Efficacy and safety of intranasal insulin for postoperative delirium in adults: a meta-analysis of randomized controlled trials

Background: Insulin is commonly used to treat diabetes, but the efficacy of intranasal insulin for the treatment of postoperative delirium (POD) remains unclear. The aim of this study is to assess whether intranasal insulin can reduce the incidence of POD in adult surgical patients. Methods: We searched the PubMed, Web of Science, Embase, and Cochrane Library databases from inception to December 2025. The primary outcome was the incidence of POD. Results: A total of eight randomized controlled trials (RCTs) involving 784 adult surgical patients were included in this meta-analysis. Administration of intranasal insulin was associated with a significant reduction in the incidence of POD within 3 days postoperatively (risk ratio = 0.38; 95% confidence interval: 0.29, 0.50; P < 0.00001; I 2 = 0%), with consistent and robust findings. Sensitivity analysis corroborated the stability of the pooled results. Conversely, no significant effect of intranasal insulin was observed on postoperative serum concentrations of tumor necrosis factor-α and C-reactive protein ( P > 0.05). Safety analyses indicated that intranasal insulin did not significantly alter postoperative fasting blood glucose concentrations (mean difference = 0.04; 95% CI: −0.07, 0.15; P > 0.05; I 2 = 0%), supporting a low risk of hypoglycemia. Conclusion: Intranasal insulin administration may be associated with a reduced incidence of POD in adult surgical patients; however, the current evidence remains preliminary and requires confirmation through larger, multicenter RCTs.