Effect of intranasal insulin on postoperative delirium: A systematic review and dose–response meta-analysis

Objective Postoperative delirium (POD) is a common neurological complication associated with adverse clinical outcomes. Intranasal insulin may improve cognitive function, but its effectiveness and optimal dose for preventing POD remain uncertain. We evaluated the effect of intranasal insulin on POD and explored its dose–response relationship. Review methods PubMed, Scopus, Web of Science, and the Cochrane Library were searched through November 2025. Randomised controlled trials comparing intranasal insulin with placebo in adult surgical patients were included. Random-effect pairwise and one-stage dose–response meta-analyses were performed. Risk of bias was assessed using the Cochrane Risk of Bias 2 tool, and certainty of evidence was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation framework. Results Eight randomised controlled trials involving 892 patients were included (502 receiving intranasal insulin and 390 receiving placebo). Intranasal insulin probably reduces POD (moderate-certainty evidence) compared with placebo (risk ratio, 0.39; 95% confidence interval, 0.29–0.51). Subgroup analyses found no significant differences according to surgery type or anaesthetic technique. A dose–response analysis demonstrated a nonlinear association, with a rapid reduction in POD risk at lower doses and the greatest modelled benefit at 30 IU (risk ratio, 0.39; 95% confidence interval, 0.29–0.53). The dose–response curve plateaued above 30 IU, with no additional reduction in POD risk at higher doses. Seven trials had a low risk of bias, while one raised some concerns because of bias in measurement of the outcome. Conclusions Intranasal insulin probably reduces POD in adult surgical patients. The dose–response findings suggest that 30 IU may provide the greatest benefit, with no apparent additional reduction at higher doses. Larger multicentre trials are needed to confirm the optimal regimen and comprehensively evaluate safety.