Safety and Efficacy of Tight Versus Loose Glycemic Control in Acute Stroke Patients: A Meta-Analysis of Randomized Controlled Trials

Background: Hyperglycemia is associated with worse stroke outcomes but it is uncertain whether tight glycaemic control during the acute stroke period is associated with a better outcome. We conducted a meta-analysis to compare the effect of tight glycemic control versus loose glycemic control in the acute phase of stroke patients. Methods: A literature search was performed to identify randomized controlled trials (RCTs) comparing the safety and efficacy of tight glycemic control with a relatively loose control of blood glucose of acute stroke (ischemic or hemorrhagic) patients within 24 hours after stroke onset. We required that the blood glucose level of the patients should not be lower than 6.11mmol/L at the time of enrollment, and for the intensive blood glucose control range, we defined the blood glucose level as lower than that of the control group.Tight glycaemic control was defined as blood glucose ≥ 6.11 mmol/L. The primary efficacy outcome measure was deaths from any cause at 90 days. Secondary efficacy outcomes comprised the number of participants with modified Rankin score (mRS), We define mRS scores 0-2 as favorable scores, recurrent stroke, and the National Institute of Health stroke scale (NIHSS) or the European Stroke Scale (ESS) scores. We defined the number of participants with hypoglycemia as our primary safety outcome. Subgroup analysis was performed according to age, the variety of interventions, maintained glucose level, and status of hypoglycemia on NIHSS scores or ESS scores. Results: Fifteen RCTs with 2957 participants meeting the including criteria were identified and included in this meta-analysis, although not all included data on every outcome measure. Data on the primary efficacy endpoint, mortality at 90 days, was available in 11 RCTs a total of 2575 participants. There was no significant difference between the intervention and control groups (OR: 1.00; 95%CI: 0.81 to 1.23; P=0.99). For secondary endpoints, there was no difference between intervention and control groups for a mRS < from 0-2 (OR: 0.96; 95%CI: 0.80 to 1.15; P=0.69; data from 9 RCTs available), or recurrent stroke (OR: 1.34; 95%CI: 0.92 to 1.96; P=0.13; data from 3 RCTs available). For NIHSS scores or ESS scores, there was a small difference in favor of intensive controls (SMD: -0.29; 95%CI: -0.54 to -0.04; P=0.02) There was a marked increase in hypoglycemia with tight control: (OR of 9.46 (95%CI: 4.59 to 19.50; P<0.00001; data from 9 RCTs available) Conclusions: There was no difference between tight and loose glycemic control on mortality, independence, or recurrent stroke outcome in acute stroke, but an increase in hypoglycaemia. There was a small effect improvement on neurological scales but the relevance of this needs confirming in future adequately powered studies.