Pioglitazone

Products

Pioglitazone is commercially available in tablet form (Actos, generics). It is also available as a fixed-dose combination with metformin (Competact). Pioglitazone has been approved in many countries since 2000.

Structure and properties

Pioglitazone (C19H20N2O3S, Mr = 356.4 g/mol) belongs to the thiazolidinediones. It is present in drugs as a racemate and as pioglitazone hydrochloride, an odorless, white, crystalline powder that is practically insoluble in water.

Effects

Pioglitazone (ATC A10BG03) has antidiabetic and antihyperglycemic properties, normalizes blood glucose, and lowers HbA1c. It is a high-affinity agonist at the nuclear receptor PPAR-γ, which controls the regulation of genes involved in glucose and lipid metabolism. Its effects are primarily due to increased sensitivity of adipose tissue, muscle, and liver to insulin, thus decreasing insulin resistance and increasing uptake of blood glucose into tissues. Unlike sulfonylureas, pioglitazone does not promote insulin secretion.

Indications

As a 2nd-line agent for the treatment of type 2 diabetes. Treatment duration should not usually exceed 2 years.

Dosage

According to the SmPC. Tablets are taken once daily with or without food.

Contraindications

  • Hypersensitivity
  • Diabetes mellitus type 1
  • Heart failure NYHA III and IV
  • Moderate to severe hepatic insufficiency
  • Diabetic ketoacidosis
  • Pregnancy and lactation
  • Bladder cancer or bladder cancer in the patient history.
  • Unexplained hematuria

For complete precautions, see the drug label.

Interactions

Pioglitazone is metabolized by CYP2A1, CYP3A4, CYP2C8, and CYP2C9. Interactions are possible with NSAIDs, gemfibrozil (CYP2C8 inhibitor), and rifampicin (CYP inducer).

Adverse effects

The most common possible adverse effects include muscle, joint, and back pain; difficulty breathing; digestive problems; dental problems; weight gain; upper respiratory tract infections; headache; sensory disturbances; visual disturbances; fatigue; and insomnia. Hypoglycemia is frequently observed in combination with sulfonylureas and insulins. Occasionally, the development of bladder cancer is to be expected. Therefore, the duration of treatment has been limited to a maximum of two years.