Dasiglucagon shown as a promising therapeutic for severe hypoglycemia in a recent phase 3 trial

Published recently in Diabetes Care, a phase 3 study demonstrated the rapid hypoglycemia reversing capability of dasiglucagon among adult patients with type 1 diabetes mellitus (T1DM) who were experiencing severe insulin-induced hypoglycemia.1 Together with the results from similar studies targeting the pediatric population, the United States Food and Drug Administration has recently approved dasiglucagon for the treatment of severe hypoglycemia in people with diabetes aged 6 years or older.2

While T1DM is a chronic autoimmune disease characterized primarily by hyperglycemia caused by a dysfunctional pancreatic βcell-induced insulin deficiency, T1DM patients can often experience weekly episodes of symptomatic hypoglycemia due to defective feedback response towards exogenous insulin.3,4 Currently, glucagon remains the preferred rescue treatment option for insulin-related severe hypoglycemia.5 However, the multiple preparation steps involved and prior training for reconstitution and injection required have made the existing glucagon kits challenging to many users and can be especially risky during hypoglycemic crises.6 Thus, emerging options now have a greater emphasis on formulation stability with high readiness for use that can potentially save the need of urgent reconstitution.7

One such example is dasiglucagon, a readily soluble, physiochemically stable human glucagon analog peptide that is available as a ready-to-use rescue pen.7 While an earlier pharmacokinetic and pharmacodynamic study had preliminarily established dasiglucagon’s comparable effect to standard glucagon with good tolerability, a recent phase 3 study has given a more in-depth investigation to its therapeutic efficacy.1,8

The phase 3 study was a randomized, double-blind, placebo-controlled trial that randomly assigned 170 adults with a mean T1DM duration of 20 years in a 2:1:1 ratio to a single subcutaneous injection of 0.6mg dasiglucagon, placebo, or 1mg reconstituted lyophilized glucagon, under a controlled insulin-induced hypoglycemic state.1,9 Whereas placebo was used as a primary comparator to dasiglucagon, the reconstituted glucagon served as a reference only.1 The primary outcome was the measurement of time to plasma glucose recovery, defined as an increase from baseline of ≥20mg/dL without intravenous rescue glucose.1,9

From the study, patients treated with dasiglucagon achieved a significantly faster median time to recovery versus placebo (10 minutes vs. 40 minutes; p<0.001) that was numerically comparable to reconstituted glucagon (12 minutes).1,9 Moreover, a significantly larger proportion of patients from the dasiglucagon arm achieved plasma glucose recovery within 15 minutes versus placebo (99% vs. 2%; p<0.001) that was also similar to the glucagon arm (95%).1,9 This favorable outcome was also observed in other investigated time points at 10, 20 and 30 minutes post-dose.1,9

In terms of safety, nausea and vomiting were reported as the most frequent adverse effects which were expected from glucagon treatment.1 Overall, dasiglucagon had not only offered rapid and effective reversal of hypoglycemia in adults with T1DM, but also presented a safe and tolerable profile that is akin to standard reconstituted glucagon injection.1 “The results of this trial add significantly to the clinical evidence supporting the use of dasiglucagon for the treatment of severe hypoglycemia, and these data build upon the strong clinical data reported throughout the dasiglucagon’s clinical trial program in this indication,” summarized Professor Thomas Pieber, Head of the Division of Endocrinology and Metabolism and Chairman of the Department of Internal Medicine at Medical University of Graz, Austria. Considering the convincing evidence of dasiglucagon, it can definitely help patients and their caregivers to address severe hypoglycemia.

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