Work?

Actos (pioglitazone) is a medication used to treat type 2 diabetes. It belongs to a class of drugs called thiazolidinediones (TZDs). Actos works by:

• Increasing the body’s sensitivity to insulin
• Reducing the amount of glucose released by the liver
• Helping the body remove excess blood sugar more effectively

The Food and Drug Administration (FDA) approved Actos in 1999. It is manufactured by Takeda Pharmaceuticals America Inc., which also produces combination versions of the drug:

• Actoplus Met and Actoplus Met XR (pioglitazone + metformin)
• Duetact (pioglitazone + glimepiride)
• Oseni (pioglitazone + alogliptin)

For a time, Actos was one of the most successful diabetes medications globally. In 2007, it became the world’s best-selling diabetes drug after studies linked its rival, Avandia, to a higher risk of heart attack. Before its patent expired in 2011, Actos generated $3.58 billion in U.S. sales in 2010, accounting for 27% of Takeda’s revenue.

Actos Dosage and Administration Guidelines

How should Actos be taken? The medication comes in tablet form and is typically prescribed as follows:

• Taken once daily, with or without food
• Starting dose usually 15 mg or 30 mg
• Dose can be increased by 15 mg increments up to a maximum of 45 mg daily

Is a lower dose of Actos preferable? A 2022 study suggested that lower doses of pioglitazone may offer similar benefits with fewer adverse effects compared to the maximum recommended dose. The research found that for edema, weight gain, and heart failure, risk estimates were lower for subjects taking less than 45 mg daily.

It’s crucial to follow your doctor’s instructions precisely when taking Actos. Do not alter your dose without consulting your healthcare provider. Inform your doctor of any significant changes in your health status, such as accidents, surgeries, fevers, or infections, as these may necessitate dosage adjustments.

Monitoring Your Progress on Actos

While taking Actos, it’s important to:

• Continue following your prescribed diet and exercise regimen
• Regularly test your blood sugar levels
• Undergo hemoglobin A1C tests to assess the medication’s effectiveness
• Have regular eye examinations to check for fluid buildup that could affect vision

Safety Concerns and FDA Warnings for Actos

Despite its effectiveness in managing type 2 diabetes, Actos has been associated with several safety concerns and FDA warnings. What are the main issues surrounding Actos use?

Increased Risk of Bladder Cancer

Multiple studies and an FDA review have linked higher dosages and prolonged use of Actos to an increased risk of bladder cancer. This association has led to significant legal and regulatory actions:

• In 2011, health regulators in Germany and France ordered Takeda to remove Actos from the market
• The Indian government also banned the drug
• Takeda set aside $2.7 billion in 2015 to cover the costs of settling Actos lawsuits related to bladder cancer and other injuries

Despite these actions, Actos remains available by prescription in the United States, though the FDA continues to monitor its safety profile.

Heart Failure and Other Cardiovascular Concerns

Actos may exacerbate or increase the risk of heart failure in some patients. This risk appears to be dose-dependent, with higher doses potentially posing a greater threat. Patients with a history of heart problems should be closely monitored while taking Actos.

Liver Problems

Actos can affect liver function. Before prescribing the medication, doctors typically order liver function tests. Patients with existing liver issues should be carefully monitored for any signs of worsening condition while on Actos.

Who Should Not Take Actos?

Certain individuals should not use Actos or should use it with caution. Who falls into these categories?

• Children under 18 years old
• Patients with Type 1 diabetes
• Those who have experienced diabetic ketoacidosis
• Individuals with active bladder cancer or a history of bladder cancer
• Patients with severe heart failure
• Those with significant liver problems

Pregnant women or those planning to become pregnant should also exercise caution, as Actos can harm unborn babies and may increase fertility in some individuals. The medication also passes into breast milk, potentially affecting nursing infants.

Common Side Effects of Actos

While Actos can be effective in managing type 2 diabetes, it may cause various side effects. What are some of the most common adverse reactions to Actos?

• Weight gain
• Edema (fluid retention)
• Upper respiratory tract infections
• Headache
• Muscle pain
• Sinus inflammation
• Dizziness

These side effects are generally mild to moderate in severity. However, if they persist or worsen, it’s important to consult your healthcare provider.

Weight Gain and Fluid Retention

Weight gain is a common side effect of Actos, often due to fluid retention. This can be particularly problematic for patients with heart conditions, as it may increase the risk of heart failure. How much weight gain can be expected with Actos use?

Studies have shown that patients taking Actos may experience an average weight gain of 2-6 pounds over the first 6-12 months of treatment. This weight gain tends to plateau after the first year of use.

Serious Side Effects and Complications of Actos

While less common, Actos can potentially cause more serious side effects. What are some of the severe complications associated with Actos use?

Bladder Cancer

As mentioned earlier, long-term use of Actos, particularly at higher doses, has been linked to an increased risk of bladder cancer. Patients taking Actos should be vigilant for symptoms such as:

• Blood in urine
• Urgent need to urinate
• Pain during urination
• Lower back or abdominal pain

Bone Fractures

Actos may increase the risk of bone fractures, particularly in women. This risk appears to be higher for fractures of the upper arm, hand, and foot. How does Actos affect bone health?

The medication may decrease bone density over time, making bones more fragile and susceptible to fractures. Patients, especially postmenopausal women, should discuss this risk with their healthcare provider and consider strategies to maintain bone health while on Actos.

Macular Edema

Actos can cause or worsen macular edema, a condition characterized by swelling in the back of the eye that can affect vision. Patients with diabetes are already at increased risk for eye problems, and Actos may exacerbate this risk.

Regular eye exams are crucial for patients taking Actos. What symptoms should prompt immediate medical attention?

• Blurred vision
• Changes in color perception
• Decreased visual acuity

Drug Interactions and Precautions

Actos can interact with various medications and substances, potentially altering its effectiveness or increasing the risk of side effects. What are some important drug interactions to be aware of when taking Actos?

Insulin and Other Diabetes Medications

Combining Actos with insulin or other diabetes drugs can increase the risk of hypoglycemia (low blood sugar). Careful monitoring of blood glucose levels is essential when using these medications together.

CYP2C8 Inhibitors

Medications that inhibit the CYP2C8 enzyme, such as gemfibrozil, can increase the concentration of Actos in the body, potentially enhancing both its effects and side effects. Dose adjustments may be necessary when using these drugs concurrently.

Oral Contraceptives

Actos may reduce the effectiveness of oral contraceptives. Women taking both medications should consider additional forms of birth control.

It’s crucial to inform your healthcare provider about all medications, supplements, and herbal products you’re taking to avoid potential interactions with Actos.

Monitoring and Management Strategies for Actos Patients

Given the potential risks associated with Actos, proper monitoring and management are essential for patients using this medication. What strategies can help ensure safe and effective use of Actos?

