Glycemic Control in Severe Acute Brain Injury: Systematic Review and Meta-analysis with Trial Sequential Analysis
In brief
Strict blood-sugar control shows no mortality benefit in severe brain injury
A meta-analysis of 18 randomized trials (3,196 patients) found that targeting tighter glucose levels did not lower death rates compared with liberal targets, and functional outcomes were similarly unchanged. Evidence certainty was low to very low, and no data on quality of life were available, so further high-quality trials are needed.
- Journal
- Neurocritical care (Q1)
- Published
- 20 July 2026
- Study design
- Systematic review / meta-analysis of RCTs
- Evidence level
- Level 1, High (CEBM 1a)
- Authors
- Anne-Sophie Worm Fenger, Markus Harboe Olsen, Helene Ravnholt Jensen, Signe Janum Eskildsen, Lea Rue Honoré, Maria Louise Fabritius, et al.
- PMID
- 42477260
- DOI
- 10.1007/s12028-026-02592-2
Why clinicians should know about it
- Picked for Critical Care and Intensive Care Medicine (top studies of the week, 26 July 2026): Glycemic control meta‑analysis in acute brain injury
Abstract
BACKGROUND: Hyperglycemia is common in intensive care unit (ICU) patients, including those with acute brain injury. Although many studies associate hyperglycemia with increased mortality, the optimal blood glucose target remains uncertain. This systematic review compares strict versus liberal glycemic control in ICU patients with acute brain injury, focusing on all-cause mortality, neurological outcome, and health-related quality of life. METHODS: Two authors independently searched CENTRAL, EMBASE, Medline, Web of Science, CINAHL, and trial registers for studies comparing glycemic control targets. Data were extracted in duplicate with discrepancies resolved by two screeners using Covidence. We performed meta-analysis, trial sequential analysis (TSA), and risk-of-bias assessment, and evaluated certainty of evidence using Grading of Recommendations Assessment, Development and Evaluation (GRADE). RESULTS: From 29,221 records, we included 18 randomized clinical trials (RCTs) (N = 3196 patients) and 13 observational studies (N = 8354 patients). Fixed-effect meta-analysis suggested no effect on mortality from strict compared with liberal control (N = 3196 patients; RR 0.95; 95% CI 0.84-1.08; I2 0%; very low level of evidence), with TSA indicating a need for additional trials. Fixed-effect meta-analysis showed no clear effect on functional outcome (N = 1239 patients; RR 0.91; 95% CI 0.82-1.00; I2 0%; low level of evidence), and TSA indicated evidence against an effect. No studies reported health-related quality of life. CONCLUSIONS: Low to very low certainty evidence suggests there is no difference between strict and liberal glycemic control regarding mortality or functional neurological outcome after severe acute brain injury. While additional large, low-bias RCTs could improve certainty, the benefit from strict glycemic control remains uncertain.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.