Glucagon

Glucagon is a hormone made by alpha cells in the pancreas that increases blood glucose. Glucagon raises blood sugar by telling the liver to release stored sugar into the bloodstream and make new sugar.

Synthetic glucagon is used to treat severe hypoglycemia, or dangerously low blood sugar. 

Why glucagon is treatment for very low blood glucose

People with diabetes use glucagon to treat severe hypoglycemia. Glucagon is produced naturally in the body when blood sugars drop, while synthetic glucagon is given by injection to raise blood sugars.

Hypoglycemia varies in severity and can occur for a variety of reasons, such as doing too much exercise, skipping a meal, or giving yourself too much insulin. 

Mild hypoglycemia (below 70 mg/dL) can often be treated by eating carbohydrates. In cases of severe hypoglycemia (below 54 mg/dL), a person may be unable or unwilling to swallow food or drinks to treat the low on their own. Glucagon can be administered in an emergency situation (when someone is unable or unwilling to consume carbohydrates, unresponsive, having a seizure, or in a coma) to quickly raise blood glucose levels.  

Guidelines for glucagon use

The American Diabetes Association (ADA’s) 2024 Standards of Care recommends that all people taking insulin or who are at high risk for hypoglycemia be prescribed glucagon, preferably ready-to-use glucagon products like Baqsimi, Gvoke, and Zegalogue. The Standards of Care also recommend that family members, caregivers, school employees and anyone else who cares for people with diabetes know where glucagon is located and how to use it. 

People with diabetes who use insulin or sulfonylureas are at the greatest risk of severe hypoglycemia. It’s a good idea for anyone with diabetes who uses insulin or sulfonylureas to have a prescription for glucagon. Ask your provider for a prescription if you don’t already have one. 

Research shows that glucagon is underprescribed and underused among both people with type 1 and type 2 diabetes, so the latest ADA guidelines mark an important step towards greater access to glucagon. 

Ready-to-use glucagon

Until 2019, traditional glucagon emergency kits were used to treat severe hypoglycemia. These kits required a multi-step reconstitution (mixing) process to turn powdered glucagon into a liquid that could be injected. 

In the stress of a severe hypoglycemic event, caregivers may become overwhelmed by the different steps of the preparation process. As a result, they may not be able to deliver the rescue glucagon correctly. These challenges contribute to the underuse of glucagon.

Ready-to-use emergency glucagons, or next-generation glucagons, were launched in 2019 with the approval of Gvoke HypoPen. These newer therapies offer greater convenience for people with diabetes and their caregivers, because they don’t require a complicated reconstitution process. Autoinjectors and nasal glucagon provide good options for children and others who may be afraid of needles. Lilly discontinued its traditional glucagon emergency kit at the end of 2022, though other companies like Novo Nordisk and Amphastar still offer traditional glucagon kits. 

List of ready-to-use glucagons

Common ready-to-use glucagon options include ready-to-use glucagon is available in two different forms: as an injection, or as a nasal powder.

• Autoinjectors: These glucagons are ready to inject (like an EpiPen for allergies) and are administered by a caregiver or trained individual, such as a family member or friend. 
  • Gvoke HypoPen is approved for people with diabetes ages 2 and up. Gvoke is also available as a pre-filled syringe, and GvokeKit offers a premixed vial and syringe. 
  • Zegalogue is approved for people with diabetes ages 6 and up. It is also available as a pre-filled syringe.  
• Nasal glucagon: This is a needle-free glucagon option. Since it does not require inhalation, it can be successfully administered by another person if the receiver is unconscious. 
  • Baqsimi is approved for people with diabetes ages 4 and up. It is currently the only nasal glucagon option. 

What's next for glucagon

Researchers are investigating microdosing, or using mini-doses of glucagon, to prevent hypoglycemia caused by exercise.

A small study found that using mini-dose glucagon, with or without reducing basal insulin delivery rate, can help reduce exercise-induced hypoglycemia in adults with type 1 diabetes. Although the study did not show differences in time in range, level 1 hypoglycemia (less than 70 mg/dL) was lower in people using mini-dose glucagon compared to those in the placebo group.

Glucagon is also being studied for use in automated insulin delivery (AID) systems. Beta Bionics, the company that makes the iLet AID system, is developing an AID system that delivers both insulin and glucagon to more precisely manage blood sugar.

This “dual hormone” system should eliminate the need to use carbs to manage low blood sugar – and early data has been promising. In a small study of teens, an investigational dual-hormone system led to similar time in range compared to an insulin-only system, with the exception of nighttime and exercise.

While more research is needed to fully understand these investigational uses, including the safety and efficacy of microdosing, and dual-hormone AID systems, it’s certainly an exciting time as researchers begin to better understand the multiple hormones involved in glycemic control.

Further reading about glucagon and hypoglycemia treatment

• Taking the Fear out of Low Blood Sugar: Next-Generation Glucagon
• Hypoglycemia Preparedness: How to Know Before You Go Low
• Expert Panel Shares Perspectives on Hypoglycemia

Photo credit: Susannah Chen