Contributor: Seana-Pierre Williams, PharmD Candidate 2025, PCOM Georgia School of Pharmacy
The use of insulin therapy to control elevated glucose levels in patients with diabetes adds a layer of complication in diabetes management due to the potential risk of over-treatment resulting in hypoglycemia. Hypoglycemia, in patients with diabetes, is typically characterized as having a blood glucose level below 70 mg/dL. This subsequent hypoglycemia can have a greater effect on morbidity and mortality for patients with type 1 diabetes, who are reliant on exogenous insulin, and extreme hypoglycemic events are directly associated with substantial overall health care costs.1
Glucagon is a hormone produced by the pancreas that stimulates the liver to release glucose to replenish blood glucose therefore maintaining glucose homeostasis. Historically, exogenous glucagon was supplied as a powder that must be reconstituted into a solution before delivery due to glucagon’s instability in solution. One of the primary challenges in formulating exogenous glucagon is maintaining its stability over time. Glucagon is inherently unstable and can degrade when exposed to various conditions, such as temperature changes, pH fluctuations, and agitation.2 The traditional reconstitution process of glucagon from powder to liquid has been a barrier to swift and efficient administration during emergencies.2 Gvoke HypoPen is an autoinjector device developed by Xeris Pharmaceuticals that provides a convenient and user-friendly way to administer glucagon in cases of severe hypoglycemia and was approved by the FDA in 2019. The medication device is supplied as an auto-injector and prefilled syringe for subcutaneous injection only containing a freeze-dried powder glucagon, a surfactant, an antioxidant and chelating agent combined with a polar liquid to prevent instability. The formulations are available in two premeasured doses: a 0.5 mg/0.1 mL dose for pediatric administration and a 1 mg/0.2 mL dose for adolescent and adult administration. Gvoke (Glucagon) injection is an antihypoglycemic agent indicated for the treatment of severe hypoglycemia in pediatric and adult patients with diabetes ages 2 years and above. Severe hypoglycemia is classified as a blood glucose level below 54 mg/dL and requires immediate treatment.
Potential advantages of Gvoke include the ease of use due to its auto-injection formulation, the absence of need for reconstitution and potentially the time to resolution of hypoglycemia in comparison to other delivery systems such as the Glucagon Emergency Kit (GEK). According to Cummins et al in a phase three comparison of a ready-to-use liquid glucagon rescue pen to glucagon emergency kit for the symptomatic relief of severe hypoglycemia, the auto-injector was shown to have a significantly higher success rate in delivering a full glucagon dose during simulated emergencies with both trained and untrained users. Additional advantages include the presence of a sheath protected needle that retracts into the auto-injector which reduces the incidence of needle sticks, the device can be stored for two years at room temperature and a reduction in injection site pain due to a smaller injected volume. A potential disadvantage of Gvoke is the potential for nausea and vomiting as the nonaqueous solution is delivered subcutaneously.1 Drug interaction considerations include patients who are currently prescribed beta blockers, indomethacin and warfarin. Patients prescribed beta blockers may have a transient increase in pulse and blood pressure, Gvoke may may lose its ability to raise glucose or may produce hypoglycemia with use of indomethacin and risk of increased anticoagulant effects with warfarin.
Key Counseling Points for Patients and Their Caregivers4:
- Be aware of signs and symptoms of hypoglycemia as severe hypoglycemia requires immediate treatment. Administer Gvoke as soon as severe hypoglycemia is recognized
- Signs and symptoms of hypoglycemia include but is not limited to shaking, sweating, fast heartbeat, extreme hunger, confusion, irritability, dizziness and blurred vision.
- Visually inspect the Gvoke product prior to administration. The solution should appear clear and colorless to pale yellow and be free of particles. If the solution is discolored or contains particulate matter, do not use.
- Store medication in its original sealed foil pouch until time of use
- Administer the injection in the lower abdomen, outer thigh, or outer upper arm according to printed instructions for use on packaging. Call for emergency assistance immediately after administering the dose.
- When the patient has responded to treatment, give oral carbohydrates to prevent recurrence of hypoglycemia.
- Do not attempt to reuse Gvoke as each device contains a single dose of glucagon and cannot be reused.
- Allergic reactions can occur with Gvoke therefore seek immediate medical attention if they experience any symptoms of serious hypersensitivity reactions
Accessibility of Gvoke can be influenced by various factors including cost, insurance coverage and patient education. The future of glucagon delivery holds the promise of transforming hypoglycemia management, revolutionizing the way individuals with diabetes respond to low blood sugar episodes. Several avenues of innovation are shaping the future of glucagon administration, aiming to enhance its efficacy, ease of use, and overall patient experience.3
References:
- Damianne Brand-Eubanks; Gvoke HypoPen: An Auto-Injector Containing an Innovative, Liquid-Stable Glucagon Formulation for Use in Severe Acute Hypoglycemia. Clin Diabetes 1 October 2019; 37 (4): 393–394.
- Kumar, Samarth et al. “Glucagon: Delivery advancements for hypoglycemia management.” International journal of pharmaceutics vol. 652 (2024): 123785. doi: 10.1016/j.ijpharm.2024.123785
- Christiansen M, Cummins M, Prestrelski S, Junaidi K. A phase 3 comparison of a ready-to-use liquid glucagon rescue pen to glucagon emergency kit for the symptomatic relief of severe hypoglycemia. Poster presented at the Diabetes Technology Society’s Diabetes Technology Meeting, 8–10 November 2018, Bethesda, Md
- Gvoke-Accessdata.Fda.Gov, www.accessdata.fda.gov/drugsatfda_docs/label/2021/212097Orig1s007lbl.pdf. Accessed 12 Dec. 2024.
