Materia Medica
Treating Insulin-Induced Hypoglycemia with Confidence: Dasiglucagon (Zegalogue®) Karen M. Fancher, PharmD, BCOP Type 1 diabetes mellitus (T1DM), once known as juvenile diabetes or insulin-dependent diabetes, is a chronic condition in which the pancreas produces little or no insulin.1 When the body does not have enough insulin or cannot use it properly, glucose accumulates in the blood and can result in a variety of shortand long-term health complications.2 Approximately 1.6 million Americans have T1DM, including about 200,000 youth (under 20 years of age) and 1.4 million adults.3 Up to five million people in the United States are expected to have T1DM by 2050, including nearly 600,000 youth. As pancreatic β-cell function declines in patients with T1DM, exogenous insulin is required to achieve glycemic control.4 Administration of exogenous insulin is central to the management of T1DM, but hypoglycemia often occurs; it is estimated that 30-40% of patients with T1DM experience one to three episodes of severe hypoglycemia per year. Severe hypoglycemia requires prompt medical intervention to prevent potentially life-threatening complications such as seizure, loss of consciousness and coma.5 Further, multiple hypoglycemic episodes may have negative longterm consequences on growth and development in pediatric patients.
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Patients with T1DM who experience severe hypoglycemia are typically treated with glucagon, a wellestablished first-line treatment.5,6 The American Diabetes Association treatment guidelines recommend that glucagon is prescribed for all individuals at increased risk for clinically significant hypoglycemia, and pediatric guidelines recommend that an unexpired glucagon rescue kit be readily accessible to all patients and their caregivers.5,7,8 However, native glucagon is unstable and rapidly degrades in aqueous solutions, and therefore commercially available glucagon emergency kits contain a lyophilized powdered glucagon that must be reconstituted using multiple complex steps prior to injection. The reconstitution process represents a significant barrier to timely, accurate and effective administration of this emergency product.5,6,9 Therefore, a stable ready-to-use formulation is of great interest.4 Dasiglucagon (Zegalogue®) is a glucagon analogue with improved solubility and stability in aqueous liquid. Dasiglucagon was approved by the United States Food and Drug Administration in March 2021 for the treatment of severe hypoglycemia in adult patients with diabetes and in pediatric patients with diabetes who are six years of age or older.6,10
Dasiglucagon Dasiglucagon is a novel peptide analogue of human glucagon. It acts as a glucagon receptor agonist, increasing the release of glucose from the liver and stimulating glycogen breakdown. This anti-hypoglycemic effect is dependent on hepatic glycogen stores.6,11 Dasiglucagon is comprised of 29 amino acids, with seven substitutions compared to native glucagon.4 The substitutions result in increased solubility and stability while maintaining specificity for the glucagon receptor.6,9 In addition, it has a higher absorption rate and longer plasma elimination half-life than traditional reconstituted glucagon.12
Clinical Studies The efficacy of dasiglucagon for the treatment of severe hypoglycemia in patients with T1DM was demonstrated in a randomized, double-blind, phase III trial.9 In this study, 170 adult patients with T1DM were randomized 2:1:1 to receive subcutaneous dasiglucagon, reference glucagon (GlucaGen®) or placebo during controlled insulininduced 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 median time to plasma glucose recovery was 10 www.acms.org
