Intranasal Glucagon for Treatment of Insulin-Induced Hypoglycemia in Adults With Type 1 Diabetes - A Randomized Crossover Noninferiority Study

This randomized crossover clinical trial, conducted across eight North American centers by the T1D Exchange group, evaluated whether intranasal glucagon powder (3 mg) could replace reconstituted intramuscular glucagon (1 mg) for emergency treatment of hypoglycemia in adults with type 1 diabetes. The clinical context is central: traditional IM glucagon requires immediate reconstitution before injection, a process prone to errors during crisis situations by lay caregivers.

A total of 75 adults with type 1 diabetes were enrolled (mean age 33 years, median diabetes duration of 18 years), each receiving both formulations in separate sessions after hypoglycemia induction by intravenous insulin. The primary outcome was therapeutic success rate, defined as glucose elevation to ≥70 mg/dL or ≥20 mg/dL increase from nadir within 30 minutes.

Results demonstrated practically equivalent efficacy: success criteria were met in 98.7% of intranasal administrations versus 100% of intramuscular. Mean time to success was slightly longer for the intranasal route (16 versus 13 minutes, p<0.001), a difference considered clinically inconsequential by the authors, especially when considering the time and errors involved in reconstituting the IM product. Nausea and mild facial discomfort were the most common adverse events, in similar proportions between routes.

This study served as the basis for FDA approval of Baqsimi in 2019, the first nasal glucagon approved for treatment of severe hypoglycemia. It represents a significant practical improvement: it eliminates the need for technical manipulation of the product in emergency situations, expanding access to hypoglycemic rescue by untrained caregivers.