The evolution of glucagon: From emergency glucagon kits and pre-filled syringes to autoinjectors and nasal sprays

Learn about three major advances in treating severe low blood sugar (severe hypoglycemia)

Evolution of Glucagon timeline
Lauren Barr
October 13, 2022

The risk of severe low blood sugar can feel overwhelming for anyone with diabetes using insulin or other diabetes medications known to cause low blood sugar. Also known as severe hypoglycemia, these lows occur when blood sugar drops below a certain level, causing physical and mental changes that can include headache, fatigue, seizures and even loss of consciousness. While hypoglycemia can be treated by eating sugar or a sugar-sweetened product, a severe low requires faster medical treatment — typically with a glucagon injection.

It’s important for diabetes patients, their caretakers and the individuals involved in their day-to-day life to know the signs of severe hypoglycemia — so it can be quickly treated. A medication called glucagon is a potentially life-saving tool for correcting these severe lows.

Who is at risk of a severe low?

For patients with diabetes, those with type 1 diabetes are three times as likely to experience hypoglycemia than those with type 2 diabetes.  You may be at risk of a severe low if you:

  • Take insulin or sulfonylureas
  • Exercise at an intense level
  • Tend to skip meals
  • Have an inconsistent schedule
  • Feel stressed most of the time
  • Have tight blood sugar goals
  • Have insulin pump problems
  • Are more sensitive to insulin


Glucagon’s role in raising blood glucose levels

Glucagon is a hormone that plays a critical role in quickly raising the body’s blood sugar levels to restore balance. It was discovered and studied since 1922. Over time, there have been three major advances in the administration of glucagon for treating severe lows:

1. Emergency glucagon kit
The first glucagon kit became available in 1960. These life-saving kits contain a vial of glucagon powder and a syringe filled with saline. They require preparation time and someone to administer the injection using the syringe. Eli Lilly and Novo Nordisk are two of the largest suppliers of these glucagon emergency kits, although Lilly recently announced that its kit will be discontinued by the end of 2022.

2. Prefilled syringe and nasal spray
As the science behind glucagon injections continued to advance, it became clear that giving diabetes patients and their caregivers an easier, faster way to administer glucagon was necessary. In 2019, pre-filled glucagon syringes became available for adults and children, as well as a needleless nasal spray, which doesn’t require inhalation.

3. Glucagon autoinjector
The most recent advancement in the administration of glucagon comes in the form of an autoinjector, first released in 2020. Gvoke HypoPen® (glucagon injection) is a ready-to-use glucagon injection that can be administered in two steps. Glucagon autoinjectors typically have a simpler administration process than emergency glucagon kits — they don’t require mixing and have no visible needles.

From glucagon kits to autoinjectors, innovation in the treatment of severe lows has made it easier for diabetes patients and their caregivers to manage type 1 diabetes and type 2 diabetes. No matter which glucagon option you choose, the most important thing to remember is to always be prepared — so you can focus more on the people, places and activities that bring you joy.

Gvoke HypoPen
*Store in original sealed pouch until time of use.

Meet Gvoke HypoPen

Gvoke HypoPen is the ready-to-use rescue pen anyone can administer with confidence1

  • In a study with simulated emergency conditions, 99% of people used it correctly1
  • Simple to administer at a moment’s notice, like an epinephrine autoinjector for severe allergic reactions
  • You can even self-administer it in certain situations2
  • Can be administered to the outer upper arm, lower abdomen or outer thigh3
  • Brings very low blood sugar back up quickly and safely3†

†In two clinical studies in adults, blood sugar levels that were less than 50 mg/dL increased to above 70 mg/dL or increased by at least 20 mg/dL within 13.8 minutes on average.


  1. Valentine V, Newswanger B, Prestrelski S, Andre AD, Garibaldi M. Human factors usability and validation studies of a glucagon autoinjector in a simulated severe hypoglycemia rescue situation. Diabetes Technol Ther. 2019;21(9):522-530.
  2. Gvoke HypoPen [instructions for use]. Chicago, IL: Xeris Pharmaceuticals, Inc; 2023.
  3. Gvoke [prescribing information]. Chicago, IL: Xeris Pharmaceuticals, Inc; 2023.
Indication and Important Safety Information⁠—⁠Read More


GVOKE is a prescription medicine used to treat very low blood sugar (severe hypoglycemia) in adults and kids with diabetes ages 2 years and above. It is not known if GVOKE is safe and effective in children under 2 years of age.


Do not use GVOKE if:

  • you have a tumor in the gland on top of your kidneys (adrenal gland), called a pheochromocytoma.
  • you have a tumor in your pancreas called an insulinoma.
  • you are allergic to glucagon or any other inactive ingredient in GVOKE.


High blood pressure
GVOKE can cause high blood pressure in certain people with tumors in their adrenal glands.

Low blood sugar
GVOKE can cause low blood sugar in certain people with tumors in their pancreas called insulinomas by making too much insulin in their bodies.

Serious allergic reaction
Call your doctor or get medical help right away if you have a serious allergic reaction including:

  • rash
  • difficulty breathing
  • low blood pressure


The most common side effects of GVOKE in adults include:

  • nausea
  • vomiting
  • swelling at the injection site
  • headache

The most common side effects of GVOKE in children include:

  • nausea
  • low blood sugar
  • high blood sugar
  • vomiting
  • abdominal pain
  • headache
  • pain or redness at the injection site
  • itching

These are not all the possible side effects of GVOKE. For more information, ask your doctor. Call your doctor for medical advice about side effects.

You are encouraged to report side effects of prescription drugs to the FDA. Visit, or call 1-800-FDA-1088.


Before using GVOKE, tell your doctor about all your medical conditions, including if you:

  • have adrenal gland problems
  • have a tumor in your pancreas
  • have not had food or water for a long time (prolonged fasting or starvation)
  • have low blood sugar that does not go away (chronic hypoglycemia)
  • are pregnant or plan to become pregnant
  • are breastfeeding or plan to breastfeed

Tell your doctor about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.


  • Read the detailed Instructions for Use that come with GVOKE.
  • Use GVOKE exactly how your healthcare provider tells you to use it
  • Make sure your relatives, close friends, and caregivers know where you store GVOKE and how to use it the right way before you need their help.
  • Act quickly. Having very low blood sugar for a period of time may be harmful.
  • Your healthcare provider will tell you how and when to use GVOKE.
  • After giving GVOKE, your caregiver should call for emergency medical help right away.
  • If you do not respond after 15 minutes, your caregiver may give you another dose, if available. Tell your healthcare provider each time you use GVOKE. Low blood sugar may happen again after receiving an injection of GVOKE. Your diabetes medicine may need to be changed.


  • Keep GVOKE in the foil pouch until you are ready to use it.
  • Store GVOKE at temperatures between 68°F and 77°F.
  • Do not keep it in the refrigerator or let it freeze.

Keep GVOKE and all medicines out of the reach of children.

For more information, call 1-877-937-4737 or go to

Please see the Full Prescribing Information for Gvoke