These case reports demonstrate that, at the individual level, blood metformin concentrations and metformin effects on lactate do not always correlate.

We report here on two unusual cases: metformin accumulation in the absence of hyperlactataemia; and metformin-induced hyperlactataemia with no metformin accumulation.

Patient #1 presented with severe kidney failure, severe acidosis (pH: 7.04), normal lactataemia (0.90mmol/L) and marked metformin accumulation. Patient #2 presented with hyperlactataemia, even after dose reduction, during otherwise well-tolerated metformin treatment. Arterial lactate levels were 8.8, 8.2 and 4.7mmol/L during metformin therapy with daily doses of 2550, 1700 and 850mg, respectively. After withdrawal, metformin was reintroduced for 5-day periods at 500mg/day up to 2000mg/day with washout intervals. Lactate concentration, normal at baseline, rapidly exceeded 2mmol/L after metformin administration.

These clinical data suggest a new concept for metformin therapy: there may be either resistance or, conversely, hypersensitivity to metformin effects on lactate generation according to the individual patient.