Hyperglycemia in the intensive care unit: is insulin the only option?

Current guidelines advocate the use of insulin for the management of hyperglycemia in the hospital setting. However, insulin is limited by a narrow therapeutic window, frequent errors, a need for expertise and systems-based monitoring, and lack of specificity for metabolic abnormalities that occur during critical illness. As a result, non-insulin alternatives have garnered increasing interest for managing hyperglycemia in the hospital. However, non-insulin therapies have had safety and tolerability concerns, patients may still need insulin for glycemic control, and there have been limited outcomes data supporting their use. In the study by Christiansen and colleagues in the previous issue of Critical Care, pre-admission metformin therapy was associated with reduced mortality in critically ill patients with type 2 diabetes. The mortality benefit persisted after controlling for other variables, and was particularly prominent when metformin was continued during admission. Furthermore, the reduction in mortality was observed despite a slightly increased prevalence of lactic acidosis in metformin users. The protective effects of metformin are purported to be related to pleiotropic, possibly anti-inflammatory mechanisms, raising the question of benefit in patients without diabetes. Thus, the findings warrant a re-appraisal of the risks and benefits of metformin use during critical illness. However, in order to justify the revision of multiple guidelines and changes in product labeling, clinical trials in carefully selected patient populations are indicated.