Pioglitazone, sold under the brand name Actos among others, is an anti-diabetic medication used to treat type 2 diabetes. It may be used with metformin, a sulfonylurea, or insulin. Use is recommended together with exercise and diet. It is not recommended in type 1 diabetes. It is taken by mouth.
Common side effects include headaches, muscle pains, inflammation of the throat, and swelling. Serious side effects may include bladder cancer, low blood sugar, heart failure, and osteoporosis. Use is not recommended in pregnancy or breastfeeding. It is in the thiazolidinedione (TZD) class and works by improving sensitivity of tissues to insulin.
Pioglitazone was patented in 1985, and came into medical use in 1999. It is available as a generic medication. In 2020, it was the 168th most commonly prescribed medication in the United States, with more than 3million prescriptions. It was withdrawn in France and Germany in 2011.
Medical uses
Pioglitazone is used to lower blood glucose levels in type 2 diabetes either alone or in combination with a sulfonylurea, metformin, or insulin. The effects of pioglitazone have been compared in a Cochrane systematic review to that of other blood sugar lowering-medicine, including metformin, acarbose, and repaglinide, as well as with appropriate diet and exercise, not showing any benefit in reducing the chance of developing type 2 diabetes in people at risk. It did, however, show reduction of risk of developing type 2 diabetes when compared to a placebo or to no treatment. These results should be interpreted considering that most of the data of the studies included in this review were of low or very-low certainty.
While pioglitazone does decrease blood sugar levels, the main study that looked at the medication found no difference in the main cardiovascular outcomes that were looked at. The secondary outcome of death from all causes, myocardial infarction, and stroke were lower.
Pioglitazone has been found to reduce all-cause mortality in type 2 diabetic patients compared to other therapies, with a 60% reduction in mortality in those exposed to pioglitazone, compared to those never exposed. Another study found an all-cause mortality hazard ratio of 0.33 for pioglitazone after adjusting for >40 covariates, compared to insulin. Due to insufficient data on all-cause mortality, cardiovascular mortality, myocardial infarction and stroke, this was not possible to compare in a more recent review.
Contraindications
Pioglitazone cannot be used in patients with a known hypersensitivity to pioglitazone, other thiazolidinediones or any of components of its pharmaceutical forms. It is ineffective and possibly harmful in diabetes mellitus type 1 and diabetic ketoacidosis. Its safety in pregnancy, lactation (breastfeeding) and people under 18 is not established.
Given previous experiences with the related drug troglitazone, acute diseases of the liver are regarded as a contraindication for pioglitazone.
Side effects
A press release by GlaxoSmithKline in February 2007 noted that there is a greater incidence of fractures of the upper arms, hands and feet in female diabetics given rosiglitazone compared with those given metformin or glyburide. The information was based on data from the ADOPT trial. Following release of this statement, Takeda Pharmaceutical Company, the developer of pioglitazone (sold as Actos in many markets) admitted that it has similar implications for female patients.
The risk of hypoglycemia is low in the absence of other drugs that lower blood glucose.
Pioglitazone can cause fluid retention and peripheral edema. As a result, it may precipitate congestive heart failure (which worsens with fluid overload in those at risk). It may cause anemia. Mild weight gain is common due to increase in subcutaneous adipose tissue. In studies, patients on pioglitazone had an increased proportion of upper respiratory tract infection, sinusitis, headache, myalgia and tooth problems.
Chronic administration of the drug has led to occasional instances of cholestatic hepatitis, reversible upon drug discontinuation.
On July 30, 2007, an Advisory Committee of the Food and Drug Administration concluded that the use of rosiglitazone for the treatment of type 2 diabetes was associated with a greater risk of "myocardial ischemic events" when compared to placebo, but when compared to other diabetes drugs, there was no increased risk. Pioglitazone is currently being reviewed. A meta-analysis released subsequently showed that pioglitazone reduced the risk of ischemic cardiac events rather than increased the risk, but increased CHF.