Metformin Use and Metformin-associated Lactic Acidosis in Intensive Care Unit Patients with Diabetes

Abstract

Metformin is a very potent anti-diabetic drug that has become the drug of choice for the treatment of type 2 diabetes. In addition to its glucose-lowering properties, it also reduces all-cause mortality through its anti-inflammatory and cardioprotective effects. Although metformin-associated lactic acidosis (MALA) is a very rare event, the mortality associated with it is close to 50%. As it is excreted through the kidney, MALA is frequently seen in patients on metformin with risk factors for developing acute kidney injury. Metformin increases the plasma lactate level in a concentration-dependent manner by inhibiting mitochondrial respiration, usually in the presence of a secondary event that disrupts lactate production or clearance. The incidence of acute kidney injury is very high in critically ill patients contributed by circulatory defects as well as contrast-induced nephropathy, the incidence of which is also high in this subset of the population. Because of this potential risk, metformin is frequently discontinued in diabetic patients admitted to the intensive care unit. Blood glucose variability and hypoglycemia, however, are both related to poor intensive care unit (ICU) outcomes and in order to prevent this in diabetic patients admitted to ICU, oral hypoglycemic agents are frequently switched to intravenous or subcutaneous insulin regimens, which allows for closer monitoring and better blood glucose control.