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First line agent to treat type 2 diabetes and prediabetes
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Biguanide that decreases peripheral insulin resistance and hepatic gluconeogenesis
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Reduces cardiovascular disease independent of glycaemic control
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Often leads to mild weight loss
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Hypoglycaemia on metformin alone is extremely rare
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Maximum dose of 3 g per day
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Little therapeutic benefit and greater risk of adverse effects for doses > 2 g per day
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Start at 250 - 500 mg od or bd and uptitrate weekly to 2 g/day or maximal tolerated dose with food
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Starting low and slow typically avoids adverse effects even in those previously ‘intolerant’
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Adverse effects of metformin include:
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Nausea, abdominal pain, vomiting and diarrhoea (common but often transient)
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Metallic taste in mouth
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Lactic acidosis (rare)
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Mild reduction in serum vitamin B12 levels but B12 deficiency is rare.
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N.B. Consider starting metformin with second agent in any person with newly diagnosed diabetes if HbA1c > 64 mmol/mol e.g.:
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If cardiovascular and/or renal disease → preferably SGLT2i or GLP1RA
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If heart failure → preferably SGLT2i
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If no cardiovascular disease, renal disease or heart failure → preferably DPPIVi
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Reduce doses in renal impairment and contraindicated in renal, liver and heart failure
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eGFR < 15 mL/min – metformin is contraindicated
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eGFR 15 – 29 mL/min – maximum daily dose 500 mg
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eGFR 30 – 59 mL/min – maximum daily dose 1000 mg
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If worsening neuropathy on metformin then check serum vitamin B12 levels
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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)