Consilium Medicum · May 31, 2026

Intranasal insulin in the correction of cognitive impairments with central insulin resistance. A review

By Isaeva RA, Alimetova ZR

The discovery of high concentrations of insulin receptors in the brain has refuted the notion of the central nervous system as an insulin-independent organ and laid the foundation for the concept of central insulin signaling. Currently, insulin has been shown to modulate neuronal activity, synaptic plasticity, memory, and metabolism. Conversely, insulin deficiency or resistance leads to cognitive impairments, as demonstrated in type 2 diabetes mellitus (T2DM), Alzheimer's disease (AD), and other pathologies. It has been established that central insulin resistance in T2DM is not always secondary to peripheral resistance and can arise independently, as observed in AD. This review provides a detailed analysis of the prospects of intranasal insulin administration (INI) as an innovative method for direct cerebral delivery of insulin, bypassing the blood-brain barrier via olfactory pathways. This approach leverages the anatomical feature of the olfactory epithelium, where a fully formed the blood-brain barrier is absent, allowing insulin molecules to penetrate directly into the brain through perineuronal spaces of olfactory nerve axons and the vascular network of the olfactory bulb. The key advantages of INI include minimal systemic absorption, which minimizes peripheral effects, and the complete absence of hypoglycemia risk even with repeated administration, unlike subcutaneous or intravenous injections. Randomized controlled trials convincingly confirm the efficacy of INI: in patients with T2DM, improvements in memory and perfusion in the insular cortex are observed; in AD, acceleration of gait, enhanced cerebral blood flow, improved resting-state functional connectivity, reduced HOMA-IR index, and preservation of cognitive functions are noted; additionally, motor progress in Parkinson's disease and reduced incidence of postoperative cognitive dysfunction are demonstrated. INI is positioned as an innovative strategy to reduce central insulin resistance and improve cognitive functions in various patient populations. However, despite promising results from preliminary randomized controlled trials demonstrating the safety, tolerability, and therapeutic potential of INI, further studies are required for its full integration into clinical practice.

doi.org/10.26442/20751753.2026.4.203632 Open access Interventions