Regular Health Check-ups

Patients taking Actos should undergo regular health assessments, including:

• Liver function tests
• Hemoglobin A1C measurements
• Cardiovascular evaluations
• Eye examinations
• Bone density scans (especially for postmenopausal women)

Blood Sugar Monitoring

Frequent blood glucose testing is crucial for patients on Actos. This helps ensure the medication is effectively controlling blood sugar levels and allows for timely adjustments to the treatment plan if needed.

Lifestyle Modifications

While Actos can help manage blood sugar, it’s most effective when combined with lifestyle changes. What lifestyle modifications can enhance the effectiveness of Actos treatment?

• Following a balanced, diabetes-friendly diet
• Engaging in regular physical activity
• Maintaining a healthy weight
• Quitting smoking
• Limiting alcohol consumption

These lifestyle changes not only improve the effectiveness of Actos but also contribute to overall health and may help mitigate some of the medication’s potential side effects.

Patient Education

Educating patients about the potential risks and benefits of Actos is crucial. Patients should be aware of the signs and symptoms that require immediate medical attention, such as:

• Unexplained weight gain or swelling
• Shortness of breath or difficulty breathing
• Unusual tiredness
• Dark urine or yellowing of the skin or eyes
• Vision changes
• Signs of bladder cancer (as mentioned earlier)

By understanding these potential complications, patients can play an active role in monitoring their health while taking Actos.

Alternatives to Actos for Type 2 Diabetes Management

Given the potential risks associated with Actos, some patients and healthcare providers may consider alternative treatments for type 2 diabetes. What are some alternatives to Actos?

Other Oral Diabetes Medications

Several classes of oral medications can be used to manage type 2 diabetes, including:

• Metformin (Glucophage): Often considered the first-line treatment for type 2 diabetes
• Sulfonylureas: Stimulate the pancreas to produce more insulin
• DPP-4 inhibitors: Help the body continue to make insulin and reduce glucose production
• SGLT2 inhibitors: Help the kidneys remove excess sugar through urine
• GLP-1 receptor agonists: Slow digestion and help lower blood sugar levels

Injectable Medications

For some patients, injectable medications may be necessary. These include:

• Insulin: Various types and formulations are available
• GLP-1 receptor agonists: Some forms are available as injections

Lifestyle Interventions

In some cases, particularly in the early stages of type 2 diabetes, lifestyle changes alone may be sufficient to manage the condition. These interventions include:

• Dietary modifications
• Increased physical activity
• Weight loss (if overweight or obese)
• Stress management

The choice of treatment depends on various factors, including the severity of diabetes, overall health status, potential drug interactions, and individual preferences. It’s essential to work closely with a healthcare provider to determine the most appropriate treatment plan.

In conclusion, while Actos can be an effective medication for managing type 2 diabetes, it comes with significant risks and potential side effects. Patients and healthcare providers must carefully weigh the benefits against the risks when considering Actos as a treatment option. Regular monitoring, patient education, and a comprehensive approach to diabetes management are crucial for those using this medication. As with any medical treatment, open communication between patients and healthcare providers is key to ensuring the best possible outcomes.

Side Effects, Safety & FDA Warnings

Actos lowers blood sugar by increasing the body’s sensitivity to insulin and reducing the amount of glucose the liver releases. This allows the body to better remove excess blood sugar.

Its manufacturer, Takeda Pharmaceuticals America Inc., makes two additional versions of the drug that combine the active ingredient pioglitazone with metformin: Actoplus Met and Actoplus Met XR (extended release). Two other products combine pioglitazone with other diabetes drugs: glimepiride (Duetact) and alogliptin (Oseni).

The Food and Drug Administration (FDA) approved Actos in 1999, Actoplus Met in 2005, Actoplus Met XR in 2009. Duetact in 2006, and Oseni in 2013.

Eli Lilly partnered with Takeda to market Actos, and it became one of the most successful diabetes medications of all time. In 2007, it ranked as the world’s best-selling diabetes drug after studies linked rival drug Avandia to a higher risk of heart attack. Both come from the same family of drugs: thiazolidinediones or TZDs.

Before the medication’s patent expired in 2011, it had brought in $3.58 billion in United States sales in 2010. The drug’s sales made up 27 percent of Takeda’s revenue.

However, numerous studies and a review by the FDA linked higher dosages and prolonged use of the drug to an increased risk of bladder cancer.

In its 2015 annual report, Takeda said it had set aside $2.7 billion to cover the costs of settling Actos lawsuits that blamed the drug for bladder cancer and other injuries. Despite the lawsuits and FDA review, doctors can still prescribe the drug in the United States.

Meanwhile, health regulators in Germany and France ordered Takeda to pull the drug off the market in 2011 after an analysis of a company-sponsored study showed an increased risk of developing bladder cancer or heart problems. The government in India also banned the drug.

Important Information on Taking Actos

Actos is meant to be used along with diet and exercise to improve blood sugar control in adults with Type 2 diabetes. Depending on how well your body naturally controls blood sugar, your doctor may prescribe pioglitazone by itself or with other diabetes medications.

The medicine comes in a tablet, and you should take it only as directed by your doctor. Instructions in the drug’s label say take it once a day with or without food.

Typically, the dose starts at 15 mg or 30 mg, but some people may require a higher dose. Doctors can increase the dose by 15 mg at a time up to a maximum of 45 mg daily.

One 2022 study noted that for edema, weight gain and heart failure, the risk estimates for pioglitazone were lower for subjects taking less than 45 mg daily. The researchers concluded that lower doses of pioglitazone appear to confer similar benefits with fewer adverse effects than the recommended dose.

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15 mg, 30 mg and 45 mg Actos tablets.

Do not change your dose unless your doctor tells you to. Let your doctor know if you are in an accident, undergo surgery, or develop a fever or an infection. Experiences like these can put added stress on your body, and your doctor may need to alter your dose.

It’s important to continue to follow your diet and exercise regimen and routinely test your blood sugar. Your doctor will likely test your hemoglobin A1C to gauge whether the medication is working. Your doctor should also examine your eyes on a regular basis because the medicine can cause a build-up of fluid in the eyes and affect your vision.

Risks to Discuss with Your Doctor Before Starting Treatment

Before prescribing Actos, your doctor should order certain blood tests, including ones that check for liver problems. They may decide against prescribing the drug to patients with certain conditions, so it’s important to tell your doctor about your medical history.

Let your doctor know if you have heart failure, liver problems, Type 1 diabetes, or diabetic ketoacidosis in the past. Patients with Type 1 diabetes or who have had diabetic ketoacidosis in the past should not take Actos, nor should children younger than 18 years old. Patients with heart failure or liver problems should be watched carefully in case these conditions worsen while taking Actos.

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Source: Actos Medication Guide

Also tell your doctor if you have been diagnosed with bladder cancer or macular edema, which is a diabetic eye disease that causes swelling in the back of the eye.

