Combined metformin-associated lactic acidosis and euglycemic ketoacidosis

Abstract

Background: In renal failure metformin can lead to lactic acidosis. Additional inhibition of hepatic gluconeogenesis by accumulation of the drug may aggravate fasting-induced ketoacidosis. We report the occurrence of metformin-associated lactic acidosis (MALA) with concurrent euglycemic ketoacidosis (MALKA) in three patients with renal failure.

Case presentations: Patient 1: a 78-year-old woman (pH = 6.89, lactic acid 22 mmol/l, serum ketoacids 7.4 mmol/l and blood glucose 63 mg/dl) on metformin and insulin treatment. Patient 2: a 79-year-old woman on metformin treatment (pH = 6.80, lactic acid 14.7 mmol/l, serum ketoacids 6.4 mmol/l and blood glucose 76 mg/dl). Patient 3: a 71-year-old man on metformin, canagliflozin and liraglutide treatment (pH = 7.21, lactic acid 5.9 mmol/l, serum ketoacids 16 mmol/l and blood glucose 150 mg/dl). In all patients, ketoacidosis receded on glucose infusion and renal replacement therapy.

Conclusion: This case series highlights the parallel occurrence of MALA and euglycemic ketoacidosis, the latter exceeding ketosis due to starvation, suggesting a metformin-triggered inhibition of gluconeogenesis. Affected patients benefit from glucose infusion counteracting suppressed hepatic gluconeogenesis.

Keywords: Ketoacidosis; Lactic acidosis; Metformin; Type 2 diabetes.

Fig. 1

Metformin-associated lactic acidosis and euglycemic ketoacidosis in three critically ill patients. Blood gas analyses with serum levels of lactic acid (closed diamonds), ketoacids (0.00–8.00 mmol/l; closed squares), and base excess levels (open triangles) are plotted for patient 1 (a), patient 2 (b), and patient 3 (c) as a function of time (h) on the abscissa. * Ketoacid levels exceeded 8 mmol/l in this patient, the true value was beyond the range of measurement