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Thiazolidinedione + biguanide Pregnancy: Must not be used during pregnancy — discontinue if pregnancy occurs. Not recommended in women of childbearing potential not using contraception; discontinue if a patient wishes to conceive. Contraindicated in breast-feeding (§4.3, §4.6).

Pioglitazone with metformin

Brand names: Competact

Used in: Diabetes & DKA

A fixed-dose oral combination of the thiazolidinedione pioglitazone and the biguanide metformin, used to improve glycaemic control in adults with type 2 diabetes, particularly where insulin resistance is prominent.

Auto-extracted from the source labelling — not yet independently clinician-verified. These values were distilled from the UK SPC (or the US label where noted) but have not had a clinician sign-off. Confirm against the current SmPC before prescribing.

Adult dose

Dose: Pioglitazone 30 mg/day plus metformin hydrochloride 1,700 mg/day — achievable with one tablet of the 15 mg/850 mg fixed-combination (Competact), taken twice a day
Route: Oral
Frequency: Twice daily
Source: UK SPC §4.2 for Competact 15 mg/850 mg film-coated tablets. Stated for adults with normal renal function (GFR >= 90 mL/min). Dose titration with pioglitazone (added to the optimal dose of metformin) should be considered before switching the patient to the fixed combination; when clinically appropriate, direct change from metformin monotherapy may be considered. Tablets should be swallowed with a glass of water; taking with, or just after, food may reduce metformin-related GI symptoms. Elderly: monitor renal function regularly; start at the lowest available dose and increase gradually, particularly when pioglitazone is used with insulin. Hepatic impairment: should not be used. Paediatric: safety and efficacy in children and adolescents under 18 years have not been established — no data available. eMC §4.5 (interactions) was not captured in this bundle — clinician to check the full interaction list against the current SPC.

Dose adjustments

Renal

Assess GFR before initiation and at least annually thereafter (every 3–6 months if at increased risk of progression or elderly). GFR 60–89 mL/min: metformin maximum daily dose 3,000 mg (reduction may be considered as renal function declines); pioglitazone no adjustment, maximum daily dose 45 mg. GFR 45–59 mL/min: metformin maximum daily dose 2,000 mg, starting dose at most half the maximum. GFR 30–44 mL/min: metformin maximum daily dose 1,000 mg, starting dose at most half the maximum. GFR < 30 mL/min: metformin contraindicated. Maximum daily metformin dose should preferably be divided into 2–3 daily doses; if no adequate strength of the fixed combination is available, use the individual monocomponents.

Dose auto-extracted from UK Summary of Product Characteristics (SPC) via the eMC; US FDA prescribing information (openFDA / DailyMed) — cross-check; US labelling may differ from UK — not yet clinician-verified. Always confirm against the product SmPC and your local formulary before prescribing.

Contraindications

  • Hypersensitivity to the active substances or to any of the excipients
  • Cardiac failure or history of cardiac failure (NYHA stages I to IV)
  • Current bladder cancer or a history of bladder cancer
  • Uninvestigated macroscopic haematuria
  • Acute or chronic disease which may cause tissue hypoxia (e.g. cardiac or respiratory failure, recent myocardial infarction, shock)
  • Hepatic impairment
  • Acute alcohol intoxication, alcoholism
  • Any type of acute metabolic acidosis (e.g. lactic acidosis, diabetic ketoacidosis); diabetic pre-coma
  • Severe renal failure (GFR < 30 mL/min)
  • Acute conditions with the potential to alter renal function: dehydration, severe infection, shock, intravascular administration of iodinated contrast agents
  • Breast-feeding

Side effects

  • Very common: abdominal pain, diarrhoea, loss of appetite, nausea, vomiting (usually settle spontaneously)
  • Common: bone fracture, weight increase, oedema
  • Common: vitamin B12 decrease/deficiency; upper respiratory tract infection; headache; taste disturbance
  • Uncommon: bladder cancer; sinusitis
  • Very rare: lactic acidosis (serious — acidotic dyspnoea, abdominal pain, muscle cramps, asthenia, hypothermia followed by coma)
  • Not known: hypersensitivity/allergic reactions including anaphylaxis and angioedema; hepatitis; macular oedema

Interactions

  • Intravascular iodinated contrast agents — contraindicated (§4.3)
  • Medicinal products that can acutely impair renal function (antihypertensives, diuretics, NSAIDs) — initiate with caution in metformin-treated patients (§4.4)
  • Excessive alcohol intake / acute alcohol intoxication — increases risk of lactic acidosis (§4.3, §4.4)
  • Concomitant medicinal products that may themselves cause lactic acidosis — increased risk (§4.4)
  • eMC §4.5 not captured in this bundle; the US pioglitazone-only label states strong CYP2C8 inhibitors (e.g. gemfibrozil) increase pioglitazone exposure ~3-fold (limit pioglitazone to 15 mg daily), and CYP2C8 inducers (e.g. rifampicin) and topiramate reduce pioglitazone exposure — verify against the current UK SPC

Clinical monograph

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.

Reference: NICE NG28; Drug verified in RxNorm (NLM); confirm dosing against the manufacturer SPC (eMC). Verify against your local formulary and current prescribing references before prescribing. The structured dose values shown have been reviewed by a clinician. Monograph status: clinician-reviewed (2026-07-04).

Related

Curated clinical cross-links plus same-class fallbacks.

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