Pioglitazone can increase the chances of becoming pregnant in some people and can harm your unborn baby. The medicine also passes into breast milk and can affect a nursing baby.

Talk to your doctor about birth control options and let them know if you are pregnant or plan to become pregnant, or are breastfeeding or plan to breastfeed.

Other medicines, vitamins or supplements you take can interact with pioglitazone and cause problems. For example, combining Actos with insulin or other antidiabetic medications can increase your risk of developing very low blood sugar, so a doctor may reduce the dose of the other diabetes drug.

Show your doctor or pharmacist a list of everything you take before you start using a new medication, so they can determine whether to adjust your dose or prescribe a different treatment.

Potential alternatives to Actos include Amaryl (glimepiride), Glucotrol (glipizide) and DiaBeta (glyburide). Prandin (repaglinide), Precose (acarbose) or Symlin (pramlintide) may also be substitutes for pioglitazone. As with Actos, these drugs can either be used alone or with another medication.

Common Side Effects

The most common side effects reported during Actos clinical trials were upper respiratory tract infection, headache, sinus infection, muscle pain and sore throat.

Other reported side effects included swelling, weight gain, back pain, dizziness, gas and diarrhea. The drug’s label says to call your doctor if you experience these side effects and they get worse or don’t go away.

Actoplus Met and Actoplus Met XR can cause the same side effects as Actos, but they can also cause side effects of metformin such as lactic acidosis, a life-threatening condition that occurs when too much lactic acid builds up in the body. Duetact can cause the same side effects as Actos, but it can also cause side effects of glimepiride such as very low blood sugar. Oseni can cause the same side effects as Actos, but it can also cause side effects of alogliptin, such as pancreas or kidney problems.

As of September 2019, the FDA Adverse Events Reporting System (FAERS) Public Dashboard showed 20,135 reports of complications possibly related to Actos since 1999. Of these, 16,404 were flagged as serious, including 2,725 deaths. The FDA points out that the medication may not have been the direct cause of the complications or deaths.

Congestive Heart Failure Black Box Warning

Actos has a black box warning for congestive heart failure. A black box warning is the most serious type of warning the FDA requires on a drug label.

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Source: Actos blackbox warning.

The boxed warning says Actos and other TZDs can cause fluid to buildup in the body when used alone or with other antidiabetic drugs, particularly insulin. This can lead to congestive heart failure or make the condition worse in some patients.

Doctors should carefully monitor patients for signs of heart failure such as rapid weight gain, trouble breathing, or swelling. This is especially the case after a patient first starts treatment or after dose increases.

Combining the drug with insulin may also increase the risk. And so can using the drug if you have New York Heart Association (NYHA) Class III or IV heart failure (more severe forms of heart failure).

Because of the risk, the drug is not recommended for patients with symptoms of heart failure or NYHA Class III or IV heart failure.

The FDA based this warning on clinical trials Takeda had conducted before it released the drug. In one study called the PROactive trial, 5,238 patients with Type 2 diabetes and preexisting heart disease were treated with Actos or a placebo. According to the results, more pioglitazone patients experienced a serious heart failure event than those who had taken the placebo.

In addition, congestive heart failure caused more people to drop out of the trial than any other serious adverse event. About 1.3 percent of pioglitazone patients withdrew from the trial because of the side effect compared to 0.6 percent of patients who had taken a placebo.

FDA Bladder Cancer Review

The FDA alerted the public about a possible risk of bladder cancer in September 2010 and in June 2011 based on results from the first five years of a 10-year study of whether Actos is associated with an increased risk of bladder cancer.

In December 2016, the agency updated the labels of all drugs that contain pioglitazone to warn that an increased risk of bladder cancer has been shown in some studies, but not all. While Takeda’s 10-year study ultimately did not find an increased risk, the PROactive clinical trial and a study using data from the United Kingdom did. The agency also noted early animal studies had shown bladder tumors in rats.

The updated drug labels recommended doctors not prescribe the drugs to patients with active bladder cancer and use caution when prescribing the drugs to patients with a prior history of bladder cancer.

“Overall, we conclude that pioglitazone may be associated with an increased risk in urinary bladder cancer, and we have updated the drug labels to include information about these additional studies.”

“Overall, we conclude that pioglitazone may be associated with an increased risk in urinary bladder cancer, and we have updated the drug labels to include information about these additional studies,” the FDA said.

According to the most recent data from the FDA, bladder cancer is the most frequently reported reaction to Actos. With more than 8,600 reports, it accounts for 46 percent of all adverse events reported to the FAERS database involving the drug.

Recent Bladder Cancer Studies

• 2019

  A review and meta-analysis published in Diabetology International found a “small but statistically significant” increase in the risk of bladder cancer in patients who had ever used pioglitazone compared to patients who had never used the drug. The authors concluded that alternative explanations for this increased risk could not be ruled out.

• 2018

  A review and meta-analysis published in Cancer Medicine found a “slightly but significantly increased risk of bladder cancer.” The authors also found increased risk was tied to higher doses and prolonged use.

• 2017

  A study published in Diabetes, Obesity and Metabolism analyzed Medicare data from nearly a quarter-million beneficiaries. Researchers found a “small absolute increase in risk of bladder cancer” among Actos users compared to people taking other diabetes drugs. They reported the increased risk appeared within the first two years of drug use and continued to increase the longer people took pioglitazone.

• 2016

  A population-based cohort study published in the British Medical Journal found pioglitazone was associated with an increased bladder cancer risk. The researchers looked at medical records of 145,000 people treated with different diabetes drugs in the same class. They found an increased risk and said it was specific to pioglitazone.

Fracture and Liver Failure Risks

The PROactive clinical trial also found an increase in the number of women who took pioglitazone and had bone fractures. Fractures were most likely to happen in the hands, forearms, feet, ankles, and legs, according to information in the drug’s label.

The trial followed participants for nearly three years, and researchers started noticing the difference in female patients after the first year. The trial did not see the same increased risk for men who took the drug.

BONE FRACTURES

5.1 percent of women who took Actos during the PROactive trial had bone fractures compared to 2.5 percent of women who took a placebo.

Source:

Actos Label

A more recent study published in The Journal of Clinical Endocrinology & Metabolism in 2017 also found an increased risk of fractures among people who had taken the drug. The clinical trial followed 3,876 stroke patients for roughly five years.

Researchers found 8.8 percent of those who had taken a placebo had fractures during that time. But those taking pioglitazone had increased relative risks ranging from 47 percent to 60 percent, depending on the type of fracture.

However, a combined analysis of several studies from 2018 did not find an association with pioglitazone and fracture risk.

After Actos became available in the United States, the FDA and Takeda received reports of some fatal and nonfatal cases of liver failure. The drug’s label says there is no way to definitively prove that pioglitazone does not cause liver issues.

It advises doctors to “use caution in patients with liver disease.” It also tells them to test each patient’s liver prior to prescribing the drug and to monitor each patient for signs of liver damage, including fatigue, loss of appetite, right upper abdominal discomfort, dark urine, or yellowed skin (jaundice).

