Ready-to-use Dasiglucagon Injection as a Rapid and Effective Treatment for Severe Hypoglycemia

Abstract

Background: Severe hypoglycemia (SH) is an all too common and feared complication of insulin therapy and necessitates urgent medical intervention. Dasiglucagon, a novel peptide analog of human glucagon, is uniquely stable in aqueous solutions and is currently in development for treatment of SH via a ready-to-use auto-injector. Objective: To assess the efficacy and safety of dasiglucagon injection as a rapid and dependable treatment for SH. Methods: In the pivotal Phase 3 trial, NCT03378635, dasiglucagon (0.6 mg) was compared to placebo, and GlucaGen®, in adults with type 1 diabetes mellitus (N=168), randomized (2:1:1) after insulin-induced hypoglycemia. The primary endpoint was time to plasma glucose (PG) recovery, defined as first PG increase of 20 mg/dL after treatment initiation. Results: The median time to recovery was 10 min for dasiglucagon vs 12 and 40 min for GlucaGen® and placebo, respectively. In the dasiglucagon arm, 65% of patients recovered within 10 min vs 49% receiving GlucaGen®. After 15 min, 99% of dasiglucagon-treated patients recovered vs 95% treated with GlucaGen®. Dasiglucagon was generally well tolerated. Similar frequencies of nausea (55% and 53%), and vomiting (23% and 19%), were reported with dasiglucagon and GlucaGen®, respectively. Injection-site reactions 30 minutes post- dose were reported in 2%, 7%, and 5% of patients in the dasiglucagon, GlucaGen®, and placebo groups, respectively. Conclusions: Dasiglucagon 0.6 mg demonstrated rapid and efficacious treatment for SH. The stability of dasiglucagon in aqueous formulation supports its further development as a unique treatment option for the management of the entire spectrum of mild, moderate, and SH.