Efficacy of intranasal insulin in preventing postoperative delirium and its impact on insulin resistance in elderly non-cardiac surgical patients: a systematic review and meta-analysis.

BACKGROUND: Postoperative delirium (POD) is a common and serious complication in elderly patients and has been established to be associated with insulin resistance (IR), a key marker of dysregulated glucose metabolism. Therefore, this study aims to systematically evaluate the efficacy of intranasal insulin in preventing POD in elderly non-cardiac surgery patients and to further investigate whether its mechanism of action is related to the improvement of IR. METHODS: A systematic literature search was conducted in PubMed, Embase, the Cochrane Library, Web of Science, China National Knowledge Infrastructure, Wan Fang Database, Chinese Scientific Journals Database and Chinese Biomedical Literature Database from inception to October 19, 2025, to identify randomized controlled trials that compared elderly patients who were administered intranasal insulin during the perioperative period with those who were not. The primary outcomes of this study were the incidence of POD and the efficacy of different insulin dosing regimens. The secondary outcome was the change in the Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) values before and after surgery. Data from eligible trials were pooled to calculate the combined risk ratio (RR) or standardized mean difference (SMD). RESULTS: Analysis of seven trials involving 778 elderly patients showed that, compared to placebo, intranasal insulin significantly reduced POD incidence on day one (RR: 0.33; 95%CI: 0.22 to 0.47; P<0.001) and its cumulative incidence over three days (RR: 0.31; 95%CI: 0.22 to 0.44; P<0.001) and five days (RR: 0.32; 95%CI 0.18 to 0.56; P<0.001). In contrast, the change in HOMA-IR across the surgery period did not differ significantly between the two groups (SMD: -0.27; 95%CI: -0.77 to 0.23; P=0.290). CONCLUSIONS: Intranasal insulin is effective in reducing the incidence of POD. This benefit is likely mediated through central nervous system glucose metabolism, rather than by reversing peripheral IR, a premise that requires validation in future trials.