PJ Online | POEM | Metformin-induced lactic acidosis is extremely rare

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The Pharmaceutical Journal Vol 272 No 7292 p374 27 March 2004	This article Reprint Photocopy
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POEM (Patient-Oriented Evidence that Matters)

Metformin-induced lactic acidosis is extremely rare
POEM series

Clinical question What is the risk of lactic acidosis accompanying metformin therapy in patients with type 2 diabetes?

Bottom line The link between metformin and lactic acidosis, when used as prescribed, is tenuous. The bigger question is whether lactic acidosis risk truly increases when we relax criteria over who can take it.

Synopsis It is tricky to try to prove the non-existence of a phenomenon. The adage holds: absence of proof is not proof of absence. So, how much absence of proof do we need? The authors of this study combined the results of all randomised controlled trials and observational studies to determine the risk of lactic acidosis with metformin. The literature search was thorough and included unpublished data. Two independent reviewers evaluated articles for inclusion. The methodological quality of the studies was evaluated using modified quality criteria. Of the 194 studies in the analysis, 126 were randomised controlled studies and 68 were observational research. More than 18,000 participants in these studies received metformin for an average of 2.1 years (36,893 patient-years). There were no cases of lactic acidosis in the metformin-treated group or in the comparison group. Not surprising, since patients with risk factors for lactic acidosis were undoubtedly not enrolled in any of the studies, and monitoring was more intense than in typical practice. Population studies estimate the rate of lactic acidosis to be between two and nine cases per 100,000 patient-years (which is also the rate of lactic acidosis in people with diabetes not receiving metformin). Using these numbers, one to three cases of lactic acidosis would have been expected in the current study. Several studies evaluated lactic acid levels in metformin-treated patients, finding no difference in baseline lactic acid levels compared with those not treated with metformin.

Level of evidence 1a (systematic review, with homogeneity, of randomised controlled trials).

Reference Salpeter SR, Greyber E, Pasternak GA, Salpeter EE. Risk of fatal and nonfatal lactic acidosis with metformin use in type 2 diabetes mellitus. Archives of Internal Medicine 2003;163:2594