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Cited by 25Hyperglycemia and glycemic control in critically ill and hospitalized patientsDiabetes Management and ResearchIntensive Care Unit Cognitive Disorders

A patient-level meta-analysis of intensive glucose control in critically ill adults

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Adigbli, Derick, Li, Yang, Hammond, Naomi, Chatoor, Richard, Devaux, Anthony G., Li, Qiang, Billot, Laurent, Annane, Djillali +29 more·2024·NEJM Evidence
DOI 10.1056/evidoa2400082
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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.).

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  • The findings from the NICE-SUGAR trial, supported by several meta-analyses, showed higher rates of hypoglycemia and an increase in mortality with more aggressive glycemic management goals compared with moderate glycemic goals.

    “The findings from the NICE-SUGAR trial, supported by several meta-analyses showed higher rates of hypoglycemia and an increase in mortality with more aggressive glycemic management goals compared with moderate glycemic goals (29,32,33).”

    From 16. Diabetes Care in the Hospital: Standards of Care in Diabetes—2026 (2026) · cites this paper as [33]

    The Introduction (page unavailable) reports that NICE-SUGAR found increased 90-day mortality with a normoglycemia target, and the Discussion says trials and meta-analyses found increased severe hypoglycemia with intensive control. But this paper's own pooled analysis found no significant increase in mortality (Abstract, page unavailable), so it does not support attributing an increased-mortality finding to the meta-analysis. (LLM, conf=0.88)

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Authors
Adigbli, D., Li, Y., Hammond, N., Chatoor, R., Devaux, A. G., Li, Q., Billot, L., Annane, D., Arabi, Y., Bilotta, F., Bohé, J., Brunkhorst, F. M., Cavalcanti, A. B., Cook, D., Engel, C., Green-LaRoche, D., He, W., Henderson, W., Hoedemaekers, C., Iapichino, G., Kalfon, P., de La Rosa, G., Lahooti, A., Mackenzie, I., Mahendran, S., Mélot, C., Mitchell, I., Oksanen, T., Polli, F., Preiser, J.-C., Garcia Soriano, F., Vlok, R., Wang, L., Xu, Y., Delaney, A. P., Di Tanna, G. L., & Finfer, S.
Affiliations
  • The University of Melbourne (AU)
  • The George Institute for Global Health (GB)
  • Royal North Shore Hospital (AU)
  • The George Institute for Global Health (AU)
  • Université Paris-Saclay (FR)
  • King Saud bin Abdulaziz University for Health Sciences (SA)
  • Sapienza University of Rome (IT)
  • Hospices Civils de Lyon (FR)
  • Jena University Hospital (DE)
  • HCor Research Institute, São Paulo, Brazil
  • McMaster University (CA)
  • Leipzig University (DE)
  • Department of Neurology, Tufts University School of Medicine, Boston
  • Beijing Tongren Hospital (CN)
  • University of British Columbia (CA)
  • Radboud University Medical Center (NL)
  • University of Milan (IT)
  • Hôpital de Beaumont (CH)
  • Hospital Pablo Tobon Uribe, Medellín, Colombia
  • InterSystems (United States) (US)
  • The University of Sydney (AU)
  • Université Libre de Bruxelles (BE)
  • Australian National University (AU)
  • Helsinki University Hospital (FI)
  • Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico (IT)
  • Departamento de Clínica Médica–Emergências Clínicas, Faculdade de Medicina da Universidade de São Paulo, São Paulo
  • Zhejiang Chinese Medical University (CN)
  • Beijing Tsinghua Chang Gung Hospital (CN)
  • Department of Intensive Care, Austin Health, Melbourne, VIC, Australia
ORCID
Venue
NEJM Evidence
Publisher
Massachusetts Medical Society
Published
2024-07-23
Volume
3
Issue
8
Pages
EVIDoa2400082-EVIDoa2400082
ISSN
2766-5526 (ISSN-L)
DOI
10.1056/evidoa2400082
OpenAlex
W4399572665
Cited by
25
References
10
Citations by year
2026: 9 · 2025: 12 · 2024: 4
FWCI
1.47
Type
journal article
Language
en
Open access
Locations
  • NEJM Evidence (publishedVersion)
  • PubMed (publishedVersion)
  • UCL Discovery (University College London) (submittedVersion)
  • HAL (submittedVersion)
  • Cineca Institutional Research Information System (Tor Vergata University) (submittedVersion)
  • Bern Open Repository and Information System (University of Bern) (submittedVersion)
  • IRIS Research product catalog (Sapienza University of Rome) (submittedVersion)
  • Radboud Repository (Radboud University) (submittedVersion)
Funders
  • Agence Nationale de la Recherche (ANR-18-RHUS-0004)
  • Canadian Institutes of Health Research
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hyperglycemia and glycemic control in critically ill and hospitalized patients
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
  • Health Sciences › Medicine › Critical Care and Intensive Care Medicine › Intensive Care Unit Cognitive Disorders
Keywords
tight glycemic control, critically ill adults, in-hospital mortality, severe hypoglycemia, individual patient data, mechanical ventilation, renal replacement therapy, subgroup heterogeneity
MeSH terms
Glycemic Control, Adult, Blood Glucose, Humans, Hyperglycemia, Hypoglycemia, Randomized Controlled Trials as Topic, Critical Illness, Hospital Mortality

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