Age Ageing. 2025 Aug 29;54(10):afaf276. doi: 10.1093/ageing/afaf276.
ABSTRACT
BACKGROUND: Delirium affects up to 25% of hospitalised older patients; however, there are no effective pharmacological treatments. Accumulating evidence of brain insulin resistance and altered cerebral glucose metabolism during delirium present a promising therapeutic target.
OBJECTIVE: To assess the safety and efficacy of intranasal insulin in the treatment of delirium.
DESIGN: Single-centre, randomised, double-blind, placebo-controlled trial.
SETTING: Two geriatric medicine wards in a tertiary hospital.
PARTICIPANTS: 100 patients aged over 64 years presenting to hospital and admitted under geriatric medicine with delirium.
INTERVENTIONS: Participants were randomised in a 1:1 ratio to receive 20 IU of long-acting insulin or placebo intranasally twice daily until delirium resolution, hospital discharge or intervention futility defined by prespecified criteria.
MAIN OUTCOME: The primary outcome was delirium duration, assessed daily using the Confusion Assessment Method. Secondary outcomes included acute length of stay (LOS), delirium severity, antipsychotic use, hospital complications and mortality.
RESULTS: The intention-to-treat analysis included 97 participants [intranasal insulin n = 48, control n = 49; mean (SD) age, 87.6 (7.0) years; 63% female]. Baseline characteristics were similar between groups. Median delirium duration [days (IQR)] was 4.8 [2.9, 9.2] for intranasal insulin and 6.8 [4.0, 9.8] for the control (HR 0.7, 95% CI 0.43-1.15; P = .16). Median acute LOS (days) was 7.9 [4.6, 14.5] for intranasal insulin and 12.9 [6.9, 16.8] for the control (HR 0.56, 0.35-0.89; P = .014). No significant differences were observed in other secondary outcomes. Intranasal insulin demonstrated favourable tolerability. Overall, 86% of the participants were compliant with the intervention (≥80% of doses). Prespecified subgroup analysis revealed an age-related response, with participants aged ≤88 years showing shorter delirium duration with intranasal insulin [n = 46; intranasal insulin: median 3.9 (IQR 2.9, 6.9) days vs control: 7.0 (4.7, 9.7); HR 0.34, 0.16-0.74; P = .006], whereas no difference was observed in participants aged >88 years [n = 51; intranasal insulin 5.4 (2.9, 11.1) vs control 4.9 (2.6, 12.9); HR 0.87, 0.39-1.94; P = .73].
CONCLUSION AND RELEVANCE: This is the first study of intranasal insulin for delirium treatment. The reduced LOS combined with the observed age-related effects warrants further investigation into the clinical potential of intranasal insulin in managing delirium in older patients.
TRIAL REGISTRATION: ACTRN 12618000318280.
PMID:41091693 | DOI:10.1093/ageing/afaf276
