Beyond Insulin
Patients with Type 1 diabetes rely on insulin, but other medications are increasingly prescribed to help stabilize blood sugar levels, as well as secondary symptoms such as hypoglycemia. This journal scan will discuss the most recent literature on the efficacy and administration of supplemental treatments for Type 1 and 2 diabetes.
May 2021
Volume 10, Issue 2

Chapter 3: Emergency Glucagon Delivery for Hypoglycemia Treatment

Patients with diabetes should be taught to always have glucagon on hand.

2021;36:(3):149-154

In patients with diabetes, especially those who rely on insulin, a hypoglycemic event can happen anywhere and at any time. How to handle such an event and the use of emergency glucagon should be discussed with any family members, caretakers and other acquaintances such as coworkers who have regular interaction with the patient with diabetes.

Hypoglycemia typically occurs when blood glucose levels fall below 70 mg/dL (3.9 mM/L), but this is not a hard threshold, and it can also happen at levels above or below this average. Patients with “good” glycemic control (A1C levels <7%) are still susceptible to hypoglycemia. Furthermore, patients with Type 2 who are managing their disease with insulin are also at risk for hypoglycemia, especially those with a longer disease history as b-cell function continues to decrease with time.

As we accept that hypoglycemia can affect any diabetic, it is vital we know the signs of such an event and how to best treat it. At the Barbara Davis Center for Diabetes in Denver, Colorado, we regularly discuss the use of emergency glucagon with all of our Type 1 patients and their families. We train them on how to use emergency glycogen and when to treat severe hypoglycemic events. This happens during our new onset, day one education and then again at multiple time points moving forward. Having this mandatory training in hypoglycemic events is helpful because families of diabetic patients are universally concerned about insulin-associated hypoglycemia and the possibility of hypoglycemic seizures.

The American Diabetes Association (ADA), together with the European Association for the Study of Diabetes (EASD), has outlined three general levels of hypoglycemia from mild to severe that can help familiarize people with the characteristics of hypoglycemia.

Figure 1. Levels of Hypoglycemia outlined by the ADA and EASD

Table: Treatment for Hypoglycemia

Though mild hypoglycemia can be self-treated with oral glucose, it is sometimes difficult to know if a patient with diabetes is experiencing a mild hypoglycemic event or a more severe one requiring assistance. Carrying emergency glucagon becomes an important accessory to a diabetic’s daily life. Emergency glucagon comes in two forms, injectable or intranasal spray.

Injectable Glucagon

Injectable glucagon has been the standard of care in severe hypoglycemic events. In its most common rendition, it comes in a case containing a vial with 1mg lyophilized human synthetic glucagon and a syringe pre-filled with 1ml of sterile saline. The glucagon must be reconstituted before use. Ready-to-use glucagon in pre-filled syringes have recently become more available. A generic version was newly approved in December of 2020.

Once reconstituted, glucagon can be injected into multiple sites, most commonly the thighs, buttocks, or upper arm.  After injection, it can take up to 15 minutes before the diabetic regains consciousness. During this time, emergency personnel should be called. 

Nasal Glucagon

Intranasal glucagon for emergency use comes ready to use in a 3mg dosing spray bottle. The tip of the bottle is inserted into the nostril and sprayed. The powdered glucagon is designed to be absorbed in the mucosal lining of the nasal cavity. It does not need to reach the respiratory or olfactory mucosa. Thus, intranasal glucagon works even if the diabetic is unconscious or is experiencing nasal congestion. Early studies suggest that nasal glucagon is effective within 5 minutes of administration, but does not have the sustained effect seen with injectable glucagon. 

Both types of glucagon are equally effective in adults, adolescents and children. The primary differences lie in the perceptions of using one or the other. A recent article by Bajpai et al. researched how people felt about intranasal glucagon using an open-answer questionnaire given to diabetics, caregivers and other acquaintances who might need to administer emergency glucagon by injection or intranasal spray. 

Perceptions of injectable glucagon

Injectable glucagon was perceived by all study respondents as being more familiar. Of interest is that acquaintances, more so than patients and caregivers, commented that injectable glucose would be “harder to mess up” because it is easily recognized as an emergency medication delivery device, and it can be injected in multiple places. This gave them a sense of security when using the glucose injection method. 

Figure 2. Nasal cavity and the distribution of intranasal glucagon spray

Intranasal Hypoglycemia Treatment

Talking to patients about emergency glucagon

Though we regularly stress the importance of emergency glucagon, a recent study found that glucagon prescriptions were rarely filled, even among diabetics who had a previously severe hypoglycemic event. The percent of glucagon prescriptions filled in 2014 for emergency glucagon was less than 2% for Type 1 and less than 1% for Type 2 diabetic patients.

Why? Insurance coverage can be problem. Glucagon is sometimes not covered by insurance or has a high copay. 

Another factor is that the diabetic patient might fill their glucagon prescription at diagnosis, but then not use it or give it to their families, caregivers and acquaintances should they be unable to administer it themselves in a hypoglycemic emergency. This then attenuates the importance of it and they become negligent in carrying glucagon or filling their prescription refills. Clinicians can reinforce the significance of having a non-expired glucagon treatment at hand when we do follow-up appointments. We do not want any patients or families to be intimidated by the risk of hypoglycemia and then become tolerant to dangerously high blood sugar levels when glucagon can be administered precisely as needed instead.

Glucagon use as a treatment for hypoglycemia needs to be demystified. Clinicians should allow diabetic patients and their families to be honest about their thoughts and fears surrounding hypoglycemia and glucagon use. Demo materials can then help them create a plan on how they would prepare and use glucagon in an emergency situation so they feel prepared instead of afraid. Remind patients with diabetes and their families that they should always have one glucagon treatment at hand. Review and refresh patient and family training and education as time passes, particularly if they have not yet needed to use their glucagon.

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Chapter 4: Inhaled Insulin
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