Side effects of pioglitazone, the efficacy of pioglitazone (Actos)

In this article, we will talk about pioglitazone efficacy for diabetes, side effects. Does it cause bladder cancer? Is wight again associated with pioglitazone (Actos) a big problem? How about bone fractures associated with it? Will it cause or prevent heart attacks or heart failure? How to remedy or prevent side effects. Who is a good candidate?

How does pioglitazone work?

The thiazolidinediones (pioglitazone, rosiglitazone) increase insulin sensitivity by acting on fat tissue and muscle tissue to increase glucose uptake. Also, they decrease glucose production by the liver which is a minor effect.

Which patient is a good candidate for pioglitazone (Actos)?

Generally, pioglitazone and rosiglitazone are not prescribed as initial therapy in patients with type 2 diabetes. It is definitely not indicated for patients with type 1 diabetes
Pioglitazone may still offer an advantage in severe insulin resistance, coexisting nonalcoholic fatty liver disease (NASH), or history of a recent stroke.

What are the common problems associated with pioglitazone (Actos)?

Risks of weight gain, fractures, heart failure, and potential concerns about a possible small increase in the risk of bladder cancer require careful risk-benefit discussion with the patient.
Lower doses should be used when possible to minimize potential adverse effects, especially when it comes to weight gain and edema. As a general principle, we individualized the choice and doses of type 2 diabetes mellitus medications.

On the other hand, nowadays we use rosiglitazone rarely because of the concern about a potential increased risk for cardiovascular events suggested by a controversial meta-analysis of phase III clinical trials.

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Which patients should not use pioglitazone (Actos)

1. Patients who have heart failure or any evidence of fluid overload
2. Diabetic patient with a history of fracture or at high risk for fracture(more common in women)
3. Patients with diabetes who have active liver disease (liver enzyme>2.5 times above the upper reference limit)
4. Anybody active or history of bladder cancer
5. Type 1 diabetic patient
6. Diabetes during pregnancy

We typically start at 50 mg daily if, after a few weeks, there is inadequate control based upon fasting blood glucose values, we increase the daily dose by 15 mg up to the maximum dose of 45 mg daily. However, the side effects of weight gain and edema likely to happen at higher doses.

How effective is it in treating diabetes? Does pioglitazone (Actos) reduce A1c levels?

When thiazolidinediones are used as monotherapy, the expected decrease in A1C is approximately 0.5 to 1.4 percent. In some cases that can be even more than 2% if starting A1c is more than 10%.

Does pioglitazone increase the risk of heart failure or heart attacks?

Both pioglitazone and rosiglitazone increase the risk of heart failure, especially when used with insulin.
In 2010, the US Food and Drug Administration (FDA) imposed restrictions on the prescribing of rosiglitazone because of concerns about the increased risk of heart attacks. These restrictions were largely removed by the FDA in 2013 after a reevaluation of the Rosiglitazone Evaluated for Cardiac Outcomes and Regulation of Glycaemia in Diabetes (RECORD) study. However, pioglitazone does not have any indication that it would increase heart attacks. There are some significant indications that it can reduce the risk of heart attacks.

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Can patients with fatty liver benefit from pioglitazone (Actos)

Yes, in patients with type 2 diabetes mellitus and biopsy-proven nonalcoholic fatty liver disease (NASH) pioglitazone can improve inflammation in the liver. The fatty liver typically is a result of excessive abdominal weight gain.

Does pioglitazone (Actos) cause low blood sugar (hypoglycemia)?
Pioglitazone improves blood glucose primarily by increasing insulin sensitivity. Therefore, it is much less likely to cause low blood sugar (hypoglycemia) than sulfonylureas (glipizide, glyburide, glimepiride) or insulins.

Can pioglitazone (Actos) increase the risk of bone fractures?

There is significant evidence that pioglitazone can reduce bone density and increase fracture risk, particularly in women. The wrist does not appear to be as high in men.
Although, the real risk increase in fractures risk appears to be small. Nevertheless, we do not use it in women with low bone density or other risk factors for fracture.

Does pioglitazone (Actos) increase the risk of bladder cancer?

There are some concerns about the association between bladder cancer and pioglitazone (Actos) although at best this association is controversial, and studies have yielded conflicting results. As a reasonable precaution, we do not use pioglitazone in patients with active bladder cancer.
A 10-year observational study of pioglitazone use in patients with diabetes, there was not a significant association between pioglitazone exposure and bladder cancer among patients with an average use of 2 years.

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Can pioglitazone cause eye problems or macular edema?

Although we do not know how frequent it is there are some reports linking pioglitazone and macular edema. On the other hand, in the randomized clinical trial Action to Control Cardiovascular Risk in Diabetes (ACCORD) data from 3473 participants did not demonstrate a conclusive link.

Most common adverse Reactions from pioglitazone (Actos)

You can expect the following adverse reactions from pioglitazone (Actos):
Swelling, mostly around the ankles
Low blood sugar if combined with a sulfonylurea or insulin. Increase the frequency of blood sugar checks every time you start any antidiabetic medication.
Increased risk of catching a cold, upper respiratory infection etc.Increases risk of heart failure if taken together with insulin.
Headaches may increase. The reason for increased headaches is unknown.
Potential increased risk of bone fractures especially in postmenopausal women
Potential weight gain if used by itself or combined with insulin or sulfonylurea.

Can breastfeeding women take pioglitazone (Actos)?

Based on the current studies we do not know whether pioglitazone is present in breast milk.
According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and the benefits of treatment to the mother.
In our practice, we do not use pioglitazone frequently on breast-feeding women.

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Can I use it with other antidiabetic medications?

Definitely. Although you will need to continue to monitor your blood sugars. If there is an interaction with another medication you will need to monitor both treatments carefully.

To summarize, although pioglitazone is not the first therapy to be used to treat diabetes it still has overall in patients with significant insulin resistance and nonalcoholic fatty liver disease. We use pioglitazone very carefully on female patients who are postmenopausal due to the potential increased risk of bone fractures. We do not use this medicine on patients who have a history or active bladder cancer due to questionable increased risk. Patients who take pioglitazone (Actos) should be very careful about the increased risk of fluid retention, edema, and increased risk of heart failure especially when at this combined with insulin.

Ahmet Ergin, MD, FACE, CDCES, ECNU
Endocrinology
2260 Palm Beach Lakes Blvd. Ste 212 Unit #7
West Palm Beach, Florida