Pioglitazone with metformin

How it works

Pioglitazone activates PPAR-gamma to enhance peripheral insulin sensitivity, while metformin reduces hepatic glucose production and also improves insulin sensitivity.

Prescribing in practice

• Pioglitazone causes fluid retention and is contraindicated in heart failure or a history of it, and the metformin component adds the risk of lactic acidosis in renal impairment or acute illness.
• Pioglitazone is associated with an increased risk of bladder cancer and of fractures, so it should be avoided in active or previous bladder cancer or uninvestigated haematuria, and benefit reviewed periodically.
• Hypoglycaemia is unlikely with these agents alone but more likely when combined with a sulfonylurea or insulin.

Monitoring

Monitor HbA1c, weight and signs of fluid retention or heart failure, liver function, and renal function for the metformin component.

Counselling the patient

• Report any swelling of the ankles, breathlessness or rapid weight gain, which may indicate fluid retention.
• Report visible blood in the urine or new urinary symptoms.
• Take with food to reduce stomach upset and continue diet and exercise alongside the medicine.

Evidence & guidelines

Pioglitazone-metformin combinations feature in NICE type 2 diabetes guidance as an option for further glycaemic control, balanced against pioglitazone's recognised risks of heart failure, fractures and bladder cancer.