Meta-Analysis

. 2024 Aug;3(8):EVIDoa2400082.

doi: 10.1056/EVIDoa2400082. Epub 2024 Jun 12.

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

Derick Adigbli^{1

2

3

4}, Yang Li¹, Naomi Hammond^{1

5}, Richard Chatoor⁵, Anthony G Devaux⁶, Qiang Li⁶, Laurent Billot⁶, Djillali Annane^{7

8

9

10}, Yaseen Arabi¹¹, Federico Bilotta¹², Julien Bohé¹³, Frank Martin Brunkhorst¹⁴, Alexandre Biasi Cavalcanti¹⁵, Deborah Cook¹⁶, Christoph Engel¹⁷, Deborah Green-LaRoche¹⁸, Wei He¹⁹, William Henderson²⁰, Cornelia Hoedemaekers²¹, Gaetano Iapichino²², Pierre Kalfon²³, Gisela de La Rosa²⁴, Afsaneh Lahooti^{1

25}, Iain Mackenzie²⁶, Sajeev Mahendran^{6

27}, Christian Mélot²⁸, Imogen Mitchell^{29

30}, Tuomas Oksanen³¹, Federico Polli³², Jean-Charles Preiser³³, Francisco Garcia Soriano³⁴, Ruan Vlok^{1

35}, Lingcong Wang³⁶, Yuan Xu³⁷, Anthony P Delaney^{1

6

27}, Gian Luca Di Tanna^{4

38

39}, Simon Finfer^{1

40

41}

Affiliations

¹ Critical Care Division, The George Institute for Global Health, Sydney.
² Department of Critical Care, Melbourne Medical School, University of Melbourne, Melbourne, VIC, Australia.
³ Medical School, Faculty of Medical Sciences, University College London, London.
⁴ Department of Intensive Care, Austin Health, Melbourne, VIC, Australia.
⁵ Royal North Shore Hospital, Malcolm Fisher Department of Intensive Care, St Leonards, NSW, Australia.
⁶ The George Institute for Global Health, Biostatistics and Data Science Division, Barangaroo, NSW, Australia.
⁷ Department of Intensive Care, Hôpital Raymond-Poincare, Garches, France.
⁸ PROMETHEUS IHU, Université Paris-Saclay, Garches, France.
⁹ Laboratory of Infection & Inflammation, School of Medicine Simone Veil Santé, Université Paris-Saclay, Montigny Le Bretonneux, France.
¹⁰ FHU SEPSIS (Saclay and Paris Seine Nord Endeavour to PerSonalize Interventions for Sepsis), Garches, France.
¹¹ Intensive Care Medicine, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia.
¹² Department of Anesthesiology and Intensive Care Medicine, University of Rome La Sapienza, Rome.
¹³ Service d'Anesthésie-Réanimation-Médecine Intensive, Hospices Civils de Lyon, Groupement Hospitalier Sud, Lyon, France.
¹⁴ Department of Anaesthesiology and Intensive Care Medicine, Jena University Hospital, Jena, Germany.
¹⁵ HCor Research Institute, São Paulo, Brazil.
¹⁶ Departments of Medicine, Clinical Epidemiology & Biostatistics (Division of Critical Care), McMaster University, Hamilton, ON, Canada.
¹⁷ Institute for Medical Informatics, Statistics and Epidemiology, Leipzig University, Leipzig, Germany.
¹⁸ Department of Neurology, Tufts University School of Medicine, Boston.
¹⁹ Department of Critical Care Medicine, Beijing Tongren Hospital, Capital Medical University, Beijing.
²⁰ Faculty of Medicine, The University of British Columbia, Vancouver, BC, Canada.
²¹ Department of Intensive Care Medicine, Radboud University Medical Center, Nijmegen, The Netherlands.
²² Anestesiologia e Rianimazione, Università degli Studi di Milano, Milan.
²³ La Casamance Private Hospital, Aubagne, France.
²⁴ Hospital Pablo Tobon Uribe, Medellín, Colombia.
²⁵ School of Science, Western Sydney University, Campbelltown, NSW, Australia.
²⁶ InterSystems Corporation, Cambridge, MA.
²⁷ Faculty of Medicine and Health, Northern Clinical School, The University of Sydney, St Leonards, NSW, Australia.
²⁸ Faculté de Médecine, Université Libre de Bruxelles, Brussels.
²⁹ Office of Research and Education, Canberra Health Services Library, Canberra, ACT, Australia.
³⁰ School of Medicine and Psychology, Australian National University, Canberra, ACT, Australia.
³¹ Division of Intensive Care Medicine, Department of Anesthesiology and Intensive Care, HUS Helsinki University Hospital, Helsinki.
³² Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan.
³³ Erasme University Hospital, Université Libre de Bruxelles, Brussels.
³⁴ Departamento de Clínica Médica-Emergências Clínicas, Faculdade de Medicina da Universidade de São Paulo, São Paulo.
³⁵ CareFlight Australia, Wentworthville, NSW, Australia.
³⁶ Department ICU, The First Affiliated Hospital, Zhejiang Chinese Medical University, Hangzhou, China.
³⁷ Department of Critical Care Medicine, School of Clinical Medicine, Beijing Tsinghua Changgung Hospital, Tsinghua University, Beijing.
³⁸ Department of Business Economics, Health and Social Care, University of Applied Sciences and Arts of Southern Switzerland, Lugano, Switzerland.
³⁹ Department of Clinical Care, University of Bern, Bern, Switzerland.
⁴⁰ Faculty of Medicine and Health, University of New South Wales, Randwick, NSW, Australia.
⁴¹ School of Public Health, Imperial College London, London.

