Metformin Hydrochloride / Pioglitazone

What it is and how it works

Metformin decreases hepatic glucose production, reduces intestinal glucose absorption and improves peripheral insulin sensitivity. Pioglitazone is a PPAR-gamma agonist that increases insulin sensitivity in adipose tissue, skeletal muscle and liver; the two act complementarily to lower blood glucose.

Indications

Type 2 diabetes mellitus in adults, particularly overweight patients, not adequately controlled on metformin alone or already treated with both drugs as separate tablets.

Dosage and administration (summary)

Usually 1 tablet (pioglitazone 15 mg / metformin 850 mg) orally twice daily with or just after meals, based on the patient’s current doses; maximum pioglitazone 45 mg daily.

Contraindications

Cardiac failure or history of cardiac failure; current or history of bladder cancer or uninvestigated macroscopic haematuria; hepatic impairment; severe renal impairment (eGFR below 30 mL/min); diabetic ketoacidosis; acute conditions that may cause tissue hypoxia or alter renal function (dehydration, severe infection, shock, recent myocardial infarction, respiratory failure); acute alcohol intoxication or alcoholism.

Warnings and precautions

Pioglitazone causes fluid retention and may precipitate heart failure; monitor for weight gain and oedema, especially with insulin. Lactic acidosis from metformin is rare but serious; stop before iodinated contrast and major surgery and monitor renal function. Increased fracture risk (particularly in women), macular oedema, liver dysfunction and a possible small increased risk of bladder cancer have been reported with pioglitazone.

Pregnancy

Should not be used in pregnancy; insulin is preferred.

Storage and supply

Store below 25–30 °C.

Source: reference summary prepared from the EU SmPC/EPAR, BNF and WHO Model Formulary. The approved product information in Iran governs.