Metformin-induced lacticacidemia in patients with type 2 diabetes mellitus

To determine whether metformin therapy can predispose patients with type 2 diabetes and normal renal function to lactic acidosis when certain conditions are present.

We undertook this prospective cohort study in 110 consecutive patients (age range, 27 to 85 years) with normal serum creatinine levels (<1.5 mg/dL in men; <1.4 mg/dL in women), receiving metformin as monotherapy or in combination with sulfonylurea or insulin, who were undergoing assessment on a regular basis for diabetes care. Clinical evaluations were performed at 4- to 12-week intervals for up to 2 years. Serum electrolytes and creatinine as well as plasma lactic acid determinations were done in all patients, regardless of symptoms. The anion gap was calculated.

Plasma lactic acid concentrations were normal in 47 patients (mean, 9.4 +/- 18.0 mg/dL or 1.053 +/- 0.194 mmol/L) and high in 63 patients (19.63 +/- 5.11 mg/dL or 2.208 +/- 0.569 mmol/L; P<0.001). The anion gap was increased in the high lactic acid group in comparison with the normal group (P<0.001). Comorbid conditions (for example, cardiovascular or respiratory disease) that may predispose to hypoxemia or compromise tissue perfusion were significantly more prevalent in patients in the high lactic acid group than in those with normal lactic acid values.

Lacticacidemia may occur in metformin-treated patients with type 2 diabetes mellitus who have normal renal function. An increased anion gap and certain clinical symptoms may serve as clues for the presence of lacticacidemia. Progression from lacticacidemia to clinical lactic acidosis, under certain hemodynamic or respiratory adverse conditions, remains conjectural and needs further evaluation.