Intensive versus Conventional Glucose Control in Critically Ill Patients
Open accessAbstract
BACKGROUND: The optimal target range for blood glucose in critically ill patients remains unclear. METHODS: Within 24 hours after admission to an intensive care unit (ICU), adults who were expected to require treatment in the ICU on 3 or more consecutive days were randomly assigned to undergo either intensive glucose control, with a target blood glucose range of 81 to 108 mg per deciliter (4.5 to 6.0 mmol per liter), or conventional glucose control, with a target of 180 mg or less per deciliter (10.0 mmol or less per liter). We defined the primary end point as death from any cause within 90 days after randomization. RESULTS: Of the 6104 patients who underwent randomization, 3054 were assigned to undergo intensive control and 3050 to undergo conventional control; data with regard to the primary outcome at day 90 were available for 3010 and 3012 patients, respectively. The two groups had similar characteristics at baseline. A total of 829 patients (27.5%) in the intensive-control group and 751 (24.9%) in the conventional-control group died (odds ratio for intensive control, 1.14; 95% confidence interval, 1.02 to 1.28; P=0.02). The treatment effect did not differ significantly between operative (surgical) patients and nonoperative (medical) patients (odds ratio for death in the intensive-control group, 1.31 and 1.07, respectively; P=0.10). Severe hypoglycemia (blood glucose level, < or = 40 mg per deciliter [2.2 mmol per liter]) was reported in 206 of 3016 patients (6.8%) in the intensive-control group and 15 of 3014 (0.5%) in the conventional-control group (P<0.001). There was no significant difference between the two treatment groups in the median number of days in the ICU (P=0.84) or hospital (P=0.86) or the median number of days of mechanical ventilation (P=0.56) or renal-replacement therapy (P=0.39). CONCLUSIONS: In this large, international, randomized trial, we found that intensive glucose control increased mortality among adults in the ICU: a blood glucose target of 180 mg or less per deciliter resulted in lower mortality than did a target of 81 to 108 mg per deciliter. (ClinicalTrials.gov number, NCT00220987.)
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Inpatient hyperglycemia is associated with more complications, including surgical site infections, mortality, and longer hospital stays.
“Inpatient hyperglycemia is associated with increased complications including surgical site infections, mortality, and increased length of hospital stay.91–93”
From American Association of Clinical Endocrinology Clinical Practice Guideline: Developing a Diabetes Mellitus Comprehensive Care Plan-2022 Update. (2022) · cites this paper as [93]
The paper’s opening background passage (p. 1284, included under Results in our copy) says hyperglycemia, particularly severe hyperglycemia, is associated with increased morbidity and mortality. It does not identify surgical-site infections or longer hospital stays as associated outcomes. Its Results compare hospital-stay duration between glucose-control groups, not by presence of hyperglycemia. (LLM, conf=0.87)
Experimental — accuracy not yet measuredTwo randomised controlled trials conducted in critically ill patients in the intensive care unit setting identified severe hypoglycaemia as an independent risk factor for mortality.
“Two randomised controlled trials conducted in critically ill patients in the intensive care unit setting also identified severe hypoglycaemia as an independent risk factor for mortality.25 26”
From The association between symptomatic, severe hypoglycaemia and mortality in type 2 diabetes: Retrospective epidemiological analysis of the ACCORD study (2010) · cites this paper as [26]
The Results and Discussion describe a randomized ICU trial in which intensive glucose control increased both 90-day mortality and severe hypoglycemia. They do not identify severe hypoglycemia itself as an independent risk factor for mortality; the adjusted mortality finding concerns treatment assignment, not hypoglycemia. (LLM, conf=0.88)
Experimental — accuracy not yet measuredAggressive lowering of glycemia in the ICU may be associated with increased mortality.
“However, subsequent studies showed that such aggressive lowering of glycemia in the ICU is not uniformly beneficial, markedly increases the risk of severe hypoglycemia, and may be associated with increased mortality (70–74).”
From Hypoglycemia and Diabetes: A Report of a Workgroup of the American Diabetes Association and The Endocrine Society (2013) · cites this paper as [71]
Experimental — accuracy not yet measuredAggressive lowering of glycemia in the ICU markedly increases the risk of severe hypoglycemia.
“However, subsequent studies showed that such aggressive lowering of glycemia in the ICU is not uniformly beneficial, markedly increases the risk of severe hypoglycemia, and may be associated with increased mortality (70–74).”
From Hypoglycemia and Diabetes: A Report of a Workgroup of the American Diabetes Association and The Endocrine Society (2013) · cites this paper as [71]
Aggressive lowering of glycemia in the ICU is not uniformly beneficial.
“However, subsequent studies showed that such aggressive lowering of glycemia in the ICU is not uniformly beneficial, markedly increases the risk of severe hypoglycemia, and may be associated with increased mortality (70–74).”
