First line agent to treat type 2 diabetes and prediabetes
Biguanide that decreases peripheral insulin resistance and hepatic gluconeogenesis
Reduces cardiovascular disease independent of glycaemic control
Often leads to mild weight loss
Hypoglycaemia on metformin alone is extremely rare
Maximum dose of 3 g per day
Little therapeutic benefit and greater risk of adverse effects for doses > 2 g per day
Start at 250 - 500 mg od or bd and uptitrate weekly to 2 g/day or maximal tolerated dose with food
Starting low and slow typically avoids adverse effects even in those previously ‘intolerant’
Adverse effects of metformin include:
Nausea, abdominal pain, vomiting and diarrhoea (common but often transient)
Metallic taste in mouth
Lactic acidosis (rare)
Mild reduction in serum vitamin B12 levels but B12 deficiency is rare.
N.B. Consider starting metformin with second agent in any person with newly diagnosed diabetes if HbA1c > 64 mmol/mol e.g.:
If cardiovascular and/or renal disease → preferably SGLT2i or GLP1RA
If heart failure → preferably SGLT2i
If no cardiovascular disease, renal disease or heart failure → preferably DPPIVi
Reduce doses in renal impairment and contraindicated in renal, liver and heart failure
eGFR < 15 mL/min – metformin is contraindicated
eGFR 15 – 29 mL/min – maximum daily dose 500 mg
eGFR 30 – 59 mL/min – maximum daily dose 1000 mg*
*NB: International guidelines (e.g. KDIGO) now recommend that a metformin dose of 2 g per day is safe when the eGFR is > 45 mL/min. Therefore, although 'off-label', best practice is now not to reduce the dose of metformin for renal dysfunction until the eGFR is < 45 mL/min. For more information on responsibilities when prescribing for an 'off-label' use please click here .
If worsening neuropathy on metformin then check serum vitamin B12 levels
If introduced to a regimen with insulin and/or sulfonylureas, then the dose of insulin and/or sulfonylureas may need to be reduced to prevent hypoglycaemia (particularly if the HbA1c is < 64 mmol/mol)