PMID: 38864749
DOI: 10.1056/EVIDoa2400082

Meta-Analysis

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

Derick Adigbli et al. NEJM Evid. 2024 Aug.

. 2024 Aug;3(8):EVIDoa2400082.

doi: 10.1056/EVIDoa2400082. Epub 2024 Jun 12.

Authors

Affiliations

¹ Critical Care Division, The George Institute for Global Health, Sydney.
² Department of Critical Care, Melbourne Medical School, University of Melbourne, Melbourne, VIC, Australia.
³ Medical School, Faculty of Medical Sciences, University College London, London.
⁴ Department of Intensive Care, Austin Health, Melbourne, VIC, Australia.
⁵ Royal North Shore Hospital, Malcolm Fisher Department of Intensive Care, St Leonards, NSW, Australia.
⁶ The George Institute for Global Health, Biostatistics and Data Science Division, Barangaroo, NSW, Australia.
⁷ Department of Intensive Care, Hôpital Raymond-Poincare, Garches, France.
⁸ PROMETHEUS IHU, Université Paris-Saclay, Garches, France.
⁹ Laboratory of Infection & Inflammation, School of Medicine Simone Veil Santé, Université Paris-Saclay, Montigny Le Bretonneux, France.
¹⁰ FHU SEPSIS (Saclay and Paris Seine Nord Endeavour to PerSonalize Interventions for Sepsis), Garches, France.
¹¹ Intensive Care Medicine, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia.
¹² Department of Anesthesiology and Intensive Care Medicine, University of Rome La Sapienza, Rome.
¹³ Service d'Anesthésie-Réanimation-Médecine Intensive, Hospices Civils de Lyon, Groupement Hospitalier Sud, Lyon, France.
¹⁴ Department of Anaesthesiology and Intensive Care Medicine, Jena University Hospital, Jena, Germany.
¹⁵ HCor Research Institute, São Paulo, Brazil.
¹⁶ Departments of Medicine, Clinical Epidemiology & Biostatistics (Division of Critical Care), McMaster University, Hamilton, ON, Canada.
¹⁷ Institute for Medical Informatics, Statistics and Epidemiology, Leipzig University, Leipzig, Germany.
¹⁸ Department of Neurology, Tufts University School of Medicine, Boston.
¹⁹ Department of Critical Care Medicine, Beijing Tongren Hospital, Capital Medical University, Beijing.
²⁰ Faculty of Medicine, The University of British Columbia, Vancouver, BC, Canada.
²¹ Department of Intensive Care Medicine, Radboud University Medical Center, Nijmegen, The Netherlands.
²² Anestesiologia e Rianimazione, Università degli Studi di Milano, Milan.
²³ La Casamance Private Hospital, Aubagne, France.
²⁴ Hospital Pablo Tobon Uribe, Medellín, Colombia.
²⁵ School of Science, Western Sydney University, Campbelltown, NSW, Australia.
²⁶ InterSystems Corporation, Cambridge, MA.
²⁷ Faculty of Medicine and Health, Northern Clinical School, The University of Sydney, St Leonards, NSW, Australia.
²⁸ Faculté de Médecine, Université Libre de Bruxelles, Brussels.
²⁹ Office of Research and Education, Canberra Health Services Library, Canberra, ACT, Australia.
³⁰ School of Medicine and Psychology, Australian National University, Canberra, ACT, Australia.
³¹ Division of Intensive Care Medicine, Department of Anesthesiology and Intensive Care, HUS Helsinki University Hospital, Helsinki.
³² Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan.
³³ Erasme University Hospital, Université Libre de Bruxelles, Brussels.
³⁴ Departamento de Clínica Médica-Emergências Clínicas, Faculdade de Medicina da Universidade de São Paulo, São Paulo.
³⁵ CareFlight Australia, Wentworthville, NSW, Australia.
³⁶ Department ICU, The First Affiliated Hospital, Zhejiang Chinese Medical University, Hangzhou, China.
³⁷ Department of Critical Care Medicine, School of Clinical Medicine, Beijing Tsinghua Changgung Hospital, Tsinghua University, Beijing.
³⁸ Department of Business Economics, Health and Social Care, University of Applied Sciences and Arts of Southern Switzerland, Lugano, Switzerland.
³⁹ Department of Clinical Care, University of Bern, Bern, Switzerland.
⁴⁰ Faculty of Medicine and Health, University of New South Wales, Randwick, NSW, Australia.
⁴¹ School of Public Health, Imperial College London, London.

