SUN-652 - Fulminant Metformin-Associated Lactic Acidosis Triggered by Acute Illness

Introduction
Metformin is the first-line therapy for type 2 diabetes mellitus due to its glycemic efficacy and cardiovascular benefit. Metformin-associated lactic acidosis (MALA) is rare but potentially fatal, with reported 30-day mortality of 14.8%–36.2%. Although metformin is considered safe at eGFR ≥30 mL/min/1.73 m² under stable conditions, most MALA episodes occur during acute illness, when renal hypoperfusion and acute kidney injury (AKI) impair drug clearance rather than advanced chronic kidney disease alone. Large cohort studies show no increased acidosis risk in stable patients with eGFR >30 mL/min/1.73 m², whereas AKI markedly increases risk. ADA/KDIGO guidelines recommend holding metformin during acute illness. This case highlights a preventable catastrophic outcome and gaps in sick-day management.

Case Presentation
A 77-year-old man with type 2 diabetes mellitus, hypertension, and hyperlipidemia presented with 24 hours of profuse bilious vomiting and diarrhea while continuing metformin 1000 mg twice daily. Baseline renal function was normal (creatinine 1.16 mg/dL; eGFR >60 mL/min/1.73 m²). On arrival, he was obtunded and tachypneic in metabolic shock requiring intubation. Laboratory testing revealed severe high–anion gap metabolic acidosis (pH 6.80, bicarbonate 3.4 mmol/L, anion gap 56.6 mmol/L), extreme hyperlactatemia (22.7 mmol/L), and severe AKI (creatinine 11.4 mg/dL). Amylase (1063 U/L) and lipase (231 U/L; >3× ULN) were elevated. Computed tomography demonstrated peripancreatic inflammation without gallstones, obstruction, or necrosis. Infectious, ischemic, and alternative toxic etiologies were excluded.

Fulminant MALA with concurrent acute pancreatitis of uncertain etiology was diagnosed. Severe acidemia (pH < 7.1) and hyperlactatemia (≥20 mmol/L) met criteria for urgent renal replacement therapy. Intermittent hemodialysis was initiated within 6 hours. After five sessions, lactate and arterial pH normalized by hospital day 3. The patient was extubated on day 5 and discharged dialysis-independent on day 12 with creatinine 1.5 mg/dL (eGFR 48 mL/min/1.73 m²).

Discussion
Metformin toxicity results from mitochondrial complex I inhibition, impairing oxidative phosphorylation and promoting lactate accumulation, amplified by AKI. Lactate ≥20 mmol/L with profound acidemia provides high diagnostic specificity for MALA when alternative causes are excluded. Although metformin may exacerbate pancreatic injury, ischemic injury from shock and acidemia was most likely. Early dialysis is associated with reduced mortality.

Conclusion
Acute illness–associated AKI can precipitate catastrophic MALA even in patients with previously normal renal function. Early recognition and prompt dialysis were lifesaving. This case reinforces sick-day education and proactive medication management as essential to safe metformin prescribing.

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