BRAND NAMES
 MECHANISM OF ACTION
Pioglitazone is a member of the thiazolidinedione class, it acts primarily by reducing insulin resistance in muscle and adipose tissue and by inhibiting hepatic gluconeogenesis. Pioglitazone is an agonist for peroxisome proliferator-activated receptor-gamma (PPARγ). PPAR receptors are found in tissues important for insulin action such as adipose tissue, skeletal muscle, and liver. Activation of PPARγ nuclear receptors modulates the transcription of a number of insulin responsive genes involved in the control of glucose and lipid metabolism.
Pioglitazone is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus in monotherapy and in combination with a sulfonylurea, metformin (Actoplus met), alogliptin (Oseni) or insulin.
Pioglitazone exerts its antihyperglycemic effect only in the presence of insulin. Therefore, it should not be used in patients with type 1 diabetes or for the treatment of diabetic ketoacidosis.
- The recommended starting dose for patients without congestive heart failure is 15 mg or 30 mg once daily without regard to meals
- The recommended starting dose for patients with congestive heart failure (NYHA Class I or II) is 15 mg once daily without regard to meals.
The dose can be titrated in increments of 15 mg up to a maximum of 45 mg once daily based on glycemic response as determined by HbA1c.
- Hypersensitivity to Pioglitazone
- Cardiac failure (NYHA Class III or IV). Pioglitazone can cause fluid retention, which may exacerbate or precipitate heart failure.
- Congestive Heart Failure: Pioglitazone, like other thiazolidinediones, can cause dose-related fluid retention when used alone or in combination with other antidiabetic medications, especially with insulin. Fluid retention may lead to or exacerbate congestive heart failure. Patients should be observed for signs and symptoms of congestive heart failure. If congestive heart failure develops, it should be managed according to current standards of care and discontinuation or dose reduction of pioglitazone must be considered
- Measure liver enzymes promptly in patients who report symptoms that may indicate liver injury, including fatigue, anorexia, right upper abdominal discomfort, dark urine or jaundice. (Because of postmarketing reports of fatal and non-fatal hepatic failure)
- Fractures: Increased incidence in female patients.
- Bladder Cancer: Available epidemiological data suggest a small increased risk of bladder cancer in diabetic patients treated with pioglitazone in particular in patients treated for the longest durations and with the highest cumulative doses. A possible risk after short term treatment cannot be excluded. For this reason both France and Germany have withdrawn pioglitazone products from the market.
- Macular edema has been reported in postmarketing experience in diabetic patients who were taking pioglitazone or another thiazolidinedione, therefore patients should have regular eye exams by an ophthalmologist
- Ovulation: Therapy with pioglitazone, like other thiazolidinediones, may result in ovulation in some premenopausal anovulatory women. Adequate contraception in all premenopausal women is recommended.
- Gemfibrozil (an inhibitor of CYP2C8) increases Pioglitazone exposure approximately 3-fold
- A lower dose of Insulin secretagogue, (e.g., sulfonylurea) or insulin when used in combination with Pioglitazone may be required to minimize the risk of hypoglycemia
 PREGNANCY AND LACTATION
- Pregnancy Category C (US), Pioglitazone should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
- In nursing mothers a decision should be made to discontinue nursing or discontinue Pioglitazone, taking into account the importance of the drug to the mother.
 SIDE EFFECTS
Possible side effects include: weight increase, visual disturbance, upper respiratory tract infection and insomnia
Serious adverse reactions: Congestive heart failure, Edema, Fractures and bladder cancer (See Precautions)
 RELATED LINKS
|Diabetes (Antidiabetic drugs)|
|Insulin Secretagogues (drugs that increase insulin release from pancreas)||Sulfonylureas||Chlorpropamide (Diabinese) • Glibenclamide or Glyburide (Diabeta, Micronase, Glynase, Daonil, Euglycon) • Gliclazide (Diamicron) • Glimepiride (Amaryl, Solosa) • Glipizide (Glucotrol, Minidiab, Glibenese) • Gliquidone (Glurenorm)|
|Meglitinides||Repaglinide (Prandin, Novonorm) • Nateglinide (Starlix)|
|Dipeptidyl peptidase-4 inhibitors||Linagliptin (Trajenta) • Saxagliptin (Onglyza) • Sitagliptin (Januvia) • Vildagliptin (Galvus)|
|Incretin mimetics (GLP-1 agonists and analogs)||Exenatide (Byetta) • Liraglutide (Victoza) • Lixisenatide (Lyxumia) • Dulaglutide (Trulicity)|
|Insulin Sensitizers (drugs that decrease insulin resistance)|
|Drugs that retard the digestion and absorption of carbohydrates in the small intestine|
|Alpha-glucosidase inhibitors||Acarbose (Glucobay, Precose)|
|Drugs that reduce glucose absorption in the kidney and increase glucose excretion in the urine|
|Sodium glucose cotransporter 2 (SGLT2) inhibitors||Canagliflozin (Invokana) • Dapagliflozin (Farxiga) • Empagliflozin (Jardiance, Glyxambi, Synjardi)|
|Insulin and insulin analogs|
|Intermediate acting insulins||Insulin lispro protamine (Humalog BASAL) • Isophane human insulin : Human insulin protamine (NPH) (Humulin I, Protaphane)|
|Long-acting insulins||Insulin detemir (Levemir) • Insulin glargine (Lantus)|
|Fast-acting insulins||Regular insulin : Insulin (Human recombinant) (Actrapid, Humulin R)|
|Ultra-rapid-acting insulins||Insulin aspart (Novorapid) • Insulin glulisine (Apidra) • Insulin lispro (Humalog) • Insulin human (Inhalation Powder) (Afrezza)|
|Premixed insulin (ultra-rapid-acting + intermediate acting||Insulin aspart / Insulin aspart protamine (Novomix) • Insulin lispro / Insulin lispro protamine (Humalog Mix)|
|Inhaled Insulin||Insulin human (Inhalation Powder) (Afrezza)|
|Sulfonylurea + Metformin||Glibenclamide / Metformin (Bieuglicon M, Diaglimet, Glibomet, Gliconorm, Glicorest, Suguan M)|
|Thiazolidinedione + Metformin||Pioglitazone / Metformin (Competact, Glubrava)|
|Thiazolidinedione + Sulfonylurea||Pioglitazone / Glimepiride (Tandemact)|
|Dipeptidyl peptidase-4 inhibitors + Metformin||Linagliptin / Metformin (Jentadueto) • Sitagliptin / Metformin (Efficib, Janumet, Velmetia) • Vildagliptin / Metformin (Eucreas)|