From Hypoglycemia and Diabetes: A Report of a Workgroup of the American Diabetes Association and The Endocrine Society (2013) · cites this paper as [71]
Experimental — accuracy not yet measured
Several multicenter studies, including the NICE-SUGAR trial, in critically ill hospitalized individuals in medical and surgical ICUs failed to replicate the Van den Berghe data.
“However, several multicenter studies, including the Normoglycemia in Intensive Care Evaluation and Survival Using Glucose Algorithm Regulation (NICE-SUGAR) trial, in critically ill hospitalized individuals in medical and surgical ICUs (29-31) failed to replicate these data.”
From 16. Diabetes Care in the Hospital: Standards of Care in Diabetes—2026 (2026) · cites this paper as [31]
The overall rate of severe hypoglycemic events in international trials ranged from 5% to 28.6%.
“The overall rate of severe hypoglycemic events in international trials ranged between 5% to 28.6%.3,4,7,8,18,19”
From A comparison study of continuous insulin infusion protocols in the medical intensive care unit: Computer-guided vs. Standard column-based algorithms (2010) · cites this paper as [7]
The NICE-SUGAR multicenter study found an absolute increase in mortality with intensive glucose control.
“the large multicenter normoglycaemia in intensive care evaluation and survival using glucose algorithm regulation (NICE-SUGAR) study reported an absolute increase in mortality rate with intensive glucose control.7”
From A comparison study of continuous insulin infusion protocols in the medical intensive care unit: Computer-guided vs. Standard column-based algorithms (2010) · cites this paper as [7]
Intensified insulin therapy in critically ill patients is associated with more severe hypoglycemic events than less aggressive glycemic control protocols.
“In addition, intensified insulin therapy in critically-ill patients has been shown to be associated with a higher rate of severe hypoglycemic events than less aggressive glycemic control protocols.7–10”
From A comparison study of continuous insulin infusion protocols in the medical intensive care unit: Computer-guided vs. Standard column-based algorithms (2010) · cites this paper as [7]
Aggressive lowering of glycemia in the ICU is not uniformly beneficial.
“However, subsequent studies showed that such aggressive lowering of glycemia in the ICU is not uniformly bene fi cial, markedly increases the risk of severe hypoglycemia, and may be associated with increased mortality (70 -74).”
From Hypoglycemia and Diabetes: A Report of a Workgroup of the American Diabetes Association and The Endocrine Society (2013) · cites this paper as [71]
Aggressive lowering of glycemia in the ICU may be associated with increased mortality.
“However, subsequent studies showed that such aggressive lowering of glycemia in the ICU is not uniformly bene fi cial, markedly increases the risk of severe hypoglycemia, and may be associated with increased mortality (70 -74).”
From Hypoglycemia and Diabetes: A Report of a Workgroup of the American Diabetes Association and The Endocrine Society (2013) · cites this paper as [71]
Aggressive lowering of glycemia in the ICU markedly increases the risk of severe hypoglycemia.
“However, subsequent studies showed that such aggressive lowering of glycemia in the ICU is not uniformly bene fi cial, markedly increases the risk of severe hypoglycemia, and may be associated with increased mortality (70 -74).”
From Hypoglycemia and Diabetes: A Report of a Workgroup of the American Diabetes Association and The Endocrine Society (2013) · cites this paper as [71]
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- Authors
- Nice-Sugar Study Investigators
- Affiliations
- Royal North Shore Hospital (AU)
- Corresponding author
- Nice-Sugar Study Investigators
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2009-03-26
- Volume
- 360
- Issue
- 13
- Pages
- 1283-1297
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- OpenAlex
- W2145053281
- Semantic Scholar
- bb374a68091c6abc42b06843b90c2d56496fbc92
- Cited by
- 5,119
- References
- 38
- Citations by year
- 2026: 159 · 2025: 168 · 2024: 202 · 2023: 171 · 2022: 191 · 2021: 236 · 2020: 214 · 2019: 212 · 2018: 240 · 2017: 256 · 2016: 278 · 2015: 317 · 2014: 377 · 2013: 366 · 2012: 482
- FWCI
- 416.44
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- UWA Profiles and Research Repository (UWA) (submittedVersion)
- Research Online (University of Wollongong) (submittedVersion)
- Figshare (submittedVersion, cc-by)
- ANU Open Research (Australian National University) (submittedVersion)
- Funders
- University of Alberta
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hyperglycemia and glycemic control in critically ill and hospitalized patients
- Health Sciences › Medicine › Critical Care and Intensive Care Medicine › Intensive Care Unit Cognitive Disorders
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Keywords
- tight glycemic control, blood glucose target range, critically ill patients, intensive care unit, mortality, severe hypoglycemia, critically ill adults, mechanical ventilation, renal replacement therapy, ICU length of stay, length of hospital stay, intensive insulin therapy, glycemic control
- MeSH terms
- Adrenal Cortex Hormones, Blood Glucose, Critical Care, Female, Humans, Hyperglycemia, Hypoglycemia, Hypoglycemic Agents, Insulin, Intensive Care Units, Length of Stay, Male, Middle Aged, Critical Illness, Kaplan-Meier Estimate
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