Lactic acidosis in metformin therapy: searching for a link with metformin in reports of ‘metformin‐associated lactic acidosis’
Abstract
SUMMARY Objective The link between metformin and lactic acidosis in metformin therapy may be causal, associated or coincidental. Our objective was to investigate this link by studying and analysing published reports of so‐called ‘metformin‐associated lactic acidosis’. Research design and methods systematically searched in the BIOSIS, DERWENT, EMBASE, MEDLINE, and PASCAL databases of the English language and non‐English language literature for all reports of so‐called ‘metformin‐associated lactic acidosis’ published from May 1995 through January 2000. We did not include reports related to metformin overdose or contrast media‐induced renal failure. Metformin accumulation and concurrent pathologies were critically reviewed as precipitating factors for metformin‐associated lactic acidosis. Metformin accumulation was assessed in terms of the recorded measurement of metformin concentration in plasma or, if not available, by the presence of primary renal failure, i.e. renal failure that was not secondary to a shock syndrome. Results We found 21 reports describing a total of 26 patients. Criteria of lactic acidosis (lactate > 5 mmol/l, pH ≤ 7.35) were not met in four patients. In the remaining 22 patients, plasma metformin concentration was determined in only four, of whom one had a normal value. In the 18 patients with lactic acidosis where plasma metformin concentration data was not available, the presence of primary renal failure was absent or unlikely in six patients, uncertain…
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