Table 1.

Summary of major randomized controlled trials investigating the use of intensive vs conventional insulin therapy in critically-ill patients

Trial	Study population	Number of patients enrolled	Target blood glucose in the intensive insulin therapy group (mg/dL)	Target blood glucose in the conventional insulin therapy group (mg/dL)	Key mortality findings	Key morbidity findings
First Leuven Trial, 2001[1]	Single-center; surgical ICU	1548	80-110	180-200	Reduced ICU and in-hospital mortality in the intensive insulin therapy group	Reduced incidence of bloodstream infection, acute renal failure, red cell transfusion, and critical-illness neuropathy in the intensive insulin therapy group. Increased occurrence of severe hypoglycemia in the intensive insulin therapy group
Second Leuven Trial, 2006[24]	Single-center; medical ICU	1200	80-110	180-200	No mortality difference	Reduced incidence of newly acquired kidney injury, reduced duration of mechanical ventilation, and reduced lengths of ICU and hospital stays in the intensive insulin therapy group. Increased occurrence of hypoglycemia in the intensive insulin therapy group
Arabi et al[25], 2008	Single-center; mixed ICU, including medical, surgical, and trauma patients	523	80-110	180-200	No mortality difference	Increased occurrence of hypoglycemia in the intensive insulin therapy group
Brunkhorst et al[26], 2008	Multicenter; mixed ICUs; all patients with severe sepsis or septic shock	537	80-110	180-200	No mortality difference	No difference in the mean score for organ failure. Increased occurrence of severe hypoglycemia in the intensive insulin therapy group
De La Rosa Gdel et al[27], 2008	Single center; mixed ICU, including medical, surgical, and trauma patients	504	80-110	180-200	No mortality difference	Increased occurrence of severe hypoglycemia in the intensive insulin therapy group
Preiser et al[28], 2009	Multicenter; medical and surgical ICU patients	1078	79-110	140-180	No mortality difference	Increased occurrence of severe hypoglycemia in the intensive insulin therapy group
NICE-SUGAR Trial, 2009[2]	Multicenter; medical and surgical ICU patients	6104	81-108	144-180	Increased 90-d mortality in the intensive insulin therapy group	Similar between-group markers of morbidity, with the exception of an increased occurrence of severe hypoglycemia in the intensive insulin therapy group
Annane et al[29], 2010	Multicenter; all patients with septic shock	509	80-110	180-200	No mortality difference	Increased occurrence of severe hypoglycemia in the intensive insulin therapy group
Coester et al[30], 2010	Single center; all patients with severe traumatic brain injury	88	80-110	< 180	No mortality difference	No difference in neurologic outcomes. Increased occurrence of hypoglycemia in the intensive insulin therapy group
Green et al[31], 2010	Single center; mechanically-ventilated neurologic patients	81	80-110	≤ 150	No mortality difference	No difference in neurologic function at 90 d. Increased occurrence of hypoglycemia and severe hypoglycemia in the intensive insulin therapy group
Macrae et al[32], 2014	Multicenter; medical and surgical pediatric patients	1369	72-126	180-216	No mortality difference	No difference in ventilator-free survival. Increased occurrence of severe hypoglycemia in the intensive insulin therapy group

ICU: Intensive care unit.