Understanding the association between metformin plasma concentrations and lactate
Abstract
There is considerable confusion about the safe dosing of metformin in patients with renal impairment. Metformin has traditionally been contraindicated in this patient group due to the concern that reduced metformin elimination would lead to elevated plasma concentrations and an increased risk of hyperlactatemia and associated acidosis. Recent changes to published guidelines propose that metformin can be used in renally impaired patients provided that doses are reduced. Unfortunately, the dosing guidelines show little agreement, and few appear to be evidence-based. This leaves prescribers with inconsistent messages concerning the safe dosing of metformin and a poor understanding of risk mitigation. In theory, metformin dose adjustment along with metformin plasma concentration monitoring will ensure that concentrations do not exceed the upper limit of safety in renally impaired patients and may therefore help mitigate the risk of hyperlactatemia and possibly acidosis. To date, however, a therapeutic range for metformin plasma concentrations has not been well defined. Using data extracted from the published literature, we aimed to understand the relationship between plasma metformin and lactate concentrations and to establish the metformin plasma concentration associated with severe hyperlactatemia (lactate >5 mmol/L). In this work, plasma lactate concentrations are used as a marker of lactic acidosis risk. The metformin concentration associated with severe hyperlactatemia is…
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