Thiazolidinedione (PPAR-γ Agonist) Pregnancy: Avoid — insufficient data; switch to insulin in pregnancy

Pioglitazone

Brand names: Actos

Adult dose

Dose: 15–30 mg OD, may increase to 45 mg OD after 4–8 weeks if needed

Route: Oral

Frequency: Once daily (with or without food)

Max: 45 mg OD

Useful in non-alcoholic fatty liver disease (NAFLD/NASH) and insulin resistance. PROACTIVE trial: improved CV outcomes in subset. Risk of bladder cancer with prolonged use — avoid if history of bladder cancer.

Paediatric dose

Route: N/A

Frequency: N/A

Max: Not licensed in children

Not established in paediatric patients

Dose adjustments

Renal

No dose adjustment required

Hepatic

Avoid in hepatic impairment (ALT >2.5× ULN)

Clinical pearls

Only licensed drug for NASH (alongside lifestyle) — PIVENS trial: improves steatosis and fibrosis
Avoid in heart failure — fluid retention worsens HF in all NYHA classes
Bladder cancer risk: counsel patients; annual urine dipstick; stop if haematuria occurs
Fracture risk: particularly in postmenopausal women — consider bone density assessment

Contraindications

Heart failure (any class)
History of bladder cancer
Haematuria under investigation
Hepatic impairment

Side effects

Fluid retention/oedema
Weight gain
Heart failure exacerbation
Fractures (especially women — upper limb, foot)
Bladder cancer risk (prolonged use, >2 years)
Macular oedema

Interactions

CYP2C8 inhibitors (gemfibrozil) — increase pioglitazone levels significantly
Insulin — additive fluid retention and hypoglycaemia risk

Monitoring

LFTs before start and periodically
Weight and signs of fluid retention
HbA1c
Urinalysis (haematuria)
Bone density in women on long-term therapy

Reference: BNFc; BNF; PROACTIVE Trial (Dormandy et al, Lancet 2005); PIVENS Trial (Sanyal et al, NEJM 2010). Verify against your local formulary and the latest BNF before prescribing.

Curated clinical cross-links plus same-class fallbacks.

Pathways