What They Are and How to Manage Them

Actos (pioglitazone) is a prescription drug that’s used to help manage blood sugar levels in people with type 2 diabetes. Actos can cause side effects that range from mild to serious. Examples include heart failure and weight gain.

Actos is used along with diet and exercise to help manage blood sugar in adults with type 2 diabetes. It isn’t approved to treat type 1 diabetes.

The active ingredient in Actos is pioglitazone. (An active ingredient is what makes a drug work.) The drug comes as a tablet that you’ll swallow.

Keep reading to learn about the common, mild, and serious side effects (also called adverse effects) that Actos can cause. For a general overview of the drug, including details about its uses, see this article.

Some people may experience mild or serious side effects during their Actos treatment.

Examples of commonly reported side effects of Actos include:

• infections*
• headache
• sore throat
• muscle aches
• swelling, usually in your feet, ankles, or lower legs

* To learn more about this side effect, see the “Side effects explained” section below.

Keep reading to learn about other possible mild and serious side effects of Actos.

Some people may have mild side effects while taking Actos.

Examples of mild side effects that have been reported with Actos include:

• weight gain*
• infections*
• headache
• sore throat
• muscle aches
• flatulence (gas)
• back pain
• dizziness

* To learn more about this side effect, see the “Side effects explained” section below.

In most cases, these side effects should be temporary. And some may be easily managed, too. But if you have any symptoms that are ongoing or that bother you, talk with your doctor or pharmacist. And don’t stop using Actos unless your doctor recommends it.

Actos may cause mild side effects other than the ones listed above. See the Actos prescribing information for details.

Note: After the Food and Drug Administration (FDA) approves a drug, it tracks side effects of the medication. If you’d like to notify the FDA about a side effect you’ve had with Actos, visit MedWatch.

In rare cases, serious side effects can occur with Actos.

Serious side effects that have been reported with Actos include:

• swelling, usually in your feet, ankles, or lower legs
• bladder cancer
• low blood sugar level
• high blood pressure
• liver problems, such as liver failure
• macular edema (swelling in part of the eye)
• broken bones
• congestive heart failure*
• allergic reaction†

* Actos has a boxed warning for this side effect. This is the most serious warning from the Food and Drug Administration (FDA). To learn more, see the “Side effects explained” section below.
† An allergic reaction is possible after using Actos. But this side effect wasn’t reported in studies. To learn more about this side effect, see the “Side effects explained” section below.

If you develop serious side effects while taking Actos, call your doctor right away. If the side effects seem life threatening or if you think you’re having a medical emergency, immediately call 911 or your local emergency number.

Get answers to some frequently asked questions about the side effects of Actos.

Do side effects of Actos vary depending on whether I take the drug on its own or with metformin?

Yes, it’s possible for side effects to vary depending on whether you take Actos with metformin.

Your doctor may prescribe Actos along with other diabetes drugs to help manage your blood sugar level. In studies, Actos was prescribed in combination with metformin (Fortamet, Glumetza, Riomet), insulin, or sulfonylureas, such as glimepiride (Amaryl) and glipizide (Glucotrol XL).

When Actos is used with metformin,* most side effects of Actos are typically the same as when Actos is used by itself. But metformin commonly causes digestive problems, such as nausea, vomiting, constipation, and diarrhea. So you may experience these side effects if you take Actos with metformin.

For a list of side effects that may occur when Actos is taken with metformin, see the prescribing information for Actos. You can also talk with your doctor or pharmacist.

* Pioglitazone, the active drug in Actos, is available together with metformin as a generic drug and as the brand-name drug ActoPlus MET. For details on this drug combination, including possible side effects, see this article.

Does my risk of side effects from Actos depend on the strength I take (15 mg, 30 mg, or 45 mg)?

Yes. Certain side effects of Actos are dose-dependent, meaning your risk of these side effects is greater at higher doses.

In studies of Actos, weight gain* and swelling were more likely to occur at higher doses of the drug.

If you have other questions about what to expect with Actos based on the strength you’re prescribed, talk with your doctor or pharmacist.

* To learn more about this side effect, see the “Side effects explained” section below.

Will I need to have any lab tests to monitor for side effects of Actos?

Yes, it’s possible you may need lab tests to monitor for side effects of Actos.

In rare cases, taking Actos may lead to liver problems, such as liver failure. If you have liver problems before taking the drug, you may have a higher risk of this side effect.

Before you start treatment with Actos, your doctor will give you liver function tests. If your test results show you have liver disease, your doctor will let you know if it’s safe for you to take Actos.

If your doctor says it’s safe to take Actos, they’ll regularly check your liver function while you’re taking the drug. They may have you stop taking the drug if your liver function worsens over time.

To learn more about getting lab tests to monitor for side effects of Actos, talk with your doctor.

Learn more about some of the side effects Actos may cause.

Weight gain

Weight gain is a common side effect of Actos.

Weight gain can be caused by swelling, which is another possible side effect of Actos. Swelling from Actos usually happens in your feet, ankles, or lower legs.

Keep in mind that swelling and rapid weight gain can be symptoms of congestive heart failure (CHF). Rapid weight gain is defined as gaining more than 2 to 3 pounds in 24 hours or more than 5 pounds in 1 week. CHF is a possible serious side effect of Actos. To learn more, see “Congestive heart failure” right below.

What might help

If you’re concerned about weight gain with Actos, talk with your doctor. They can suggest ways to maintain a weight that’s healthy for you.

If you notice swelling or rapid weight gain while taking the drug, tell your doctor right away. They can check for other symptoms of heart failure and discuss a treatment plan.

Congestive heart failure

Actos has a boxed warning for the risk of new or worsening congestive heart failure (CHF). A boxed warning is the most serious warning from the Food and Drug Administration (FDA).

With CHF, your heart doesn’t pump blood to the rest of your body as effectively as it should.

In studies of Actos, CHF was a rare side effect. CHF can happen when you take the drug by itself or with other diabetes drugs. But your risk of CHF with Actos may be higher if you take the drug together with insulin.

Possible symptoms of CHF include:

• rapid weight gain (defined as gaining more than 2 to 3 pounds in 24 hours or more than 5 pounds in 1 week)
• swelling, especially in your feet, ankles, or lower legs
• shortness of breath
• increased heart rate
• confusion or trouble thinking

What might help

If you have symptoms of CHF, tell your doctor right away. It’s recommended that you avoid taking Actos if you have CHF with symptoms.

You shouldn’t take Actos if you have class 3 or class 4 heart failure. (These are types of serious heart failure.) Based on the type of heart failure you have, your doctor can tell you if Actos is right for you.

Infections

Infections are a common side effect of Actos. Infections that were reported in studies of Actos include sinus infections, upper respiratory infections, and urinary tract infections. The common cold is an example of an upper respiratory infection.

