Intranasal Insulin
Insulin, Human (Recombinant) -- Intranasal Administration
The largest Phase 2/3 trial (SNIFF main, n=240) failed its primary cognitive endpoint, and no FDA-approved intranasal insulin product exists. Evidence is strongest for postoperative delirium prevention but mixed for the flagship Alzheimer's/MCI indication.
Insulin sprayed into the nose travels directly along nerve pathways into the brain, where it activates receptors that improve memory, protect brain cells, and reduce inflammation -- all without significantly affecting blood sugar levels. It is being studied for Alzheimer's disease, surgical delirium prevention, and restoring sense of smell.
This entry is a cited research summary, not an established treatment reference. Dosing language is included as source context, not as medical instruction.
Safety Summary
Schmid 2018 safety review (PMID:29508509) encompassing 56 clinical studies (~1,924 participants: 1,092 acute, 832 longer-term up to 9.7 years) reported NO cases of symptomatic hypoglycemia or severe adverse events attributable to intranasal human insulin at standard doses. Most AEs were transient local nasal effects. Dose-dependent hypoglycemia risk profile: 20--80 IU = no clinical hypoglycemia reported in trials (PMID:33721199); up to 160 IU = tolerated without consistent hypoglycemia in perioperative dose-escalation (PMC10897660); 240 IU = hypoglycemia in 2/3 patients in one series (PMC10897660); 600 IU = 2 hypoglycemic events (1 severe at 24 mg/dL, 1 mild at 51 mg/dL) in adaptive dose-escalation study (PMC11573730). Nasal mucosal safety: 4-month human data showed no significant mucosal damage (PMID:3315514); animal studies show insulin promotes nasal mucosal healing (PMID:36384319) and olfactory epithelium protection (PMC8733614). Systemic bioavailability is low (~1--2% without enhancers, ~10--15% with optimized devices; PMC2769806). [.json]
Clinical check-in
If real-world use or exposure is being considered, review potential interactions, contraindications, and monitoring needs with a licensed clinician rather than relying on summary copy alone.
Sources: [1-15]