Dasiglucagon-A Next-Generation Glucagon Analog for Rapid and Effective Treatment of Severe Hypoglycemia: Results of Phase 3 Randomized Double-Blind Clinical Trial

Abstract

Objective: To evaluate the efficacy and safety of dasiglucagon, a ready-to-use, next-generation glucagon analog in aqueous formulation for subcutaneous dosing, for treatment of severe hypoglycemia in adults with type 1 diabetes.

Research design and methods: This randomized, double-blind trial included 170 adult participants with type 1 diabetes, each randomly assigned to receive a single subcutaneous dose of 0.6 mg dasiglucagon, placebo, or 1 mg reconstituted glucagon (2:1:1 randomization) during controlled insulin-induced hypoglycemia. The primary end point was time to plasma glucose recovery, defined as an increase of ≥20 mg/dL from baseline without rescue intravenous glucose. The primary comparison was dasiglucagon versus placebo; reconstituted lyophilized glucagon was included as reference.

Results: Median (95% CI) time to recovery was 10 (10, 10) minutes for dasiglucagon compared with 40 (30, 40) minutes for placebo (P < 0.001); the corresponding result for reconstituted glucagon was 12 (10, 12) minutes. In the dasiglucagon group, plasma glucose recovery was achieved within 15 min in all but one participant (99%), superior to placebo (2%; P < 0.001) and similar to glucagon (95%). Similar outcomes were observed for the other investigated time points at 10, 20, and 30 min after dosing. The most frequent adverse effects were nausea and vomiting, as expected with glucagon treatment.

Conclusions: Dasiglucagon provided rapid and effective reversal of hypoglycemia in adults with type 1 diabetes, with safety and tolerability similar to those reported for reconstituted glucagon injection. The ready-to-use, aqueous formulation of dasiglucagon offers the potential to provide rapid and reliable treatment of severe hypoglycemia.

Trial registration: ClinicalTrials.gov NCT03378635.

Figure 1

One minus Kaplan-Meier plots of time to plasma glucose recovery. Plasma glucose recovery was defined as an increase from baseline of at least 20 mg/dL without rescue intravenous glucose. A: Time to plasma glucose recovery. B: Estimated true time to plasma glucose recovery (linear interpolation).

Figure 2

Mean increase in plasma glucose (mg/dL) shown as change from baseline with 95% CIs after a single dose of 0.6 mg dasiglucagon (red), placebo (orange), or 1.0 mg glucagon (gray). The horizontal line represents the definition of plasma glucose recovery used for the primary end point (an increase from baseline of at least 20 mg/dL).