Symptoms will vary based on the specific infection you may have. But possible symptoms include:

• runny or stuffy nose
• headache
• fatigue (low energy)
• cloudy or bloody urine
• urinating more often than usual
• painful urination

What might help

If you have symptoms of an infection while taking Actos, talk with your doctor. They can suggest ways to manage your symptoms. They can also advise if treatments are available for the specific infection you have.

Allergic reaction

Like most drugs, Actos can cause an allergic reaction in some people. But this side effect wasn’t reported in studies.

Symptoms can be mild or serious and can include:

• skin rash
• itchiness
• flushing (temporary warmth, redness, or deepening of skin color)
• swelling under your skin, typically in your eyelids, lips, hands, or feet
• swelling of your mouth, tongue, or throat, which can make it hard to breathe

What might help

If you have mild symptoms of an allergic reaction, such as a mild rash, call your doctor right away. To manage your symptoms, they may suggest an over-the-counter antihistamine you take by mouth, such as Benadryl (diphenhydramine). Or they may recommend a product you apply to skin, such as hydrocortisone cream.

If your doctor confirms you had a mild allergic reaction to Actos, they’ll decide if you should continue using it.

If you have symptoms of a severe allergic reaction, such as swelling or trouble breathing, call 911 or your local emergency number right away. These symptoms could be life threatening and require immediate medical care.

If your doctor confirms you had a serious allergic reaction to Actos, they may have you switch to a different treatment.

Keeping track of side effects

During your Actos treatment, consider keeping notes on any side effects you’re having. Then, you can share this information with your doctor. This is especially helpful to do when you first start taking new drugs or using a combination of treatments.

Your side effect notes can include things such as:

• what dose of drug you were taking when you had the side effect
• how soon after starting that dose you had the side effect
• what your symptoms were from the side effect
• how it affected your daily activities
• what other medications you were also taking
• any other information you feel is important

Keeping notes and sharing them with your doctor will help your doctor learn more about how Actos affects you. And your doctor can use this information to adjust your treatment plan if needed.

In certain situations, it may not be safe to take Actos. Read on to learn more about possible warnings for Actos.

Boxed warning: Risk of congestive heart failure

Actos has a boxed warning for the risk of congestive heart failure (CHF). A boxed warning is the most serious warning from the Food and Drug Administration (FDA).

Taking Actos may lead to new or worsening CHF. It’s recommended that you avoid taking Actos if you have CHF with symptoms. You shouldn’t take Actos if you have class 3 or class 4 heart failure. (These are types of serious heart failure.)

To learn more, see the “Side effects explained” section above.

Other warnings

Actos may not be right for you if you have certain medical conditions or other factors that affect your health. Talk with your doctor about your health history before you take Actos. The list below includes factors to consider.

Bladder cancer. In rare cases, Actos may cause bladder cancer. If you currently have bladder cancer, be sure to tell your doctor before starting Actos treatment. They’ll likely prescribe a drug other than Actos for you.

Liver problems. Rarely, taking Actos may lead to liver problems, such as liver failure. If you have liver problems before taking the drug, you may have a higher risk of this side effect. Your doctor will monitor your liver function closely while you take Actos. Or they may prescribe a treatment other than Actos for your condition.

Osteoporosis. If you have osteoporosis, be sure to tell your doctor before you start taking Actos. Actos may cause broken bones, especially in the arms and legs. You may have a higher risk of this side effect if you have osteoporosis. Your doctor can advise if it’s safe for you to take Actos.

Allergic reaction. If you’ve had an allergic reaction to Actos or any of its ingredients, you shouldn’t take Actos. Ask your doctor what other medications are better options for you.

Irregular periods. Actos can cause ovulation, which raises the likelihood of pregnancy. This effect can occur in females* who don’t usually have ovulation as part of their menstrual cycle. Before you start taking Actos, be sure to tell your doctor if you have irregular periods. They may recommend that you use effective birth control while taking the drug.

* In this article, we use the term “female” to refer to someone’s sex assigned at birth. For information about the difference between sex and gender, see this article.

Alcohol and Actos

There aren’t known safety issues with drinking alcohol while taking Actos.

But keep in mind that alcohol can affect your blood sugar levels. Actos is used to help manage blood sugar levels in people who have type 2 diabetes. So you may need to limit the amount of alcohol you drink while taking the drug.

If you drink alcohol, talk with your doctor about the amount that’s safe for you to consume while taking Actos.

Pregnancy and breastfeeding while taking Actos

It isn’t known if Actos is safe to take during pregnancy or while breastfeeding.

If you’re pregnant or breastfeeding, or planning to become pregnant or breastfeed, talk with your doctor before starting Actos treatment.

Actos is used to treat type 2 diabetes. You may have mild side effects while taking the drug. In rare cases, you may experience serious side effects, such as bladder cancer.

If you have questions about side effects from Actos, talk with your doctor or pharmacist. Below are a few questions you may want to ask:

• How can I maintain a weight that’s healthy for me while taking Actos?
• Do I have a higher risk of any side effects of Actos?
• Will other drugs I’m taking raise my risk of side effects from Actos?

To learn more about Actos, see these articles:

• All About Actos
• Dosage for Actos: What You Need to Know

To get information on different conditions and tips for improving your health, subscribe to any of Healthline’s newsletters. You may also want to check out the online communities at Bezzy. It’s a place where people with certain conditions can find support and connect with others.

Q:

Is there anything I can do to lower my risk of broken bones as a side effect of Actos?

Anonymous

A:

Before you start taking Actos, you should talk with your doctor about your risk of bone fractures. Your doctor will likely perform tests such as a bone mineral density scan to check your bone health. This will help them create a plan for you so that you can take Actos with less risk of fractures.

If you have questions or concerns about bone fractures while taking Actos, talk with your doctor or pharmacist.

The Healthline Pharmacist TeamAnswers represent the opinions of our medical experts. All content is strictly informational and should not be considered medical advice.

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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 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.

what you need to know – Drink-Drink

Introduction

If you have type 2 diabetes, your doctor may suggest Actos (pioglitazone) as a treatment option. Along with other questions you may have about a drug, you may be interested in its side effects.

Actos is a prescription drug used to treat type 2 diabetes in adults*. It is used along with diet and exercise to control blood sugar levels.

Actos is available as tablets to be swallowed. Usually used as a long term treatment. For more information about Actos, see this detailed drug article.

Like all medicines, Actos can cause mild or serious side effects (also called side effects). Keep reading to find out more.

What are the most common side effects of Actos?

Some people may experience mild or severe side effects during treatment with Actos.

Examples of commonly reported side effects of Actos include:

• infections*
• Headache
• sore throat
• muscle pain
• swelling, usually in the legs, ankles, or lower legs 9 0020

Continue reading for other possible minor and serious side effects of Actos.

What are the mild side effects of Actos?

