Metformin accumulation without hyperlactataemia and metformin-induced hyperlactataemia without metformin accumulation

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 (0.90 mmol/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 4.7 mmol/L during metformin therapy with daily doses of 2550, 1700 and 850 mg, respectively. After withdrawal, metformin was reintroduced for 5-day periods at 500 mg/day up to 2000 mg/day with washout intervals. Lactate concentration, normal at baseline, rapidly exceeded 2 mmol/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.