MemAID: Memory advancement with intranasal insulin vs. placebo in type 2 diabetes and control participants: a randomized clinical trial

Background This study aimed at assessing the long-term effects of intranasal insulin (INI) on cognition and gait in older people with and without type 2 diabetes mellitus (T2DM). Methods Phase 2 randomized, double-blinded trial consisted of 24 week treatment with 40 IU of INI (Novolin (R) R, off-label use) or placebo (sterile saline) once daily and 24 week follow-up. Primary outcomes were cognition, normal (NW), and dual-task (DTW) walking speeds. Of 244 randomized, 223 completed baseline (51 DM-INI, 55 DM-Placebo, 58 ControlINI, 59 Control-Placebo; 109 female, 65.8 +/- 9.1; 50-85 years old); 174 completed treatment (84 DM, 90 Controls); 156 completed follow-up (69 DM). Results DM-INI had faster NW (similar to 7 cm/s; p = 0.025) and DTW on-treatment (p = 0.007; p = 0.812 adjusted for baseline difference) than DM-Placebo. Control-INI had better executive functioning on-treatment (p = 0.008) and post-treatment (p = 0.007) and verbal memory post-treatment (p = 0.004) than Control-Placebo. DM-INI increased cerebral blood flow in medio-prefrontal cortex (p < 0.001) on MRI. Better vasoreactivity was associated with faster DTW (p < 0.008). In DM-INI, plasma insulin (p = 0.006) and HOMA-IR (p < 0.013) decreased post-treatment. Overall INI effect demonstrated faster walking (p = 0.002) and better executive function (p = 0.002) and verbal memory (p = 0.02) (combined DM-INI and Control-INI cohort, hemoglobin A1c-adjusted). INI was not associated with serious adverse events, hypoglycemic episodes, or weight gain. Conclusion There is evidence for positive INI effects on cognition and gait. INI-treated T2DM participants walked faster, showed increased cerebral blood flow and decreased plasma insulin, while controls improved executive functioning and verbal memory. The MemAID trial provides proof-of-concept for preliminary safety and efficacy and supports future evaluation of INI role to treat T2DM and age-related functional decline. [GRAPHICS] .

Automated summary

This study investigated the long-term effects of intranasal insulin (INI) on cognition and gait in older individuals, with and without type 2 diabetes mellitus (T2DM). The results showed that INI treatment improved walking speed and cerebral blood flow in T2DM participants, while controls exhibited improved executive functioning and verbal memory. These findings suggest the potential of INI in treating T2DM and age-related functional decline.