Some people may have mild side effects when taking Actos.

Examples of mild side effects reported with Actos include:

• weight gain*
• infections*
• Headache
• sore throat
• muscle pain
• flatulence (gas)
• back pain

9 0019 dizziness

In most cases, these side effects should be temporary. And some are easy to deal with. But if you have any symptoms that continue or bother you, talk to your doctor or pharmacist. And don’t stop using Actos unless your doctor recommends it.

Actos may cause mild side effects other than those listed above. See Actos prescribing information for details.

After the Food and Drug Administration (FDA) approves a drug, it monitors the drug’s side effects. If you would like to notify the FDA of a side effect you experienced while taking Actos, visit MedWatch.

What are the serious side effects of Actos?

In rare cases, when taking Actos, serious side effects may occur.

Serious side effects reported with Actos include:

• swelling, usually in the legs, ankles, or lower legs
• Bladder cancer
• low blood sugar
• high blood pressure
• liver problems such as liver failure
• macular edema (swelling in part of the eye)
• bone fractures
• chronic heart failure*
• allergic reaction†

If you develop serious side effects while taking Actos, call your doctor right away. If the side effects seem life-threatening or if you think you need a medical emergency, call 911 or your local emergency number right away.

Frequently Asked Questions About Actos Side Effects

Get answers to some frequently asked questions about Actos side effects.

Do the side effects of Actos change depending on whether I take the drug alone or with metformin?

Yes, side effects may vary depending on whether you are taking Actos with metformin.

Your doctor may prescribe Actos along with other diabetes medicines to help control your blood sugar. In studies, Aktos has been administered in combination with metformin (Fortamet, Glyumetsa, Riomet), insulin, or sulfonylurea derivatives such as glimepiride (Amaryl) and glipizide (Glucotrol).

When Actos is used with metformin*, most of the side effects of Actos are usually the same as when Actos is used alone. But metformin usually causes digestive problems such as nausea, vomiting, constipation, and diarrhea. Thus, you may experience these side effects if you are taking Actos with metformin.

For a list of side effects that may occur when taking Actos with metformin, see Actos prescribing information. You can also talk to your doctor or pharmacist.

Does my risk of side effects from Actos depend on the dose I take (15mg, 30mg or 45mg)?

Yes. Some side effects of Actos are dose-dependent, meaning that the risk of these side effects is higher at higher doses.

In the Actos studies, weight gain* and edema were more frequently observed at higher doses of the drug.

If you have any other questions about what to expect from Actos depending on the concentration you are prescribed, talk to your doctor or pharmacist.

Will I need any lab tests to monitor the side effects of Actos?

Yes, you may need laboratory tests to monitor the side effects of Actos.

In rare cases, taking Actos can lead to liver problems, such as liver failure. If you had liver problems before taking the drug, you may be at a higher risk of this side effect.

Your doctor will order liver function tests before you start treatment with Actos. If the test results show that you have liver disease, your doctor will tell you if it is safe for you to take Actos.

If your doctor says it is safe to take Actos, they will check your liver function regularly while you are taking the drug. They may ask you to stop taking the drug if your liver function deteriorates over time.

Talk to your doctor to learn more about doing laboratory tests to monitor the side effects of Actos.

Side effects explained

Find out more about some of the side effects Actos may cause.

Weight gain

Weight gain is a common side effect of Actos.

Weight gain may be due to edema, which is another possible side effect of Actos. Swelling from Actos usually occurs in the feet, ankles, or lower legs.

Be aware that swelling and rapid weight gain may be symptoms of congestive heart failure (CHF). Rapid weight gain is defined as gaining more than 2-3 pounds in 24 hours or more than 5 pounds in 1 week. CHF is a possible serious side effect of Actos. To learn more, see the Congestive Heart Failure section below.

What can help

If you are concerned about weight gain while taking Actos, talk to your doctor. They can suggest ways to maintain a healthy weight.

If you notice swelling or rapid weight gain while taking this medicine, tell your doctor right away. They can check for other symptoms of heart failure and discuss a treatment plan.

Chronic heart failure

Actions must be a warning in the box for new or worsening congestive heart failure (CHF). The boxed warning is the most serious warning from the Food and Drug Administration (FDA).

With CHF, your heart is not pumping blood to the rest of the body as efficiently as it should.

CHF was a rare side effect in the Actos studies. CHF can happen when you take the drug alone or with other diabetes medicines. But your risk of CHF while taking Actos may be higher if you take the drug along with insulin.

Possible symptoms of CHF include:

• rapid weight gain (defined as gaining more than 2-3 pounds in 24 hours or more than 5 pounds in 1 week)
• swelling, especially in the legs, ankles, or lower legs
• shortness of breath
• increased heart rate
• confusion or trouble thinking

What can help

If you have symptoms CHF, tell your doctor immediately. It is recommended to avoid taking Actos if you have symptomatic CHF.

You should not take Actos if you have class 3 or 4 heart failure. (These are types of serious heart failure.) Depending on the type of heart failure, your doctor can determine if Actos is right for you.

Infections

Infections are a common side effect of Actos. Infections reported in the Actos studies include sinus infections, upper respiratory tract infections, and urinary tract infections. The common cold is an example of an upper respiratory tract infection.

Symptoms will vary depending on the specific infection you may have. But possible symptoms include:

• runny or stuffy nose
• Headache
• fatigue (low energy)
• cloudy or bloody urine
• urinating more often than usual
• painful urination

What can help

If you have symptoms of an infection while taking Aktos, talk to your doctor. They may suggest ways to manage your symptoms. They can also advise if treatments are available for the specific infection you have.

Allergic reaction

Like most medicines, Actos may cause an allergic reaction in some people. But this side effect was not reported in studies.

Symptoms may be mild or severe and may include:

• skin rash
• itching
• redness (temporary warmth, redness, or increased skin color)
• swelling under the skin, usually on the eyelids, lips, hands or feet

9 0019 swelling of the mouth, tongue, or throat that makes breathing difficult

What can help

If you have mild symptoms of an allergic reaction, such as a mild rash, call your doctor right away. To manage your symptoms, they may suggest an over-the-counter antihistamine you take by mouth, such as Benadryl (diphenhydramine). Or they may recommend a product you apply to your skin, such as a hydrocortisone cream.

If your doctor confirms that you had a mild allergic reaction to Actos, they will decide whether you should continue using it.

If you have symptoms of a severe allergic reaction, such as swelling or difficulty breathing, call 911 or your local emergency number right away. These symptoms can be life threatening and require immediate medical attention.

If your doctor confirms that you have had a serious allergic reaction to Actos, he may ask you to switch to another treatment.

Tracking side effects

Consider keeping a record of any side effects you experience during your treatment with Actos. You can then share this information with your doctor. This is especially helpful when you first start taking new medications or using a combination of treatments.

