A 76–year-old white male, with type 2 diabetes mellitus (DM), presented with three days history of confusion and difficulty finding words which started after aggressive vomiting of two days duration. His medications list included metformin and glipizide. On examination, patient was alert, awake, but disoriented to place and time. Rest of the neurological and physical exam was unremarkable. Significant laboratory parameters showed glucose of 141 mg/dl, lactate level of 6 mmol/l, high anion gap metabolic acidosis without osmolality gap. Ethanol, acetaminophen, amino salicylic acid (ASA), white cells count with differential, and kidney function were within the normal limits. Urinalysis was negative for ketones. Two sets of blood cultures and a urine culture didn’t grow any organisms. Computed tomography (CT) and magnetic resonance imaging (MRI) with and without contrast of the head were unremarkable.
Patient didn’t show any signs of sepsis. Since his glucose level was not significantly elevated, the diagnosis of diabetic ketoacidosis (DKA) was ruled out. His symptoms with the high anion gap metabolic acidosis were thought to be secondary to metformin associated lactic acidosis (MALA) after common possibilities were excluded as an etiology. Patient was treated with supportive care and his symptoms resolved in two days after stopping the metformin, in correlation with lactate normalization.
Metformin associated lactic acidosis (MALA) is extremely rare with incidence in patients on metformin ranging from 9 to 47 per 100.000 patient-year. However, mortality rate is about 30%. Hypoglycemia could happen with metformin toxicity. However, this is not the rule since metformin works mostly on inhibition of the endogenous overproduction of glucose, with only slight effect on peripheral consumption. Symptoms of lactic acidosis are nonspecific and may include anorexia, nausea, vomiting, abdominal pain, lethargy, hyperventilation, and hypotension.
MALA is a diagnosis of exclusion in the presence of arterial pH < 7.35 and plasma lactate concentrations > 5.0 mmol/l. It is highly suspected in a patient with unidentified etiology of lactic acidosis in the presence of risk factors. Most cases have occurred in patients with conditions that predispose to hypoperfusion and hypoxemia such as acute or progressive renal impairment, acute or progressive heart failure, acute pulmonary decompensation, and sepsis; however, none were found in our patient. Although it could be a serious condition resulting in high mortality and morbidity rates, conservative treatment is usually sufficient to treat most cases of MALA, especially mild ones.
Despite its rarity, lactic acidosis related to metformin remains a concern because of serious complications and high mortality rate. In any high anion gap metabolic acidosis with unknown etiology, it is very important to review all medications carefully to address potential culprit medications.
To cite this abstract:Haddad T, Kabach A, Ayan M, Alkhreisat M, Abuzaid A, Hazeem M. Presumed Metformin Associated Lactic Acidosis with Normal Kidney Function. Abstract published at Hospital Medicine 2015, March 29-April 1, National Harbor, Md. Abstract 443. Journal of Hospital Medicine. 2015; 10 (suppl 2). https://www.shmabstracts.com/abstract/presumed-metformin-associated-lactic-acidosis-with-normal-kidney-function/. Accessed March 28, 2020.