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

Adigbli, Derick; Li, Yang; Hammond, Naomi; Chatoor, Richard; Devaux, Anthony G; Li, Qiang; Billot, Laurent; Annane, Djillali; Arabi, Yaseen; Bilotta, Federico; Bohé, Julien; Brunkhorst, Frank Martin; Cavalcanti, Alexandre Biasi; Cook, Deborah; Engel, Christoph; Green-LaRoche, Deborah; He, Wei; Henderson, William; Hoedemaekers, Cornelia; Iapichino, Gaetano; ... (2024). A Patient-Level Meta-Analysis of Intensive Glucose Control in Critically Ill Adults. (In Press). NEJM Evidence, EVIDoa2400082. NEJM Group 10.1056/EVIDoa2400082

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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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