Your side effect notes may include things like:

• what dose of the drug you were taking when you had the side effect
• How soon after starting this dose did you experience a side effect
• What were your symptoms due to the side effect
• How did it affect your daily activities
• What other medications did you also take
• Any other information you think is important

Taking notes and sharing them with your doctor will help him learn more about how Actos affects you. And your doctor can use this information to adjust your treatment plan if necessary.

Warnings for Actos

It may not be safe to take Actos in certain situations. Read on to find out more about possible warnings for Actos.

Boxed warning: congestive heart failure

Actions must be boxed warning for congestive heart failure (CHF). The boxed warning is the most serious warning from the Food and Drug Administration (FDA).

Actos may cause or worsen CHF. It is recommended to avoid taking Actos if you have symptomatic CHF. You should not take Actos if you have class 3 or 4 heart failure. (These are types of serious heart failure.)

To learn more, see the “Explanation of side effects” section above.

Other warnings

Actos may not be right for you if you have certain medical conditions or other factors affecting your health. Talk to your doctor about your medical history before taking Actos. The list below includes factors to consider.

Bladder cancer. In rare cases, Actos may cause bladder cancer. If you currently have bladder cancer, be sure to tell your doctor before starting treatment with Actos. Most likely, you will be prescribed another drug, not Aktos.

Liver problems. In rare cases, taking Actos can lead to liver problems, such as liver failure. If you had liver problems before taking the drug, you may be at a higher risk of this side effect. Your doctor will monitor your liver function closely while you are taking Actos. Or they may prescribe a treatment other than Actos for your condition.

Osteoporosis. If you have osteoporosis, be sure to tell your doctor before you start taking Actos. Actos can cause broken bones, especially the arms and legs. You may be at a higher risk of this side effect if you have osteoporosis. Your doctor can advise if it is safe for you to take Actos.

Allergic reaction. If you have had an allergic reaction to Actos or any of its ingredients, you should not take Actos. Ask your doctor which other medicines are best for you.

Irregular periods. Actos may induce ovulation, which increases the risk of pregnancy. This effect may be seen in women* who do not normally ovulate during their menstrual cycle. Before you start taking Actos, be sure to tell your doctor if you have irregular periods. They may recommend that you use effective birth control while taking the drug.

Alcohol use and Actos

There are no known safety issues with drinking while taking Actos.

But be aware that alcohol can affect blood sugar levels. Actos is used to control blood sugar levels in people with type 2 diabetes. Therefore, you may need to limit the amount of alcohol you drink while taking the drug.

If you drink alcohol, talk to your doctor about the amount that is safe for you to take Actos.

Pregnancy and breast-feeding while taking Aktos

It is not known whether it is safe to take Actos during pregnancy or breast-feeding.

If you are pregnant or breastfeeding, planning to become pregnant or breastfeeding, talk to your doctor before starting treatment with Actos.

What to ask your doctor

Actos is used to treat type 2 diabetes. You may experience mild side effects while taking the drug. In rare cases, you may experience serious side effects such as bladder cancer.

If you have any questions about the side effects of Actos, talk to your doctor or pharmacist. Below are a few questions you can ask:

• How can I maintain a healthy weight while taking Actos?
• Am I at higher risk of any side effects of Actos?
• Will other medicines I take increase the risk of side effects from Actos?

For information and tips to help you manage your condition, subscribe to the Drink-Drink Type 2 Diabetes Newsletter.

Ask a pharmacist

Q:

Is there anything I can do to reduce my risk of broken bones as a side effect of Actos?

Anonymous

A:

Before you start taking Actos, you should talk to your doctor about the risk of bone fractures. Your doctor will likely run tests, such as a bone mineral density scan, to check the health of your bones. This will help them develop a plan for you so that you can take Actos with less risk of fractures.

If you have questions or concerns about broken bones while taking Actos, talk to your doctor or pharmacist.

Dena Westfalen, PharmD The answers represent the opinions of our medical experts. All content is for informational purposes only and should not be considered medical advice.

Registration data: Drink-Drink has made every effort to ensure that all information is accurate, complete and up to date. However, this article should not be used as a substitute for the knowledge and experience of a licensed healthcare professional. You should always check with 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 side effects. The absence of warnings or other information for a given medicinal product does not mean that the drug or combination of drugs is safe, effective, or suitable for all patients or for all specific uses.

“Diabetes is treated when the patient feels healthy” – Vademecum magazine

Drugs for the treatment of type 2 diabetes, a disease that is difficult to diagnose and expensive to treat, have been under the special control of the US Food and Drug Administration (FDA) for the past 10 years. The reason for the vigilant attention of the regulator is the high-profile scandal that erupted in 2007, caused by the publication of data on the risk of cardiovascular complications when using the glucose-lowering drug Avandia (rosiglitazone) from GSK. A year later, the FDA tightened the requirements for new antidiabetic drugs by placing a special barrier at the entrance to the market – clinical studies (CTs) confirming the absence of such side effects. Since then, players in the segment, estimated at $237 billion in 2017, have collectively spent about $2 billion on additional clinical trials.

Pharmaceutical manufacturers, of course, did not lose money by plunging these costs into the final cost of drugs. And when the FDA confirmed its determination in the fall of 2018 in the fight against the side effects of antidiabetic drugs, American patient organizations and doctors opposed the increase in the cost of therapy due to additional clinical trials.

Professor Itamar Ratz, Head of the Specialized Center at Hadassah University Hospital, who participated in international clinical trials of Forxiga (dapagliflozin) from AstraZeneca, spoke to Vademecum about how it is possible and necessary to resolve the conflict between the effectiveness, safety and excessive cost of drugs for the treatment of type 2 diabetes.

– Type 2 diabetes is one of the most common chronic diseases in the world, and there is little progress in its control even in developed countries. Why is that?

– The key problem is the failure of early diagnosis and start of treatment. Unfortunately, general practitioners (GPs) do not have enough knowledge to detect the disease at the very beginning. There are about 450 million people with diabetes in the world, and there are not enough specialists able to provide adequate therapy. In addition, one erroneous idea dominated for a long time – it is necessary to treat step by step, starting with the patient’s lifestyle, then prescribe hypoglycemic drugs. But it is difficult for people to change, most, of course, could not cope with this. Yes, and the drugs were prescribed not very effective, for example, those that work on the basis of metformin.

Over time, it became clear: if you want to cure diabetes, you need to start from the earliest stage and approach the solution of the problem in a comprehensive manner. The technique was proposed many years ago by Ralph DeFronzo [Professor, Head of the Diabetes Department at the Texas Health Science Center. – Vademecum] – treatment with a combination of drugs immediately after diagnosis.

But DeFronzo’s idea did not take root – it was hacked to death by the side effect of drugs, which, moreover, were not cheap. And the main issue today is treatment at an early stage, preventing the development of hyperglycemia. And here we again return to the shortage of specialists and the competence of GPs.

– How should the same GP conduct diagnostics in order to detect the disease at an early stage?

