Normoglycemia in Intensive Care Evaluation–Survival Using Glucose Algorithm Regulation - NICE-SUGAR


The goal of the trial was to evaluate a strategy of intensive glucose control compared with conventional control in critically ill patients.


Intensive glucose control would be more effective in reducing mortality.

Study Design

  • Randomized
  • Parallel

Patients Enrolled: 6,104
Mean Follow Up: 90 days
Mean Patient Age: 60 years
Female: 37%

Patient Populations:

  • Patients admitted to the ICU and expected to be there for at least 3 days
  • Patients have or are expected to have an arterial catheter for blood draws in place


  • Age <18
  • Imminent death
  • Diabetic ketoacidosis or hyperosmolar state
  • Patients who are expected to be eating on the day following admission
  • Patients who previously suffered from hypoglycemia without full neurological recovery or patients who have a high risk for hypoglycemia
  • Inability to provide informed consent
  • Patient has already been in the ICU for 24 hours prior to consideration of enrollment in the study

Primary Endpoints:

  • All-cause mortality at 90 days

Secondary Endpoints:

  • Survival time
  • Cause-specific death
  • Duration of mechanical ventilation
  • Duration of renal-replacement therapy
  • Duration in the ICU
  • Duration in the hospital
  • All-cause mortality at 28 days
  • Place of death
  • Incidence of new organ failure
  • Positive blood culture
  • Blood transfusion

Drug/Procedures Used:

Patients admitted to the intensive care unit (ICU) were randomized to intensive glucose control (81-108 mg/dl; n = 3,054) versus conventional glucose control (<180 mg/dl; n = 3,050). In all patients, insulin was given intravenously and nutrition was given enterally.

Principal Findings:

Overall, 6,104 patients were randomized. There was no difference in baseline characteristics between the groups. The mean age was 60 years, 37% were women, body mass index was 28 kg/m2, 20% had diabetes, mechanical ventilation was used in 94%, renal-replacement therapy was used in 6%, sepsis was present in 22%, trauma was present in 14%, and APACHE II score ≥25 was present in 31%.

The incidence of the primary outcome, all-cause mortality at 90 days, occurred in 27.5% in the intensive group versus 24.9% of the conventional control group (p = 0.02). There was no difference in the primary outcome according to surgical or medical patients. Mortality at 28 days was 22.3% versus 20.8% (p = 0.17), respectively. The cause of death was cardiovascular shock in 20.3% versus 18.6%, other cardiovascular cause in 21.4% versus 17.2%, neurologic in 21.7% versus 25.8%, respiratory in 23.0% versus 23.6%, and other in 13.6% versus 14.8%, respectively for intensive versus conventional control.

Severe hypoglycemia occurred in 6.8% versus 0.5% (p


Among patients admitted to the ICU, intensive glucose control was not beneficial and in fact increased mortality at 90 days. This strategy increased mortality by an absolute 2.6%, which corresponded to a number needed to harm of only 38 patients. Severe hypoglycemia was more common in the intensive control group.

Previous studies have shown mixed results comparing these treatment strategies; however, the present trial had high statistical power with one of the longest follow-up periods. Only one-fifth of the study participants had a previous diagnosis of diabetes. It is unknown if low glucose levels, administration of insulin, or periodic severe hypoglycemia accounted for the harm with intensive glucose control. Unless a future study definitively disputes these findings or finds a subgroup of patients who benefits, the use of intensive glucose control in ICU patients should likely be discouraged.


The NICE-SUGAR Study Investigators. Intensive versus conventional glucose control in critically ill patients. N Engl J Med 2009;360:1283-97.

Keywords: Insulin, Intensive Care Units, Follow-Up Studies, Sepsis, Respiration, Artificial, Critical Care, Dissent and Disputes, Hypoglycemia, Glucose, Cause of Death, Body Mass Index, APACHE, Critical Illness, Diabetes Mellitus

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