Pioglitazone detailed information
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Pioglitazone is a prescription drug of the class thiazolidinedione with hypoglycemic (antihyperglycemic, antidiabetic) action.
Pioglitazone is marketed as trademarks Actos in the USA and Glustin in Europe by the pharmaceutical company Takeda.

# Pharmacology
Pioglitazone selectively stimulates nuclear receptor peroxisone proliferator-activated receptor gamma (PPAR). It modulates the transcription of the insulin-sensitive genes involved in the control of glucose and lipid metabolism in the lipidic, muscular tissues and in the liver. As a result, pioglitazone reduces insulin resistance in the liver and peripheral tissues; increases the expense of insulin-dependent glucose; decreases withdrawal of glucose from the liver; reduces quantity of glucose, insulin and glycated haemoglobin in the bloodstream. Although not clinically significant, pioglitazone decreases the level of triglycerides and increases that of high-density lipoproteins (HDL) without changing low-density lipoproteins (LDL) and total cholesterol in patients with disorders of the lipid metabolism, although statins are the drug of choice for this.
More recently, pioglitazone and other active TZDs have been shown to bind to the outer mitochondrial membrane protein mitoNEET with affinity comparable to that of pioglitazone for PPAR.

# Indications and usage
Pioglitazone is used for the treatment of diabetes mellitus type 2 (non-insulin-dependent diabetes mellitus, NIDDM) in monotherapy but usually in combination with sulfonylurea, metformin, or insulin.  Pioglitazone has also been used to treat non-alcoholic steatohepatitis (fatty liver), but this use is presently considered experimental.

# 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 also admitted that pioglitazone has similar implications for female patients.
The risk of hypoglycemia is low in the absence of other drugs that lower blood glucose.
Like other thiazolidinediones, 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 a slightly increased proportion of upper respiratory tract infection, sinusitis, headache, myalgia and tooth problems.
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". The FDA Advisory Committee are currently (as of 2007) reviewing rosiglitazone data following an initial rejection of submitted data. Pioglitazone was not reviewed. A meta-analysis released subsequently showed that pioglitazone reduced the number of ischemic cardiac events rather than increase the risk.

# Drug interactions
Sulfonamides, metformin, and insulin reciprocally exponentiate hypoglycemia. Therapy with pioglitazone increased risk for pregnancy in those taking oral contraception.

# How supplied
Pioglitazone as Actos is supplied in oral tablets containing 15, 30 or 45 mg of pioglitazone base. It is also available in combination with metformin as ActoplusMet (tablets containing 15 mg pioglitazone and either 500 or 850 mg of metformin) or in combination with Amaryl as Duetact (tablets containing 30 mg pioglitazone and either 2 or 4 mg of Amaryl).