The NICE-SUGAR trial found that intensive glycemic control (target blood sugar 81-108 mg/dL) using intravenous insulin increased mortality compared to conventional glycemic control (target blood sugar ≤180 mg/dL) in critically ill ICU patients. The trial randomized over 6,000 patients across 42 centers to either intensive or conventional control groups. The primary outcome of 90-day mortality was higher in the intensive group. Therefore, the study concluded that a target blood sugar of less than 180 mg/dL resulted in lower mortality than a more intensive target of 81-108 mg/dL for critically ill ICU patients.

1. NICE-SUGAR
OVMC LANDMARK TRIALS SERIES

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

3. BACKGROUND
 Hyperglycemia is common in acutely ill patients
 Hyperglycemia is associated with increased
morbidity and mortality
 Prior to the NICE-SUGAR trial, a study in post-
surgical patients found decreased mortality with
sugar levels between 80-110, but this was a single
center study that could be prone to biases (eg
Hawthorne effect)

4. CLINICAL QUESTION
 In critically ill patients, how does intensive
glycemic control compare to conventional
glycemic control in reducing mortality?

5. DESIGN
 Analysis: Intention-to-treat
 Trial Design: Multicenter, non-blinded, parallel group, randomized, controlled trial
 Setting: 42 centers
 N=6,104
 Intensive (n=3,054)
 Conventional (n=3,050)
 Primary outcome: 90-day mortality (from any cause)
 Secondary outcomes: > 90 days survival, cause-specific death, and duration on ventilation, RRT, and
ICU/hospital stays
 Tertiary outcomes: mortality within 28 days after randomization, place of death (ICU, hospital ward, or
other), incidence of new organ failure, positive blood culture, transfusion requirement

6. POPULATION
Inclusion Criteria
 Expected to require ICU treatment for ≥3
consecutive days
 Medical and surgical ICU patients
Exclusion Criteria
 Not identified in study

7. INTERVENTIONS
 Participants randomized to:
 Intensive glycemic control (goal 81-108 mg/dL)
 Conventional glycemic control (goal ≤180 mg/dL)
 Glycemic control occurred with IV insulin infusion
 Conventional glycemic control group (goal ≤180 mg/dL) was started on IV insulin infusion for glucose levels >180
and was discontinued for blood glucose <144, when the patient was eating, or was discharged from the ICU.

8. Kaplan–Meier Curves Showing
Cumulative Survival of Patients
Who Received Intensive Insulin
Treatment or Conventional
Treatment in the Intensive Care
Unit (ICU).
Patients discharged alive from the ICU
(Panel A) and from the hospital (Panel
B) were considered to have survived.
In both cases, the differences
between the treatment groups were
significant (survival in ICU, nominal
P=0.005 and adjusted P<0.04; in-
hospital survival, nominal P=0.01).
Reference: NEJM Intensive Insulin
Therapy (2001)

9. CRITICISMS/LIMITATIONS/FUNDING
 Inability to blind treating personnel
 The intensive insulin therapy arm had more participants that happen to receive corticosteroids. This created
variability in glucose levels
 Insulin was given by IV infusion
 Study was discontinued prematurely (due to request by patient/surrogate, transition to palliative care) or by
physicians due to adverse events
FUNDING
Australian National Health and Medical Research Council
New Zealand Health Research Council
Vancouver General Hospital Foundation
Canadian Intensive Care Foundation
Canadian Diabetes Association

10. BOTTOM LINE
 Intensive glycemic control (target 81-108
mg/dL) increased deaths compared to
conventional control (target≤180) in ICU
patients: therefore, it can be concluded that a
blood sugar of <180 resulted in lower
mortality than a target 81-108.
Glucose Goal:140-180

11. DISCUSSION QUESTIONS
 In the NICE-TRIAL, what is the optimal target for glucose therapy?
 Can this data be extrapolated to inpatient medicine wards (in non-critically ill patients)?

12. DISCUSSION QUESTIONS
 In the NICE-TRIAL, what is the optimal target for glucose therapy?
 ANSWER: <180
 Can this data be extrapolated to inpatient medicine wards (in non-critically ill patients)?
 ANSWER: It depends!
 In non-critically ill patients, goal MORNING glucose can be <140 ONLY IF this can be safely achieved

13. BOARD-LIKE QUESTION
75 yo F is evaluated in the hospital for hip fracture. She
has a history of DM2.
Patient takes Atorvastatin, Metformin BID, Insulin
Glargine 20 units qHS, Insulin Lispro 5 units qAC.
Her average blood glucose level in the morning is 120
mg/dL. It is Sunday night, and your hospital does not do
hip fracture repairs. Patient is scheduled to be transferred
to neighboring county hospital on Monday morning.
Laboratory is significant for HgA1c 7.9% and a plasma
glucose of 210 mg/dL.
ADAPTED from MKSAP 17
QUESTION
Which is the most appropriate preoperative diabetic
management for this patient?
A. Discontinue Lispro. Start NPH because it is shorter
acting than Lantus.
B. Stop insulin glargine and insulin lispro, start IV
insulin infusion
C. Discontinue Glargine/Lispro. Continue Metformin
and add sliding scale.
D. Administer insulin glargine, but hold insulin lispro

14. BOARD-LIKE QUESTION
Educational Objective:
Managing DM2 medications in the preoperative
setting
Key Point:
You should continue long-acting insulin while
withhold shorting acting insulin during fasting
prior to surgical intervention.
Oral hypoglycemic are usually held in the inpatient
setting
ANSWER
Which is the most appropriate preoperative
diabetic management for this patient?
A. Discontinue Lispro. Start NPH because it is
shorter acting than Lantus.
B. Stop insulin glargine and insulin lispro, start IV
insulin infusion
C. Discontinue Glargine/Lispro. Continue
Metformin and add sliding scale.
D. Administer insulin glargine, but hold insulin
lispro

15. REFERENCES
 "Intensive versus Conventional Glucose Control in Critically Ill Patients." New England Journal of
Medicine 360.13 (2009): 1283-297
 Brain, LLC Peripheral. "NICE-SUGAR." NICE-SUGAR - Wiki Journal Club. N.p., n.d.
 Cheung, MD Andrew. "The NICE-SUGAR trial: Intensive glycemic control harmful in the ICU [Classics
Series]." 2 Minute Medicine. N.p., 03 Oct. 2014