193-OR: Memory Advancement with Intranasal Insulin in Type 2 Diabetes: Randomized Control Trial

Type 2 diabetes mellitus (T2DM) increases the risk of dementia. Intranasal insulin (INI) has emerged as treatment for T2DM-related cognitive impairment. This randomized, doubled blind trial consisted of 24-week treatment with 40 IU of intranasal insulin (Novolin® R) or placebo (sterile saline) once daily and 24-week follow-up period. T2DM and control participants > 50 years old and able to walk for 6 minutes, were enrolled. The primary outcomes were INI effect on cognition and normal and dual task walking. A total of 244 participants (122 women; 65.8 ± 9.1 years old) were randomized in the four groups (57 DM-INI, 58 DM-Placebo, 65 Control-INI, 64 Control-Placebo). Of 223 at baseline, 174 completed treatment (84 DM [70% of planned enrollment] and 90 controls [100%]), and 156 (69 DM) completed the follow-up. In T2DM, INI did not improve cognitive outcomes or depression as compared to placebo. In controls, INI improved verbal learning during on-treatment (p=0.03) and post-treatment (p=0.03) periods (Mixed Models). DM-INI group had faster normal walking at baseline and on-treatment (p<0.05), and dual task walking at baseline, on-treatment and post-treatment (p<0.05), as compared to DM-placebo. In T2DM, INI treatment increased perfusion in medio-prefrontal cortex (n=8) (p<0.001) measured using pseudo-continuous arterial spin labeling on 3T MRI. There were no clinically significant adverse events related to treatment. This was the Phase 2 Trial, thus the research design was not sufficiently powered to determine efficacy. On-INI improvement of normal and dual-task walking of ~ 5cm/s in T2DM participants and improvement of cognitive function in INI-treated controls are clinically significant and warrant further investigation (NCT02415556).