Life-Threatening Acidosis With Metformin and Dapagliflozin Combination Therapy: A Case Report.

Euglycemic keto-acidosis is a known complication of dapagliflozin. However, acidosis can be life-threatening when dapagliflozin is used as a combination therapy with metformin. Our patient was a 64-year-old male, with a history of well-controlled type 2 diabetes mellitus on metformin and dapagliflozin, admitted with vomiting and diarrhea for several days. On presentation, the patient was hypotensive and severely acidotic (pH < 6.7; bicarbonate <5 mmol/L) with an anion gap of 47. Other labs included elevated lactate (19.48 mmol/L), creatinine of 10.39 mg/dL, and elevated beta-hydroxybutyrate levels. The patient was intubated and started on dual vasopressors, insulin drip, and i.v. hydration. Due to worsening acidosis, bicarbonate drip and, subsequently, continuous dialysis was started. The patient's acidosis normalized after two days of dialysis, and he was extubated by day three and discharged by day seven. Dapagliflozin leads to keto-acidosis due to increased hepatic ketogenesis and adipose tissue lipolysis. It also promotes natriuresis, glycosuria, and free water loss. Recurrent vomiting and poor oral intake with concomitant lactic acidosis with metformin can lead to life-threatening acidosis. Clinicians should remain cognizant of the possibility of severe acidosis with the combination therapy of dapagliflozin and metformin in severe dehydration. Adequate hydration may prevent this life-threatening complication.