Intensive Insulin Therapy in Hospitalized Patients: A Systematic Review

Background: The benefits and harms of intensive insulin therapy (IIT) titrated to strict glycemic targets in hospitalized patients remain uncertain. Purpose: To evaluate the benefits and harms of IIT in hospitalized patients. Data Sources: MEDLINE and Cochrane Database of Systematic Reviews from 1950 to January 2010, reference lists, experts, and unpublished sources. Study Selection: English-language randomized, controlled trials comparing protocols titrated to strict or less strict glycemic targets. Data Extraction: Two reviewers independently abstracted data from each study on sample, setting, glycemic control interventions, glycemic targets, mean glucose levels achieved, and outcomes. Results were grouped by patient population or setting. A random-effects model was used to combine trial data on short-term mortality (<= 28 days), long-term mortality (90 or 180 days), infection, length of stay, and hypoglycemia. The Grading of Recommendations Assessment, Development, and Evaluation system was used to rate the overall body of evidence for each outcome. Data Synthesis: In a meta-analysis of 21 trials in intensive care unit, perioperative care, myocardial infarction, and stroke or brain injury settings, IIT did not affect short-term mortality (relative risk, 1.00 [95% CI, 0.94 to 1.07]). No consistent evidence showed that IIT reduced long-term mortality, infection rates, length of stay, or the need for renal replacement therapy. No evidence of benefit from IIT was reported in any hospital setting, although the best evidence for lack of benefit was in intensive care unit settings. Data combined from 10 trials showed that IIT was associated with a high risk for severe hypoglycemia (relative risk, 6.00 [CI, 4.06 to 8.87]; P < 0.001). Risk for IIT-associated hypoglycemia was increased in all hospital settings. Limitations: Methodological shortcomings and inconsistencies limit the data in perioperative care, myocardial infarction, and stroke or brain injury settings. Differences in insulin protocols and patient and hospital characteristics may affect generalizability across treatment settings. Conclusion: No consistent evidence demonstrates that IIT targeted to strict glycemic control compared with less strict glycemic control improves health outcomes in hospitalized patients. Furthermore, IIT is associated with an increased risk for severe hypoglycemia.