Introduction: Severe hypoglycemia is one of the most feared adverse outcomes of insulin therapy and requires urgent assistance. The use of currently available glucagon products for rescue treatment of severe hypoglycemia is limited by complex reconstitution steps required before injection, as these products are not stable in solution. As a result, there is compelling evidence that glucagon products are under-prescribed and underused. Dasiglucagon is a stable peptide analog of human glucagon, to be administered via a ready-to-use auto-injector, in development for treatment of severe hypoglycemia.
Methods: In this pivotal Phase 3 trial, the clinical efficacy and safety of 0.6 mg dasiglucagon was compared to placebo and with reference to GlucaGen®. In total, 168 patients with T1D were randomized (2:1:1) and dosed following induced hypoglycemia to reach the glucose target of 55 mg/dL. The primary endpoint was time to PG recovery, defined as first PG increase ≥20 mg/dL after treatment initiation without rescue glucose.
Results: The primary endpoint, time to plasma glucose recovery, was found to be faster for dasiglucagon than placebo. The median time to recovery was 10 min for dasiglucagon vs. 12 and 40 min for GlucaGen® and placebo, respectively (Dasiglucagon vs. Placebo: p<0.001). In the dasiglucagon arm, 65% of patients had recovered within 10 min vs. 49% of patients receiving GlucaGen®. Similarly after 15 min, 99% of patients treated with dasiglucagon had recovered vs. 95% of patients treated with GlucaGen®. There were no serious adverse events in any groups. Nausea and vomiting were reported with similar frequencies for dasiglucagon and GlucaGen® (nausea: 55% and 53%, vomiting: 23% and 19%, respectively).
Conclusion: Dasiglucagon 0.6mg was demonstrated to be a safe, fast and effective treatment option for severe hypoglycemia.
T.R. Pieber: Advisory Panel; Self; ADOCIA, Arecor Limited, AstraZeneca, Novo Nordisk A/S, Sanofi. Speaker's Bureau; Self; Novo Nordisk A/S. U. Hoevelmann: None. J. Willard: None. L. Plum-Moerschel: None. U. Mouritzen: Employee; Self; Zealand Pharma A/S. R. Tehranchi: Employee; Self; Zealand Pharma A/S. R. Aronson: Research Support; Self; AstraZeneca, Becton, Dickinson and Company, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Janssen Pharmaceuticals, Inc., Medtronic, Merck & Co., Inc., Novo Nordisk Inc., Sanofi, Senseonics.