Introduction
Gvoke (glucagon injection) is a ready-to-use glucagon analog formulation indicated for the treatment of severe hypoglycemia in pediatric and adult patients with diabetes. Unlike traditional glucagon emergency kits that require reconstitution, Gvoke comes as a prefilled auto-injector or syringe, making it easier for caregivers to administer during emergency situations.
Mechanism of Action
Gvoke contains glucagon, a polypeptide hormone that acts as a counter-regulatory hormone to insulin. It raises blood glucose levels through multiple mechanisms:
- Stimulates hepatic glycogenolysis (breakdown of glycogen to glucose)
- Activates gluconeogenesis (production of glucose from non-carbohydrate sources)
- Inhibits glycogen synthesis
- Stimulates lipolysis and ketogenesis
Glucagon binds to specific glucagon receptors on hepatocytes, activating adenylate cyclase and increasing intracellular cyclic AMP, which subsequently activates phosphorylase kinase, leading to glycogen breakdown.
Indications
FDA-approved for:
- Treatment of severe hypoglycemia in adults and pediatric patients with diabetes aged 2 years and older
- Use in both insulin-dependent type 1 and type 2 diabetes patients
Dosage and Administration
Available formulations:- Gvoke HypoPen: 0.5 mg/0.1 mL and 1 mg/0.2 mL auto-injectors
- Gvoke PFS: Prefilled syringe (0.5 mg/0.1 mL and 1 mg/0.2 mL)
- Adults and pediatric patients ≥12 years: 1 mg subcutaneous injection
- Pediatric patients 2 to <12 years: 0.5 mg subcutaneous injection
- May repeat in 15 minutes if needed
- Inject into abdomen, thigh, or outer upper arm
- No need for reconstitution
- Train caregivers on proper administration technique
- Store at room temperature (do not refrigerate after opening)
- Renal impairment: No dosage adjustment required
- Hepatic impairment: Use with caution (may have reduced response)
Pharmacokinetics
Absorption: Rapidly absorbed after subcutaneous administration- Time to peak concentration: Approximately 30 minutes
- Bioavailability: Comparable to intramuscular glucagon
- Volume of distribution: Approximately 0.25 L/kg
- Does not significantly cross the blood-brain barrier or placenta
- Undergoes proteolytic degradation
- Half-life: Approximately 8-18 minutes
- Clearance: Rapid, primarily renal
Contraindications
- Hypersensitivity to glucagon or any component of the formulation
- Pheochromocytoma (due to risk of catecholamine release)
- Insulinoma (may cause hypoglycemia)
- Glucagonoma (may worsen condition)
Warnings and Precautions
Hepatic impairment: May have diminished response due to reduced glycogen stores Cardiac effects: Use with caution in patients with cardiac disease (may increase heart rate and blood pressure) Hypersensitivity reactions: Including anaphylaxis; have emergency treatment available Gastrointestinal effects: May cause nausea and vomiting, position patient to avoid aspiration Rebound hypoglycemia: Monitor for recurrence of hypoglycemia after treatment Pregnancy: Category B - Use only if clearly needed Lactation: Glucagon is a large peptide unlikely to be excreted in breast milkDrug Interactions
Beta-blockers: May blunt the hyperglycemic effect of glucagon Indomethacin: May antagonize glucagon's effect on glucose elevation Anticholinergic agents: May increase gastrointestinal side effects Warfarin: Glucagon may enhance anticoagulant effect Insulin: Antagonizes glucagon's hyperglycemic effectAdverse Effects
Common (≥10%):- Nausea (38%)
- Vomiting (17%)
- Headache (15%)
- Injection site reactions (11%)
- Diarrhea
- Dizziness
- Fatigue
- Increased blood pressure
- Tachycardia
- Hypersensitivity reactions
- Anaphylaxis
- Hypokalemia
- Hypertension crisis
Monitoring Parameters
- Blood glucose levels before and after administration
- Vital signs (blood pressure, heart rate)
- Signs of recurrent hypoglycemia
- Injection site reactions
- Electrolytes in prolonged or repeated use
- Response to therapy (time to resolution of hypoglycemic symptoms)
Patient Education
When to use: For severe hypoglycemia when patient cannot take oral carbohydrates Recognition of symptoms: Confusion, seizures, unconsciousness Administration training: Practice with trainer device, proper injection technique After administration:- Turn patient on side to prevent aspiration if vomiting occurs
- Administer oral carbohydrates once patient is alert and able to swallow
- Seek emergency medical attention after use
References
1. FDA Prescribing Information: Gvoke (glucagon injection). Xeris Pharmaceuticals, Inc. 2021. 2. Haymond MW, Schreiner B. Mini-dose glucagon for treatment of mild hypoglycemia in adults with type 1 diabetes: a randomized, double-blind, placebo-controlled crossover study. Diabetes Care. 2017;40(2):234-239. 3. Rickels MR, et al. Low-dose glucagon for prevention of hypoglycemia in adults with type 1 diabetes: a randomized clinical trial. JAMA. 2020;323(14):1403-1413. 4. Sherr JL, et al. Glucagon delivery and automated insulin delivery in type 1 diabetes. Endocrinol Metab Clin North Am. 2020;49(1):145-161. 5. American Diabetes Association. Standards of Medical Care in Diabetes—2023. Diabetes Care. 2023;46(Suppl 1):S1-S291. 6. Pieber TR, et al. Efficacy and safety of dasiglucagon for treatment of hypoglycemia in adults with type 1 diabetes. J Clin Endocrinol Metab. 2020;105(3):dgz157.