Clinical differences between metformin-associated lactic acidosis and metformin-unrelated lactic acidosis: A...

The extent to which metformin contributes to lactic acidosis in metformin-treated patients presenting to the emergency department (ED) remains unclear, particularly when blood metformin concentrations are unavailable. This study aimed to clarify the clinical differences between metformin-associated lactic acidosis (MALA) and metformin-unrelated lactic acidosis (MULA) on ED admission.

We conducted a retrospective study at a tertiary care hospital from January 1, 2023 to July 31, 2025. We included adult patients receiving metformin who presented to the ED with lactic acidosis, defined as pH < 7.35 and lactate ≥5 mmol/L. Patients were classified as having MALA if their serum metformin concentration at ED admission was ≥5 mg/L; others were categorized as MULA.

Among 14 patients with available serum metformin concentrations, 3 were classified as MALA and 11 as MULA. MALA patients presented with lower blood pressure at ED admission (median 65/36 versus 130/74 mmHg), more profound acidemia (median pH 7.03 [IQR 6.89-7.06] versus 7.22 [IQR 7.20-7.32]), and higher lactate levels (median 14.8 mmol/L [IQR 14.3-19.0] versus 7.3 mmol/L [IQR 5.7-12.5]). Serum creatinine was also higher in the MALA group (median 2.65 mg/dL [IQR 2.26-6.35]) than in the MULA group (median 1.16 mg/dL [IQR 0.97-1.39]).

Although the sample size was small, three clinical clues for identifying MALA may include severe acidemia with hyperlactatemia, kidney impairment, and hypotension. Clinicians may consider MALA when these findings coexist in the absence of measured blood metformin concentrations. Further large-scale studies are warranted to confirm our findings.