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

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posted on 22.04.2021, 16:26 by Thomas R Pieber, Ronnie Aronson, Ulrike Hövelmann, Julie Willard, Leona Plum-Mörschel, Kim M. Knudsen, Benedikte Bandak, Ramin Tehranchi
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 randomized to receive a single subcutaneous dose of dasiglucagon 0.6 mg, placebo, or reconstituted glucagon 1 mg (2:1:1 randomization) during controlled insulin-induced hypoglycemia. The primary endpoint 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 to 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 minutes 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 minutes after dosing. The most frequent side effects were nausea and vomiting, as expected for glucagon treatment.

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

Funding

The trial was funded by Zealand Pharma.

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