– Monitor blood glucose levels in patients at risk: those whose relatives had diabetes or whose parents had metabolic syndrome, hypertension, obesity, high blood lipids. Patients leading a “sedentary” lifestyle, and those are the majority, should also be the object of special attention. The best, but not from an organizational point of view, diagnostic method is a glucose tolerance test, when the patient is given 75 g of sugar, and then blood sugar levels are measured after an hour, two, three. Of course, the doctor does not have time for this. Imagine if every potential diabetic in Russia had such a test? Will not work.

Therefore, I see the most acceptable option as a plasma glucose test. If the score is above 100, the patient is already in a pre-diabetic state. Add to this the glycated hemoglobin (HbA1c) test, which will show the average blood sugar over a period of up to three months. If the indicator is in the range of 5–6.4, then this is a pre-diabetic condition. If more than 6.4 – this is already diabetes. It is important to refer the patient to these tests in time – not only to detect diabetes as such, but to prevent complications: such patients have a high risk of developing cardiovascular diseases and kidney failure. Even at the stage of prediabetes.

– In Russia, according to experts, at least 20 million people are in this state.

There are difficulties all over the world. First, patients with type 2 diabetes are poorly monitored. What is a good observation? This is a stabilization of the glycated hemoglobin at a level below 7. You will not find this even in half of the patients. Secondly, such patients are poorly treated – they do not try to prevent the degradation of kidney function and heart failure. If they are already there, then no matter how you lower your glucose level, this will not help. This will give some advantages, but will not fill the gap. Just think about it: the number of cardiovascular diseases in people with type 2 diabetes is on average twice as high as in other categories of patients, the number of cases of heart failure is 4-5 times more.

– What is the likelihood of complications?

– The risk of developing heart failure during the course of the disease, that is, already during therapy, reaches 15%, as well as renal failure. With other diseases, such as retinopathy, for example, we have been able to achieve excellent results, reducing the risk from 5-6% to 1-2%. As for the diabetic foot, in most countries amputation is already rare – up to 5% of the total number of diabetics. By the way, the ulcer is more common – up to 10%. The figures for the ulcer are also falling, but not as fast as we would like.

The problem is also that it is customary to treat a patient when he already has clinical symptoms. But if the estimated glomerular filtration rate of the kidneys drops to 50 or 40, then this means that the kidneys are only 40% functioning, that is, it is already too late to treat a person. The situation is similar with the heart. If the patient has suffered to heart failure, then nothing can be repaired. It is necessary to treat when the patient feels healthy.

– What prevents this if the diagnosis has already been made?

– I’ll use the example of Israel. The system is well organized, but we are making one huge mistake. The results of the examination of kidney function, which the doctor relies on, allow a serious error in such an indicator as creatinine clearance. It is usually indicated that it is above or below 60. That is, if you have 65, 75, then you, it turns out, are healthy. Although a healthy person has an indicator of 120, and 90 is already the beginning of kidney failure. What we have? The doctor sees an indicator “above 60” and believes that the patient has no problems, nothing further needs to be looked at. The situation with heart failure is even more difficult. The patient does not complain about anything, and the examination of the ejection fraction of the heart in many does not say anything. You can’t send all diabetics for an ECG – it’s costly and pointless.

The only working option, it seems to me, may be drug therapy, of course, if the drug is not too expensive and has an associated hypoglycemic effect on the cardiovascular system and kidneys. There are such drugs on the market, and in any case, 30-40% of patients will be able to prevent kidney or heart failure. I cannot say, however, that this approach is popular even in Israel. And in Europe, and indeed around the world, at least 40% of patients are still receiving drugs of the sulfonylurea class – these are bad, unsafe drugs. They can cause hypoglycemia, weight gain, and may even increase the risk of cardiovascular disease.

– Why use them then?

– I have no explanation for this. Maybe the American and European Diabetes Associations need time to study the drugs, to be told, “Here are some good drugs, they’ve been on the market for 10 years.” I think it’s a matter of time. Israel has 600,000 type 2 diabetics per 8 million population. This is one in ten Israelis over the age of 20. Only a general practitioner can treat it.

The only thing we can do is to give such a doctor medicine and the opportunity to start treatment as soon as possible. Do you know what is the average life expectancy of a patient with type 2 diabetes on dialysis? Somewhere 2.5 years. If a kidney transplant is performed, then we will extend the life of a person up to 10 years, but this is an extreme method.

At the same time, there are hypoglycemic drugs that I am talking about, which are included in the class of SGLT-2 inhibitors. Our Declare study showed that these drugs are safe, help reduce patient weight, normalize blood pressure, reduce micro- and macroalbuminuria of the kidneys, fight hyperglycemia, and, we believe, have a positive effect on heart function. All this is important, since 90% of diabetics have high blood pressure and/or obesity.

– The Declare study you participated in, I understand, has more to do with FDA requirements than with looking for conjugate effects. What do you think about the scandal with Avandia, which, in fact, provoked the tightening of regulatory control over hypoglycemic drugs?

– I was not initially among those who attacked GSK with accusations. In my opinion, the meta-analysis of the results of the Avandia study, presented in 2008, was badly written. By the way, the FDA then even made a proposal not to remove the drug from the market. It did not help. I know that Actos from Takeda is now mainly used. It reduces the number of cardiovascular complications by 15% – this is a great result. However, Actos is contraindicated in menopause, can cause brittle bones, fluid retention in the body, weight gain, and all this is bad.

– Are there any drugs in the SGLT-2 inhibitor class already on the market?

– Yes, for example, canagliflozin has been on the US market for many years. Or a new drug based on ertugliflozin [FDA-approved in late 2017 Steglatro by MSD. – Vademecum]. Other drugs of this group are on the way, they will all have similar properties. However, canagliflozin has been criticized for the risk of diabetic foot development and consequent amputation. But, say, empagliflozin [by Boehringer Ingelheim. – Vademecum] and AstraZeneca dapagliflozin are near-perfect drugs that are indicated for most, if not all, type 2 diabetic patients.

– How intense will competition be between Boehringer Ingelheim and AstraZeneca for drugs in this class?

“Business is competitive, it’s true, but we doctors don’t care. In fact, the Declare study expands the use of dapagliflozin in patients even without cardiovascular disease. However, these studies cannot be directly compared with each other because they included different groups of patients.

– Has the FDA recognized the results of this study?

“I don’t need FDA approval to see results. What results am I talking about? In addition to those mentioned above, we are talking about the effect of the drug on the kidneys. We took patients with creatinine clearance above 60, that is, seemingly “healthy”. We used to give metformin to such patients, then we realized that after it, if it didn’t help, we still had to wait two or three years before prescribing something else. And as you know, the doctor does not have time. But if you give the patient metformin in combination with an SGLT-2 inhibitor, then the glucose level, weight, pressure will decrease, and, importantly, we will get a preventive effect on kidney failure.