Identification

Summary

Dasiglucagon is a glucagon analog used to treat severe hypoglycemia in pediatric and adult patients with diabetes.

Brand Names
Zegalogue
Generic Name
Dasiglucagon
DrugBank Accession Number
DB15226
Background

Dasiglucagon is a glucagon analog that acts to increase blood sugar levels.5 It consists of 29 amino acids similar to endogenous glucagon; however, it contains seven substituted amino acids for improved physical and chemical stability in its drug formulation.6 In March 2021, the FDA approved dasiglucagon to treat severe hypoglycemia in patients six years and older with diabetes. It is available as a subcutaneous injection marketed as ZEGALOGUE.5

Severe hypoglycemia is an acute, life-threatening medical condition resulting from a profound drop in blood glucose levels. It is characterized by neurological impairment, with manifestations like loss of consciousness and seizure. Hypoglycemia is a common side effect of antidiabetic treatments, most notably insulin and sulfonylureas. Although it tends to be more common in type 1 diabetes mellitus, occurring in about 22% to 46% of patients annually, about 7% to 25% of patients with type 2 diabetes mellitus treated with insulin experience severe hypoglycemia a year.6 Even with close monitoring of blood glucose levels, it is not always possible to prevent severe hypoglycemic events in patients with diabetes, and children are particularly at risk for experiencing severe hypoglycemia.7 Treatments for severe hypoglycemia have mostly been limited to intravenous dextrose and different glucagon formulations.6 The approval of dasiglucagon marks the first glucagon analog approved for severe hypoglycemia treatment that does not require administration by a healthcare professional.6

Type
Biotech
Groups
Approved, Investigational
Biologic Classification
Protein Based Therapies
Hormones
Protein Chemical Formula
C152H222N38O50
Protein Average Weight
3382.0 Da (anhydrous, free-base form)
Sequences
Not Available
Synonyms
  • Dasiglucagon

Pharmacology

Indication

Dasiglucagon is an antihypoglycemic agent indicated for the treatment of severe hypoglycemia in pediatric and adult patients with diabetes aged 6 years and above.5

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Associated Conditions
Contraindications & Blackbox Warnings
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Pharmacodynamics

Dasiglucagon works to increase blood glucose levels under normal and hypoglycemic conditions.2 After administration of dasiglucagon in adult patients with type 1 diabetes, the mean glucose increase from baseline at 90 minutes was 168 mg/dL. In pediatric patients with type 1 diabetes aged seven to 17 years, the mean glucose increase at 60 minutes after administration of dasiglucagon was 162 mg/dL.5

Mechanism of action

Dasiglucagon is an analog of glucagon, which is a peptide hormone responsible for increasing blood glucose levels. It has the same mechanism of action as endogenous glucagon by acting as an agonist at glucagon receptors, which are G-coupled receptors expressed throughout the body. Dasiglucagon binds to glucagon receptors in the liver, which activates Gsα and Gq, and consequently, adenylate cyclase. Adenyl cyclase increases intracellular cyclic AMP, which stimulates glycogenolysis and glucogenesis in the liver.3,4 As glucose is primarily released from liver glycogen stores, hepatic stores of glycogen are crucial for dasiglucagon to exert its antihypoglycemic effects.5

TargetActionsOrganism
AGlucagon receptor
agonist
Humans
Absorption

Following subcutaneous administration of 0.6 mg dasiglucagon, the mean peak plasma concentration was 5110 pg/mL (1510 pmol/L). Tmax was 35 minutes. In pediatric patients with type 1 diabetes, the mean peak plasma concentration of 3920 pg/mL occurred at around 21 minutes.5 Dasiglucagon has a higher absorption rate than traditional reconstituted glucagon.2

Volume of distribution

The mean apparent volume of distribution ranged from 47 L to 57 L after subcutaneous administration.5

Protein binding

Not Available

Metabolism

Like endogenous glucagon, dasiglucagon undergoes proteolytic degradation pathways in blood, liver, and kidney.5

Route of elimination

Not Available

Half-life

The half-life was approximately 30 minutes following subcutaneous administration.5 Dasiglucagon has a longer plasma elimination half-life than traditional reconstituted glucagon.2

Clearance

Not Available

Adverse Effects
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Toxicity

Overdose may be characterized by nausea, vomiting, inhibition of gastrointestinal tract motility, increased blood pressure, and elevated heart rate. In case of a suspected overdose, serum potassium may decrease so monitoring and correcting of potassium levels may be warranted. A marked increase in blood pressure may be managed by the short-term use of phentolamine mesylate. Appropriate supportive treatment should be initiated.5

Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AcebutololAcebutolol may increase the hypotensive activities of Dasiglucagon.
AceclofenacThe therapeutic efficacy of Dasiglucagon can be decreased when used in combination with Aceclofenac.
AcemetacinThe therapeutic efficacy of Dasiglucagon can be decreased when used in combination with Acemetacin.
Acetylsalicylic acidAcetylsalicylic acid may decrease the antihypertensive activities of Dasiglucagon.
AlclofenacThe therapeutic efficacy of Dasiglucagon can be decreased when used in combination with Alclofenac.
AldesleukinAldesleukin may increase the hypotensive activities of Dasiglucagon.
AlfentanilAlfentanil may decrease the antihypertensive activities of Dasiglucagon.
AlfuzosinAlfuzosin may increase the hypotensive activities of Dasiglucagon.
AliskirenAliskiren may increase the hypotensive activities of Dasiglucagon.
AlmotriptanAlmotriptan may decrease the antihypertensive activities of Dasiglucagon.
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Food Interactions
No interactions found.

