By William Elliott, MD, FACP, and James Chan, PharmD, PhD

Dr. Elliott is Assistant Clinical Professor of Medicine, University of California, San Francisco.
Dr. Chan is Associate Clinical Professor, School of Pharmacy, University of California, San Francisco.

The FDA has approved a glucagon analog to treat severe hypoglycemia. Seven of 29 amino acids of native glucagon peptide are substituted, providing improved stability of the peptide in solution. It is marketed as Zegalogue.

INDICATIONS

Dasiglucagon should be prescribed to treat severe hypoglycemia in pediatric and adult patients (≥ age 6 years).1

DOSAGE

The recommended dose is 0.6 mg given subcutaneously.1 If there is no response after 15 minutes, an additional dose may be administered. Dasiglucagon is available as 0.6 mg/0.6 mL single-dose autoinjector or single-dose prefilled syringe.

POTENTIAL ADVANTAGES

Dasiglucagon is soluble and physiochemically stable at physiologic pH vs. native glucagon while still providing the biopotency of glucagon.2 It features ready-to-use preparation and does not require reconstitution.

POTENTIAL DISADVANTAGES

There is a potential for immunogenicity with a modified, nonnative peptide. In clinical trials, four of 498 subjects developed treatment-emergent, antidrug antibodies.1

COMMENTS

The safety and efficacy of dasiglucagon were evaluated in three randomized, double-blind, placebo-controlled trials, two in adults and one in pediatric subjects with type 1 diabetes (age 6 to 17 years).1 Subjects were randomized to dasiglucagon (0.6 mg) or placebo. In one adult trial and in the pediatric trial, glucagon 1 mg was included as an active comparator. Severe hypoglycemia was induced by IV administration of insulin to a target plasma level of glucose < 60 mg/dL in adults and < 80 mg/dL in pediatrics. The primary efficacy endpoint was time to plasma glucose recovery (i.e., increase of ≥ 20 mg/dL) from time of administration without additional intervention within 45 minutes. Plasma levels were assessed periodically at predose and from four to 90 minutes after treatment.

The median times to glucose recovery were 10 minutes for dasiglucagon, 12 minutes for glucagon, and 40 minutes for placebo in the first adult study and 10 minutes and 35 minutes for dasiglucagon and placebo, respectively, for the second adult study. In the pediatric study, median times were 10 minutes for dasiglucagon and glucagon and 30 minutes for placebo. The most frequently reported side effects were nausea, vomiting, and headache, which occurred more frequently in adults than in pediatric subjects.1

In a pharmacokinetic/pharmacodynamic study, dasiglucagon 0.6 mg showed similar time to reach plasma glucose levels ≥ 70 mg/dL and time to increase levels ≥ 20 mg/dL vs. glucagon.3 However, dasiglucagon showed a higher and longer-lasting glucose response, potentially reducing the risk for recurrent hypoglycemia.

CLINICAL IMPLICATIONS

Severe hypoglycemia (< 55 mg/dL) is an acute, potentially life-threatening complication of diabetes. Children with type 1 diabetes on insulin are particularly vulnerable.4 Glucagon is the primary FDA-approved treatment for rescue of severe hypoglycemia.5 Currently, there are two approved rescue glucagon lyophilized powder kits that require reconstitution (GlucaGen Hypokit and Glucagon Emergency Kit). A non-aqueous solution (formulated in an aprotic solvent with dimethylsulfoxide) is available (Gvoke Hypopen), but is associated with more injection site erythema, edema, and discomfort.6 Glucagon also is available as an intranasal preparation (Baqsimi), but produces a slower glycemic response.2

Dasiglucagon provides a ready-to-use injection as an alternative to subcutaneous glucagon. Pricing has not been announced, but the company has stated it plans to offer “parity pricing” with similar products. 

REFERENCES

  1. Zealand Pharma A/S. Zegalogue prescribing information. March 2021.
  2. Li S, Hu Y, Tan X, et al. Evaluating dasiglucagon as a treatment option for hypoglycemia in diabetes. Expert Opin Pharmacother 2020;21:1311-1318.
  3. Hövelmann U, Bysted BV, Mouritzen U, et al. Pharmacokinetic and pharmacodynamic characteristics of dasiglucagon, a novel soluble and stable glucagon analog. Diabetes Care 2018;41:531-537.
  4. Saydah S, Imperatore G, Divers J, et al. Occurrence of severe hypoglycaemic events among US youth and young adults with type 1 or type 2 diabetes. Endocrinol Diabetes Metab 2019;2:e00057.
  5. Centers for Disease Control and Prevention. How to treat low blood sugar (hypoglycemia). Last reviewed Jan. 20, 2021.
  6. Hawkes CP, De Leon DD, Rickels MR. Novel preparations of glucagon for the prevention and treatment of hypoglycemia. Curr Diab Rep 2019;19:97.