A Patient-Level Meta-Analysis of Intensive Glucose Control in Critically Ill Adults

NEJM Evid. 2024 Aug;3(8):EVIDoa2400082. doi: 10.1056/EVIDoa2400082. Epub 2024 Jun 12.

Abstract

Background: Whether intensive glucose control reduces mortality in critically ill patients remains uncertain. Patient-level meta-analyses can provide more precise estimates of treatment effects than are currently available.

Methods: We pooled individual patient data from randomized trials investigating intensive glucose control in critically ill adults. The primary outcome was in-hospital mortality. Secondary outcomes included survival to 90 days and time to live cessation of treatment with vasopressors or inotropes, mechanical ventilation, and newly commenced renal replacement. Severe hypoglycemia was a safety outcome.

Results: Of 38 eligible trials (n=29,537 participants), 20 (n=14,171 participants) provided individual patient data including in-hospital mortality status for 7059 and 7049 participants allocated to intensive and conventional glucose control, respectively. Of these 1930 (27.3%) and 1891 (26.8%) individuals assigned to intensive and conventional control, respectively, died (risk ratio, 1.02; 95% confidence interval [CI], 0.96 to 1.07; P=0.52; moderate certainty). There was no apparent heterogeneity of treatment effect on in-hospital mortality in any examined subgroups. Intensive glucose control increased the risk of severe hypoglycemia (risk ratio, 3.38; 95% CI, 2.99 to 3.83; P<0.0001).

Conclusions: Intensive glucose control was not associated with reduced mortality risk but increased the risk of severe hypoglycemia. We did not identify a subgroup of patients in whom intensive glucose control was beneficial. (Funded by the Australian National Health and Medical Research Council and others; PROSPERO number CRD42021278869.).

Publication types

  • Meta-Analysis

MeSH terms

  • Adult
  • Blood Glucose / analysis
  • Blood Glucose / drug effects
  • Blood Glucose / metabolism
  • Critical Illness* / mortality
  • Glycemic Control / methods
  • Hospital Mortality*
  • Humans
  • Hyperglycemia / blood
  • Hyperglycemia / drug therapy
  • Hyperglycemia / mortality
  • Hypoglycemia* / chemically induced
  • Randomized Controlled Trials as Topic

Substances

  • Blood Glucose