Metformin

Metformin

Metformin is a biguanide used mainly in the treatment of type 2 diabetes mellitus. It has a number of actions which improves glucose tolerance (see below). Unlike sulphonylureas it does not cause hypoglycaemia and weight gain and is therefore first-line, particularly if the patient is overweight. Metformin is also used in polycystic ovarian syndrome and non-alcoholic fatty liver disease

Mechanism of action

• acts by activation of the AMP-activated protein kinase (AMPK)
  Metformin acts by activation of the AMP-activated protein kinase (AMPK)
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  Importance: 71
• increases insulin sensitivity
  Metformin is a biguanide that reduces hepatic gluconeogenesis and reduces insulin resistance
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  Importance: 34
• decreases hepatic gluconeogenesis
  Metformin is a biguanide that reduces hepatic gluconeogenesis and reduces insulin resistance
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  Importance: 34
• may also reduce gastrointestinal absorption of carbohydrates

Adverse effects

• gastrointestinal upsets are common
  Gastrointestinal side-effects such as diarrhoea and bloating are a common side effect with metformin
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  Importance: 54
  (nausea, anorexia, diarrhoea), intolerable in 20%
• reduced vitamin B12 absorption
  reduced vitamin B12 absorption
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  - rarely a clinical problem
• lactic acidosis
  Although rare, lactic acidosis is an important side-effect of metformin
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  Importance: 64
  with severe liver disease or renal failure
  renal failure
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  • it is now increasingly recognised that lactic acidosis secondary to metformin is rare, although it remains important in the context of exams

Contraindications

• chronic kidney disease
  NICE recommend that the dose of metformin should be reviewed if the creatinine is > 130 micromol/l (or eGFR < 45 ml/min) and stopped if the creatinine is > 150 micromol/l (or eGFR < 30 ml/min)
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  Importance: 5
  : NICE recommend that the dose should be reviewed if the creatinine is > 130 µmol/l (or eGFR < 45 ml/min) and stopped if the creatinine is > 150 µmol/l (or eGFR < 30 ml/min
  eGFR < 30 ml/min
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  )
• metformin may cause lactic acidosis if taken during a period where there is tissue hypoxia. Examples include a recent myocardial infarction
  Metformin should be stopped temporarily following a myocardial infarction due to an increased risk of lactic acidosis
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  Importance: 20
  , sepsis, acute kidney injury and severe dehydration
• iodine-containing x-ray contrast media
  iodine-containing x-ray contrast media
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  :
  • there is a theoretical increased risk of provoking renal impairment due to contrast nephropathy
  • BNF guidance: metformin should be discontinued on the day of the procedure and for 48 hours thereafter
  • Royal College Radiology guidance (reflects modern evidence and UK radiology practice): cease metformin 48h before contrast media only if eGFR <30 or patient has deteriorating renal function
• alcohol abuse is a relative contraindication

Starting metformin

• metformin should be titrated up slowly
  Metformin should be titrated slowly, leave at least 1 week before increasing dose
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  Importance: 81
  to reduce the incidence of gastrointestinal side-effects
• if patients develop unacceptable side-effects then modified-release metformin should be considered
  If metformin is not tolerated due to GI side-effects, try a modified-release formulation before switching to a second-line agent
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  Importance: 49

+PassMedicine Notes

Metformin is a biguanide used mainly in the treatment of type 2 diabetes mellitus. It has a number of actions which improves glucose tolerance (see below). Unlike sulphonylureas it does not cause hypoglycaemia and weight gain and is therefore first-line, particularly if the patient is overweight. Metformin is also used in polycystic ovarian syndrome and non-alcoholic fatty liver disease

Mechanism of action

• acts by activation of the AMP-activated protein kinase (AMPK)
• increases insulin sensitivity
• decreases hepatic gluconeogenesis
• may also reduce gastrointestinal absorption of carbohydrates

Adverse effects

• gastrointestinal upsets are common (nausea, anorexia, diarrhoea), intolerable in 20%
• reduced vitamin B12 absorption - rarely a clinical problem
• lactic acidosis with severe liver disease or renal failure
• it is now increasingly recognised that lactic acidosis secondary to metformin is rare, although it remains important in the context of exams

Contraindications

• chronic kidney disease: NICE recommend that the dose should be reviewed if the creatinine is > 130 µmol/l (or eGFR < 45 ml/min) and stopped if the creatinine is > 150 µmol/l (or eGFR < 30 ml/min)
• metformin may cause lactic acidosis if taken during a period where there is tissue hypoxia. Examples include a recent myocardial infarction, sepsis, acute kidney injury and severe dehydration
• iodine-containing x-ray contrast media:
• there is a theoretical increased risk of provoking renal impairment due to contrast nephropathy
• BNF guidance: metformin should be discontinued on the day of the procedure and for 48 hours thereafter
• Royal College Radiology guidance (reflects modern evidence and UK radiology practice): cease metformin 48h before contrast media only if eGFR