Products

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Product Ingredients
IngredientUNIICASInChI Key
Dasiglucagon hydrochlorideYQX12245A9Not AvailableNot applicable
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
ZegalogueInjection, solution0.6 mg/0.6mLSubcutaneousZealand Pharma US, Inc2021-04-05Not applicableUS flag
ZegalogueInjection, solution0.6 mg/0.6mLSubcutaneousZealand Pharma US, Inc2021-04-05Not applicableUS flag

Categories

Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
Not Available
Kingdom
Organic Compounds
Super Class
Organic Acids
Class
Carboxylic Acids and Derivatives
Sub Class
Amino Acids, Peptides, and Analogues
Direct Parent
Peptides
Alternative Parents
Not Available
Substituents
Not Available
Molecular Framework
Not Available
External Descriptors
Not Available
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
AD4J2O47FQ
CAS number
1544300-84-6

References

General References
  1. Battelino T, Tehranchi R, Bailey T, Dovc K, Melgaard A, Yager Stone J, Woerner S, von dem Berge T, DiMeglio L, Danne T: Dasiglucagon, a next-generation ready-to-use glucagon analog, for treatment of severe hypoglycemia in children and adolescents with type 1 diabetes: Results of a phase 3, randomized controlled trial. Pediatr Diabetes. 2021 Aug;22(5):734-741. doi: 10.1111/pedi.13220. Epub 2021 Jun 9. [Article]
  2. Xu B, Tang G, Chen Z: Dasiglucagon: an effective medicine for severe hypoglycemia. Eur J Clin Pharmacol. 2021 Dec;77(12):1783-1790. doi: 10.1007/s00228-021-03183-0. Epub 2021 Jul 5. [Article]
  3. Jiang G, Zhang BB: Glucagon and regulation of glucose metabolism. Am J Physiol Endocrinol Metab. 2003 Apr;284(4):E671-8. [Article]
  4. Morris CH, Baker J: Glucagon . [Article]
  5. FDA Approved Drug Products: ZEGALOGUE (dasiglucagon) injection, for subcutaneous use (March 2021) [Link]
  6. FDA Center for Drug Evaluation and Research: Summary Review for Dasiglucagon [Link]
  7. GlobeNewsWire: Zealand Pharma Announces FDA Approval of Zegalogue® (dasiglucagon) injection, for the Treatment of Severe Hypoglycemia in People with Diabetes [Link]
RxNav
2535233
Wikipedia
Dasiglucagon

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
3CompletedTreatmentCongenital Hyperinsulinism (CHI)1
3CompletedTreatmentHypoglycemia1
3CompletedTreatmentHypoglycemia / Type 1 Diabetes Mellitus4
3Enrolling by InvitationTreatmentCongenital Hyperinsulinism (CHI)1
3Not Yet RecruitingTreatmentHypoglycemia1
2Active Not RecruitingTreatmentHyperinsulinemic Hypoglycemia / Postprandial Hypoglycemia1
2CompletedTreatmentHyperinsulinemic Hypoglycemia / Postprandial Hypoglycemia1
2CompletedTreatmentHypoglycemia / Type 1 Diabetes Mellitus2
2CompletedTreatmentType 1 Diabetes Mellitus2
2Not Yet RecruitingOtherType 1 Diabetes Mellitus1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
Injection, solutionSubcutaneous0.6 mg/0.6mL
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
US10442847No2019-10-152035-02-03US flag

Properties

State
Solid
Experimental Properties
Not Available

Targets

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Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Agonist
General Function
Peptide hormone binding
Specific Function
G-protein coupled receptor for glucagon that plays a central role in the regulation of blood glucose levels and glucose homeostasis. Regulates the rate of hepatic glucose production by promoting gl...
Gene Name
GCGR
Uniprot ID
P47871
Uniprot Name
Glucagon receptor
Molecular Weight
54008.44 Da
References
  1. Battelino T, Tehranchi R, Bailey T, Dovc K, Melgaard A, Yager Stone J, Woerner S, von dem Berge T, DiMeglio L, Danne T: Dasiglucagon, a next-generation ready-to-use glucagon analog, for treatment of severe hypoglycemia in children and adolescents with type 1 diabetes: Results of a phase 3, randomized controlled trial. Pediatr Diabetes. 2021 Aug;22(5):734-741. doi: 10.1111/pedi.13220. Epub 2021 Jun 9. [Article]
  2. FDA Approved Drug Products: ZEGALOGUE (dasiglucagon) injection, for subcutaneous use (March 2021) [Link]
  3. FDA Center for Drug Evaluation and Research: Summary Review for Dasiglucagon [Link]

Drug created at May 20, 2019 15:01 / Updated at November 21, 2021 16:25