Effect of hyperglycemia at admission on outcomes of intravenous thrombolysis: a systematic review and meta-analysis

Abstract

Background: Acute ischemic stroke (AIS) is a leading cause of disability and mortality worldwide. Intravenous thrombolysis (IVT) improves functional outcomes when administered within the recommended time window; however, treatment response varies among patients. Admission hyperglycemia is common in acute stroke and may negatively influence outcomes. Experimental and clinical data have suggested that elevated glucose levels may exacerbate ischemic injury, impair reperfusion and increase the risk of hemorrhagic transformation. Its prognostic impact after IVT, however, remains unclear. Objective: To systematically evaluate the impact of admission hyperglycemia on hemorrhagic complications, functional outcomes, and mortality in patients with acute ischemic stroke treated with intravenous thrombolysis. Methods: This systematic review was conducted according to the Cochrane Collaboration Handbook and PRISMA guidelines, with protocol registration in PROSPERO (CRD420251270330). PubMed, Embase, Cochrane, Web of Science, and Scopus were searched from inception to December 2025. We included peer-reviewed studies enrolling patients with ischemic stroke treated with IVT that compared hyperglycemia versus normoglycemia at admission and reported at least one outcome of interest. The primary outcomes were any intracranial hemorrhage (aICH), symptomatic intracranial hemorrhage (sICH) and favorable functional outcome (modified Rankin Scale [mRS] 0–2). Secondary outcomes included mortality. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using a Mantel–Haenszel random-effects model. Results: Twenty-one studies comprising 86,313 patients were included (30,555 hyperglycemia; 55,758 normoglycemia). Hyperglycemia was associated with higher odds of any ICH (OR 1.55; 95% CI: 1.25–1.91; I²=3.6%; p < 0.0001) and symptomatic ICH (OR 1.44; 95% CI: 1.20–1.73; I²=30.2%; p < 0.0001). At 90 days, hyperglycemia was associated with lower odds of favorable functional outcomes (OR 0.57; 95% CI: 0.48–0.67; I²=73.3%; p < 0.0001). Mortality was significantly increased in the hyperglycemia group (OR 1.99, 95% CI: 1.60–2.47; I²=74.1%; p < 0.0001). Conclusion: Preexisting hyperglycemia has been associated with chronic proinflammatory states and oxidative stress that may disrupt the blood–brain barrier and exacerbate neurovascular injury. This systematic review indicates that admission hyperglycemia in patients undergoing intravenous thrombolysis for acute ischemic stroke is associated with increased risk of intracranial hemorrhage, worse functional outcomes and increased mortality. Although causality cannot be inferred from the predominantly observational evidence, these findings support the prognostic relevance of admission glycemic status in this population. Further prospective studies are warranted to determine whether specific glycemic thresholds or management strategies might influence outcomes in this setting.