PMID: 38864749
DOI: 10.1056/EVIDoa2400082

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.).

PubMed Disclaimer

Comment in

Intensive Glucose Control in Critically Ill Patients - How Low Do We Go?
Sarma S. Sarma S. NEJM Evid. 2024 Aug;3(8):EVIDe2400196. doi: 10.1056/EVIDe2400196. Epub 2024 Jul 23. NEJM Evid. 2024. PMID: 39041875 No abstract available.

Cited by

Advances in the management of hyperglycaemia and diabetes mellitus during hospitalization.
Idrees T, Castro-Revoredo I, Dhatariya KK, Hernandez L, Umpierrez GE. Idrees T, et al. Nat Rev Endocrinol. 2025 Aug 4. doi: 10.1038/s41574-025-01157-1. Online ahead of print. Nat Rev Endocrinol. 2025. PMID: 40760269 Review.
[S3 guideline on sepsis-prevention, diagnosis, therapy, and follow-up care-update 2025].
Brunkhorst FM, Adamzik M, Axer H, Bauer M, Bode C, Bone HG, Brenner T, Bucher M, David S, Dietrich M, Eckmann C, Elke G, Esser T, Felbinger T, Geffers C, Gerlach H, Grabein B, Gründling M, Günther U, Hagel S, Hecker A, Henkel S, Janusan B, John S, Jörres A, Kaasch A, Kluge S, Kochanek M, Lajca A, Marx G, Mayer K, Meybohm P, Mörer O, Oppert M, Patchev V, Pletz M, Putensen C, Rahmel T, Rosendahl J, Rossaint R, Salzberger B, Sander M, Schaller S, Scharf-Janssen C, Schmitt F, Unterberg M, Weigand M, Weimann A, Weis S, Weiß B, Wolf A, Zarbock A. Brunkhorst FM, et al. Med Klin Intensivmed Notfmed. 2025 Aug 18. doi: 10.1007/s00063-025-01317-1. Online ahead of print. Med Klin Intensivmed Notfmed. 2025. PMID: 40824313 Review. German.
Managing blood glucose in the intensive care unit.
Adigbli DK, Hammond NE, Finfer S. Adigbli DK, et al. Intensive Care Med. 2025 Feb;51(2):442-443. doi: 10.1007/s00134-024-07754-4. Epub 2024 Dec 23. Intensive Care Med. 2025. PMID: 39714614 No abstract available.
Improving Outcomes in Survivors of Sepsis-The Transition from Secondary to Primary Care, and the Role of Primary Care: A Narrative Review.
Taylor R, Vollam S, McKechnie SR, Shah A. Taylor R, et al. J Clin Med. 2025 Apr 9;14(8):2582. doi: 10.3390/jcm14082582. J Clin Med. 2025. PMID: 40283412 Free PMC article. Review.
Management of Diabetes and Hyperglycemia in the Hospital: A Systematic Review of Clinical Practice Guidelines.
Wilson LM, Herzig SJ, Marcantonio ER, Steinman MA, Schonberg MA, Wang BX, Hileman-Kaplan E, Anderson TS. Wilson LM, et al. Diabetes Care. 2025 Apr 1;48(4):655-664. doi: 10.2337/dc24-2510. Diabetes Care. 2025. PMID: 40117466

Publication types

Actions

MeSH terms

Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions

Substances

Actions

LinkOut - more resources

Full Text Sources
- Atypon
- Ovid Technologies, Inc.
Medical
- MedlinePlus Health Information

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

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

Affiliations

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

Authors

Affiliations

Abstract

Comment in

Similar articles

Cited by

Publication types

MeSH terms

Substances

LinkOut - more resources

Full Text Sources

Medical

Abstract

Comment in

Similar articles

Cited by

Publication types

MeSH terms

Substances

Related information

LinkOut - more resources

Full Text Sources

Medical