Safety of Intranasal Insulin in Type 2 Diabetes on Systemic Insulin: A Double-Blinded Placebo-Controlled Sub-Study of Memaid Trial.

Aims: To determine safety of intranasal insulin (INI) in MemAID trial participants with diabetes treated with systemic insulins.

Materials and methods: This randomized, double-blinded trial consisted of 24-week INI or placebo treatment once daily and 24-week follow-up. Safety outcomes were: 1) Short-term effects on glycemic variability, hypoglycemic episodes on continuous glucose monitoring (CGM) at baseline and on-treatment. 2) Long-term effects on glucose metabolism and weight on INI/placebo treatment and post-treatment follow-up. Of 86 screened subjects, 14 were randomized, 9 (5 INI, 4 Placebo) completed CGM at baseline and on-treatment, and 5 (2 INI, 3 Placebo) completed treatment and follow-up.

Results: INI was safe and was not associated with serious adverse events, hypoglycemic episodes or weight gain. INI administration did not acutely affect capillary glucose. Glycemic variability on CGM decreased with INI, compared to baseline. On INI treatment, there was a long-term trend toward lower HbA1c, plasma glucose and insulin. No interactions with subcutaneous insulins were observed.

Conclusions: INI is safe in older people with diabetes treated with systemic insulins, and it is not associated with adverse events, hypoglycemia or weight gain. Future studies are needed to determine whether INI administration can reduce glycemic variability, improve insulin sensitivity and thus potentially lessen diabetes burden in this population.