Metformin improves survival in intensive care unit patients, but why?

We read with interest the study by Christiansen and colleagues [1] in the previous issue of Critical Care. In a large cohort study, the authors report that among diabetic patients who are admitted to the ICU, the preadmission use of metformin is associated with a lower mortality rate. Here, we highlight that metformin limits ischemiareperfusion injury (IRI) and modulates inflammation by increased adenosine receptor stimulation and propose that these mechanisms contribute to the reported survival benefit. In prospective studies in patients with diabetes, metformin use is associated with lower cardiovascular mortality compared with alternative glucose-lowering agents, suggesting a direct cardioprotective effect of metformin [2]. In animal studies, metformin potently limits myocardial infarct size [2]. This is caused, at least in part, by increased formation of the endogenous nucleoside adenosine [3]. Adenosine receptor stimulation increases