Safety and Feasibility of Metformin for Sepsis Induced AKI

Acute kidney injury (AKI) is an independent risk factor for death that affects 10-15% of hospitalized patients and more than 50% of patients admitted to the intensive care unit. Sepsis is the most frequent cause of AKI, affecting 48 million people worldwide every year, and accounting for approximately 11 million of annual global deaths. Despite these figures, there are no known therapies to prevent or reverse septic AKI; hence this study aims to establish the safety and feasibility of the implementation of metformin in the treatment of AKI in patients with sepsis. This study is the first critical step to inform the design of a future, full-scale efficacy randomized clinical trial.

Inclusion Criteria: 1. Age \> 18 years 2. Admitted to the ICU with sepsis per sepsis 3 criteria (defined as suspected infection or initiation of anti-biotics plus an increase in SOFA ≥ 2 points) 3. Available enteral access Exclusion Criteria: 1. Estimated glomerular filtration rate (eGFR) \< 30 ml/min/1.73m2 prior to study drug administration 2. Not expected to survive more than 24 hours 3. Advanced directive to withhold life-sustaining treatment 4. Metformin use in the last 30 days from admission (assessed by medical or refill prescription history, and by medication reconciliation) 5. The treating clinician believes that participation in the trial would not be in the best interests of the patient 6. Known or suspected pregnancy 7. On mechanical circulatory support of any kind 8. History of allergy to metformin 9. Having severe metabolic acidosis defined by a venous or arterial pH \< 7.2, with PaCO2 \< 45 or PvCO2 \< 50 mmHg at the time of enrolment. * Patients co-enrolled in observational studies will be eligible for enrollment in LiMiT AKI. However, patients enrolled in interventional studies will need to be assessed on an individual basis to define whether the patient will be eligible. * Children will be excluded from recruitment for this study. Etiologic causes of sepsis, acute kidney injury, and prognostic factors for children differ from those for adults; and for these reasons the proposed study focuses only on the adult population (age 18 years or older).