Pioglitazone: uses, monitoring and safety cautions

Pioglitazone is a thiazolidinedione. The emc product information lists it for adults with type 2 diabetes, on its own or with metformin, a sulfonylurea or insulin, and highlights people who are overweight and cannot take metformin. The NHS had no pioglitazone patient page available when checked, so this guide relies on the emc summary of product characteristics.

The mechanism differs from most other diabetes tablets. Instead of increasing insulin release, pioglitazone activates a nuclear receptor called PPAR gamma, which improves insulin sensitivity in liver, fat and muscle cells. Less glucose is released by the liver and more is taken up by tissues.

It is a once-daily oral tablet, with or without food. The SmPC describes starting at a lower dose and increasing in steps to a stated maximum, and says older adults should start at the lowest available strength. If it is added to insulin, the existing insulin dose is continued and reduced only if hypoglycaemia occurs. Glycaemic control is reviewed after several months and the benefit is reassessed at routine reviews.

The SmPC warns that pioglitazone can cause the body to hold on to fluid, which may bring on or worsen heart failure. The risk is greater in combination with insulin and in people with a previous heart attack, coronary disease or advanced age. Swelling of the ankles is the most frequently reported adverse effect, and rapid weight gain, breathlessness or swelling should be reported promptly.

Weight gain is dose related and may include both fat and fluid. A calorie-controlled eating pattern is advised alongside treatment. Because of the fluid effect, any history of heart failure is a firm contraindication.

An increased rate of bone fractures was seen in women but not men, so long-term fracture risk is considered. A small increase in bladder cancer cases was reported in analyses, so risk factors such as age, smoking and past chemotherapy are assessed before treatment, and visible blood in urine should be investigated first.

There are post-marketing reports of new or worse diabetic macular oedema, so tell your clinician about vision changes. Rare liver dysfunction has been reported; baseline liver enzymes are checked, monitored periodically, and treatment stops if enzymes remain markedly raised or jaundice appears.

The SmPC lists oedema as very common, and as common: upper respiratory infection, anaemia, headache, dizziness, reduced sensation, breathlessness, joint and back pain, bone fractures, weight increase, erectile dysfunction and blood in urine. Hypoglycaemia is common when combined with a sulfonylurea or insulin. Uncommon effects include sinusitis, bladder cancer, increased appetite, visual disturbance and fatigue. Allergic reactions, macular oedema and raised liver enzymes have unknown frequency.

• Seek urgent help for breathlessness, rapid swelling, jaundice or signs of an allergic reaction.

• Report visible blood in your urine to your doctor promptly.

Gemfibrozil, which inhibits the CYP2C8 enzyme, roughly triples exposure to pioglitazone, so a lower dose may be needed. Rifampicin, an enzyme inducer, lowers levels, so a higher dose may be needed. The SmPC reports no relevant interactions with digoxin, warfarin, metformin, oral contraceptives, ciclosporin, calcium channel blockers or statins.

Pioglitazone should not be used in pregnancy or breastfeeding. In people with polycystic ovary syndrome it may restore ovulation, so contraception matters. Driving is not usually affected unless vision changes occur. It is a prescription-only medicine, with generic products from several UK suppliers listed on emc.