Introduction: Metformin’s overall safety, proven efficacy, and relatively low cost make it a staple in the treatment of type 2 diabetes. However, metformin-associated lactic acidosis (MALA) remains a rare but life-threatening complication. The incidence of MALA is 10 per 100,000 patients, yet mortality remains high, approaching 30–50% in critically ill patients. Early recognition and prompt initiation of renal replacement therapy are critical to improving outcomes in severe cases.
Case Description: A 73-year-old man with type 2 diabetes mellitus treated with metformin presented after being found unresponsive. On arrival, he was profoundly hypotensive and bradycardic, requiring atropine, vasopressor support, and endotracheal intubation. Initial evaluation revealed severe hyperkalemia of 8.8 mEq/L (normal 3.5-5 mEq/L) with widened QRS complexes and peaked T waves on electrocardiogram, creatinine 6.89 mg/dl (baseline creatinine 1.10 -1.20 mg/dl), and profound lactic acidosis with severe acidemia (pH < 6.85 [normal 7.35-7.45], lactate 18 mmol/L [normal < 2.5 mmol/l]). He was admitted to the intensive care unit and required renal replacement therapy. Lactic acidosis was suspected to be multifactorial, with metformin toxicity considered a major contributor, supported by a markedly elevated serum metformin level of 35 µg/mL (normal < 0.10 mcg/mL) in the setting of shock and renal failure. His hospital course was complicated by mixed shock and diabetic ketoacidosis, which was resolved with antibiotics and insulin. With correction of metabolic abnormalities, his hemodynamic status and mental status improved, and he was successfully extubated. The patient was ultimately stabilized and discharged to a skilled nursing facility.
Discussion: MALA typically occurs in the setting of metformin accumulation due to impaired renal clearance and is precipitated by acute conditions such as shock, hypoxia, or sepsis that exacerbate lactate overproduction and impaired hepatic metabolism. Metformin is eliminated renally, with a half-life of 3–5 hours that may extend to 13 hours in chronic kidney disease (CKD). Therapeutic plasma concentrations are typically 0.5–4 mcg/mL, with levels reaching >5 mcg/mL in those with MALA and >15–20 mcg/mL in severe cases requiring renal replacement therapy. The patient in this case had a normal baseline creatinine yet developed MALA, which highlights the importance of keeping MALA on the differential even in patients with a normal baseline creatinine, as AKI can develop for a variety of reasons, in turn leading to metformin accumulation and MALA. MALA should be strongly suspected in patients on metformin who present with shock and high anion gap metabolic acidosis, particularly when renal failure is present, and prompt initiation of renal replacement therapy can be lifesaving even in cases with markedly elevated metformin levels.
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