Pioglitazone/metformin

Pioglitazone/metformin (also known by the brand names Actoplus Met, Piomet and Politor) is combination of two oral diabetes medications pioglitazone and metformin. The two oral antihyperglycemic agents with different mechanisms of action are used to improve glycemic control in patients with diabetes mellitus type 2.

Mechanisms

• Pioglitazone is a member of the thiazolidinedione class, it decreases insulin resistance in the periphery and in the liver resulting in increased insulin dependent glucose disposal and decreased hepatic glucose output.
• Metformin is a member of the biguanide class, improves glucose tolerance in patients with type 2 diabetes, lowering both basal and postprandial plasma glucose. Metformin decreases hepatic glucose production, decreases intestinal absorption of glucose and improves insulin sensitivity by increasing peripheral glucose uptake and utilization.

Indication

Pioglitazone/metformin is indicated as an adjunct to diet and exercise:

• To improve glycemic control in patients with type 2 diabetes, or
• For patients who are already treated with a separate combination of pioglitazone and metformin,
• For patients whose diabetes is not adequately controlled with metformin alone, or
• For patients who have initially responded to pioglitazone alone and require additional glycemic control.

Dosage and administration

Recommended dose

Use of antihyperglycemic agents in the management of type 2 diabetes should be individualized on the basis of effectiveness and tolerability.

Pioglitazone/metformin should be given with meals; the initial starting dose is either the 15 mg/500 mg or 15 mg/850 mg tablet strength once or twice daily, and gradually titrated after assessing adequacy of therapeutic response, while not exceeding the maximum recommended daily dose of pioglitazone 45 mg and metformin 2550 mg.

Starting dose for patients who initially responded to pioglitazone monotherapy and require additional glycemic control: Based on the usual starting doses of metformin (500 mg twice daily or 850 mg daily), pioglitazone/metformin may be initiated at either the 15 mg/500 mg twice daily or 15 mg/85 mg once daily, and gradually titrated after assessing adequacy of therapeutic response.

Starting dose for patients inadequately controlled on metformin monotherapy: Based on the usual starting dose of pioglitazone (15–30 mg daily), pioglitazone/metformin may be initiated at either the 15 mg/500 mg or 15 mg/850 mg once or twice daily, and gradually titrated after assessing adequacy of therapeutic response.

Starting dose for patients switching from combination therapy of pioglitazone plus metformin as separate tablets: pioglitazone/metformin may be initiated with either the 15 mg/500 mg or 15 mg/850 mg tablet strengths based on the dose of pioglitazone and metformin already being taken.

Use in pregnancy and lactation

Pioglitazone/metformin should not be used during pregnancy unless the potential benefit justifies the potential risk to the fetus. There are no adequate and well-controlled studies in pregnant women with combination of pioglitazone and metformin or its individual components. It is not known whether pioglitazone and/or metformin are secreted in human milk. Because many drugs are excreted in human milk, pioglitazone/metformin should not be administered to a breastfeeding woman.

Precautions

Pioglitazone/metformin should not be used in patients with type I diabetes or for the treatment of diabetic ketoacidosis and should be used with caution in patients with edema. Serum ALT levels should be evaluated prior to the initiation of therapy with combination of pioglitazone and metformin in all patients and periodically thereafter per the clinical judgment of the health care professional.

Side-effects

The most common side-effects are upper respiratory tract infection, diarrhea, combined edema/peripheral edema and headache, respectively. Most clinical adverse events were similar between groups treated with pioglitazone in combination with metformin and those treated with pioglitazone monotherapy.

Contraindications

Pioglitazone/metformin is contraindicated in patients with known hypersensitivity to any components of this combination. These combination also contraindicated in renal disease which may also result from conditions, e.g., acute myocardial infarction, septicemia, acute or chronic metabolic acidosis, including diabetic ketoacidosis, with or without coma.

Drug interaction

Pioglitazone/metformin may interact with furosemide, nifedipine, cationic drugs (e.g., amiloride, digoxin, morphine, procainamide, quinidine, quinine, ranitidine, triamterene, trimethoprim, and vancomycin) and certain drugs tend to produce hyperglycemia and may lead to loss of glycemic control (e.g., thiazides and other diuretics, corticosteroids, phenothiazines, thyroid products, estrogens, oral contraceptives, phenytoin, nicotinic acid, sympathomimetics, calcium channel blocking drugs, and isoniazid).

References