PIOGLITAZONE

'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.

Contents

Pharmacology

Indications and Usage

Contraindications

Side effects

Drug interactions

How supplied

See also

References

External links

Pharmacology

Pioglitazone selectively stimulates nuclear receptor peroxisone proliferator-activated receptor gamma (PPARγ). 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. Pioglitazone does not directly stimulate insulin secretion, but rather affects the insulin-synthetic function of the pancreas. Pioglitazone also 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 has been shown to bind to the outer mitochondrial membrane protein mitoNEET with affinity comparable to that of pioglitazone for PPARγ.^[1][2]

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.^[3]

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.[3] The information was based on data from the ADOPT trial.[4] 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 pioglitazone for the treatment of type 2 diabetes was associated with a greater risk of "myocardial ischemic events" (from the proactive study and in a joint study with rosiglitazone. The FDA Advisory Committee are currently reviewing pioglitazone data following an initial rejection of submitted data.

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, however it should be noted that 15 mg is a subtherapeutic dose, with 30 mg the starting dose. It is also available in combination with metformed as ActoplusMet® (tablets containing 15 mg pioglitazone and either 500 or 850 mg of metformin).

See also

★ Anti-diabetic drugs

★ Thiazolidinedione

References

1. Identification of a novel mitochondrial protein ("mitoNEET") cross-linked specifically by a thiazolidinedione photoprobe, Colca JR, McDonald WG, Waldon DJ, Leone JW, Lull JM, Bannow CA, Lund ET, Mathews WR, , , Am. J. Physiol. Endocrinol. Metab., 2004
2. MitoNEET is a uniquely folded 2Fe 2S outer mitochondrial membrane protein stabilized by pioglitazone, Paddock ML, Wiley SE, Axelrod HL, Cohen AE, Roy M, Abresch EC, Capraro D, Murphy AN, Nechushtai R, Dixon JE, Jennings PA, , , Proc. Natl. Acad. Sci. U.S.A., 2007
3. A placebo-controlled trial of pioglitazone in subjects with nonalcoholic steatohepatitis, Belfort R, Harrison SA, Brown K, ''et al.'', , , , 2006

External links

★ Official site

★ Pioglitazone FAQ