MONDAY, Oct. 27, 2025 (HealthDay News) -- Intranasal insulin (INI) and empagliflozin are safe and have promising effects on cognition, according to a study published online Oct. 7 in Alzheimer's & Dementia.Jennifer M. Erichsen, from the Wake Forest University School of Medicine in Winston-Salem, North Carolina, and colleagues conducted a phase 2, 2x2 factorial double-blinded randomized trial involving 47 participants with mild cognitive impairment or early Alzheimer disease or who were amyloid-positive. Participants received INI, the sodium-glucose cotransporter-2 inhibitor empagliflozin, both, or placebo for four weeks. Treatment-related adverse events were examined as the primary outcome.The researchers found that for all groups, treatment-related adverse events were mild and similar. They also found an increase in modified Preclinical Alzheimer's Cognitive Composite-5, modulated fractional anisotropy and cerebral blood flow, and reduced plasma glial fibrillary acidic protein with INI. Lower cerebrospinal fluid tau and modulated cerebral blood flow were seen with empagliflozin. Immune/inflammatory/neurovascular markers were moderated by both agents."For the first time, we found that empagliflozin, an established diabetes and heart medication, reduced markers of brain injury while restoring blood flow in critical brain regions. We also confirmed that delivering insulin directly to the brain with a newly validated device enhances cognition, neurovascular health and immune function. Together, these findings highlight metabolism as a powerful new frontier in Alzheimer's treatment," coauthor Suzanne Craft, Ph.D., also from the Wake Forest University School of Medicine, said in a statement.Aptar Pharma provided the intranasal delivery devices.Abstract/Full Text (subscription or payment may be required).Sign up for our weekly HealthDay newsletter