Rare Fulminant MALA in a Renally Intact Host: A Deadly Metabolic Mismatch

Introduction: Metformin-associated lactic acidosis (MALA) is rare, noted in less than 10 cases per 100,000 patients, with mortality exceeding 30%. We present a case of severe MALA in patient without prior chronic kidney disease, emphasizing the role of early renal replacement therapy (RRT) in reversing profound metabolic and hemodynamic derangements.


Description: A 56-year-old man with type 2 diabetes mellitus (on metformin, insulin, and an SGLT2 inhibitor) and hypertension presented with acute encephalopathy and hemodynamic instability. He progressed to a shock state requiring vasopressor support and mechanical ventilation. Laboratory findings were concerning for severe acidemia (pH < 6.8, HCO₃⁻ < 4 mEq/L), lactic acid of 21 mmol/L, potassium >8.0 mEq/L, and creatinine 8.6 mg/dL (baseline 0.6). After gathering history from family, no intentional overdose was noted. A formal diagnosis of MALA was made, and the patient was started on emergent RRT for metformin and lactic acid clearance. Over the course of a few days, the initial laboratory metformin level resulted at 58 mcg/mL (normal < 2 mcg/mL), confirming our diagnosis. After treatment with renal replacement therapy, the patient significantly improved, regained mentation, and was eventually extubated. He was discharged home with no residual complications.


Discussion: Metformin inhibits mitochondrial respiration, reducing lactate clearance and predisposing to severe acidemia. Most reported cases of MALA involve identifiable risk factors, unlike our relatively healthy patient with preserved renal function. Risk factors for MALA include renal impairment leading to metformin accumulation, hepatic dysfunction impairing lactate metabolism, and tissue hypoxia leading to increased lactate production; none of which were present in our patient. Serum metformin levels are rarely available in acute care, making clinical suspicion and timely recognition critical. A pH < 7.0 and lactate >15 mmol/L are associated with poor prognosis but should not delay initiation of RRT, which remains life-saving. This case adds to growing evidence that preserved baseline renal function does not eliminate the risk of life-threatening MALA.