The NICE-SUGAR trial: Intensive glycemic control harmful in the ICU [Classics Series]

1. Intensive glycemic control in critically ill patients significantly increases 90-day mortality when compared to conventional glycemic control.

2. The incidence of severe hypoglycemia was significantly higher in patients receiving intensive glycemic control.

Original Date of Publication: March 26, 2009

This study summary is an excerpt from the book 2 Minute Medicine’s The Classics in Medicine: Summaries of the Landmark Trials, 2e (The Classics Series).

Study Rundown: In the intensive care unit (ICU), hyperglycemia is a common problem that is associated with increased morbidity and mortality. Previously conducted trials, systematic reviews, and meta-analyses had reached conflicting conclusions on the effects of intensive glycemic control. Different groups, however, recommended intensive control for critically ill patients. The Normoglycemia in Intensive Care Evaluation-Survival Using Glucose Algorithm Regulation (NICE-SUGAR) trial sought to determine the impacts of intensive glycemic control on mortality in ICU patients. In summary, the trial demonstrated that intensive glucose control to target 81-108 mg/dL (4.5-6.0 mmol/L) significantly increased 90-day mortality (OR 1.14; 95%CI 1.02-1.28; ARI 2.6%, NNH 38) when compared to conventional glucose control to target ≤180 mg/dL (10.0 mmol/L). Moreover, the risk of severe hypoglycemia was significantly higher in the intensive control group (OR 14.7; 95%CI 9.0-25.9). Based on the findings of this study, intensive glucose control was not recommended for patients in the ICU.

Click to read the study in NEJM

In-Depth [randomized, controlled study]: The study involved 6,104 participants recruited from 42 hospitals from across Australia, New Zealand, and Canada. Patients were eligible if they stayed a minimum of 3 consecutive days in the ICU. Participants were randomly assigned to either intensive glucose control (target blood glucose between 81-108 mg/dL, or 4.5-6.0 mmol/L) or conventional glucose control (target blood glucose ≤180 mg/dL, or ≤10 mmol/L). Glucose control was achieved through insulin infusion as needed. The intervention was stopped when the patient was eating or discharged from the ICU. The primary outcome was death from any cause within 90 days after randomization. Secondary outcomes included survival time in the first 90 days, cause-specific death, and durations of mechanical ventilation/renal replacement therapy/ICU stay/hospital stay.

Intensive glucose control significantly increased the risk of mortality at day 90 when compared to conventional control (OR 1.14; 95%CI 1.02-1.28; ARI 2.6%, NNH 38). The incidence of severe hypoglycemia was significantly higher in patients undergoing intensive glucose control (OR 14.7; 95%CI 9.0-25.9). There were no significant differences between the groups in mechanical ventilation (p=0.56) or renal replacement therapy requirements (p=0.39). Moreover, there were no differences between the groups in terms of duration of ICU (p=0.84) or hospital stay (p=0.86).

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