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Metformin and lactic acidosis

Last reviewed dd mmm yyyy. Last edited dd mmm yyyy

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Metformin is a biguanide oral hypoglycaemic which suppresses appetite.

Metformin is first-line drug treatment for overweight patients with type 2 diabetes (1) in whom diet and exercise treatments have failed.

The principle advantage of metformin treatment is that glycaemic control is improved but with significantly less weight gain than when sulphonylureas are used (2).

It is unlikely to cause hypoglycaemia.

Metformin is contraindicated if there is liver, kidney or heart failure, or in patients with a very high alcohol intake because of the perceived risk of serious lactic acidosis.

  • however studies by Salpeter et al concluded that the use of metformin in type 2 diabetes does not increase the risk for fatal or non-fatal lactic acidosis or increase in blood lactate concentrations compared with placebo or other hypoglycaemic treatments (3,4)
    • a commentary in the Evidence Based Medicine journal concerning this study stated...'in contrast to phenformin, no credible evidence exists that metformin increases the risk for lactic acidosis beyond what would be expected from underlying diseases' (5)
  • this gap between evidence and prescribing guidelines makes management decisions difficult for the clinician - a clinician must therefore make decisions in the context of evidence, his or her own clinical experience and expertise in this area, prescribing guidelines and the summary of product characteristics
  • metformin is primarily a type B lactic acidosis
    • however, the lactic acidosis can be compounded by type A when the drug's lactic acid accumulation leads to cardiovascular collapse, tissue hypoperfusion, and hepatic dysfunction
    • estimated incidence is 6 cases per 100,000 patient-years (7)

Note that NICE guidance (6) states that:

  • review the dose of metformin if the serum creatinine exceeds 130 micromol/litre or the estimated glomerular filtration rate (eGFR) is below 45 ml/minute/1.73-m2.
  • stop the metformin if the serum creatinine exceeds 150 micromol/litre or the eGFR is below 30 ml/minute/1.73-m2

The summary of product characteristics should be consulted before prescribing this drug.

Reference:

  1. Lancet (1998), 352, 854-65.
  2. Prescribers' Journal (2000), 40 (1), 38-48
  3. Salpeter S et al (2002). Risk of fatal and nonfatal lactic acidosis with metformin use in type 2 diabetes. Cochrane Database Syst Reve: CD002967 (latest version 27 Feb 2002).
  4. Salpeter S et al (2003). Risk of fatal and nonfatal lactic acidosis with metformin use in type 2 diabetes mellitus: systematic review and meta-analysis. Arch Intern Med 2003;163:2594-602.
  5. Evidence based Medicine (2002), 7(6),176.
  6. NICE (May 2008). Management of type 2 diabetes.
  7. Blough B, Moreland A, Mora A Jr. Metformin-induced lactic acidosis with emphasis on the anion gap. Proc (Bayl Univ Med Cent). 2015 Jan;28(1):31-3.

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