The T1D Exchange team has published an article in Current Diabetes Reports reviewing the current literature on glucagon usage and the emotional impact of severe hypoglycemia on people with type 1 diabetes (T1D) and the caregivers of people with T1D.

Through this review, we wanted to:

  1. Describe currently available rescue glucagon types, safety, efficacy, and preferences
  2. Review existing research regarding emergency glucagon usage, severe hypoglycemia, and the emotions associated with each

Read on for a summary of our findings:

Current Glucagons

Injectable Glucagon

While this injection has been shown to be a safe and effective way to treat severe hypoglycemia, this multi-step method of administration has some psychosocial barriers, as well as technical barriers.

There are currently two name brands of the glucagon emergency kit available:

  • Glucagon Emergency Kit from Eli Lilly and Co
  • GlucaGen Hypokit from Novo Nordisk

In December 2020, the FDA also approved a generic version of injectable glucagon in the U.S., which may make this rescue drug more widely available for people who cannot afford the name brands.

Nasal Glucagon

Nasal glucagon is absorbed through a person’s nose and starts working within 15 minutes.

Baqsimi (Eli Lilly and Co), was the first nasal glucagon approved by the FDA in 2019, although this type of glucagon has shown promise since the 1980s.

Caregivers reported that nasal glucagon was easy to administer and that they felt satisfied with using it, willing to carry it in their everyday lives, and found it less intimidating than injectable glucagon.

Importantly, studies show that there are typically fewer failures when nonmedical personnel use nasal glucagon than when they use injectable glucagon.

Autoinjector Glucagon

Doses of autoinjector glucagon are given as an injection under the skin, however, unlike the original injectable glucagon, the autoinjector glucagon pens are prefilled and ready to use. The liquid form of glucagon used in these devices is stable at room temperature and is just as effective as injectable glucagon.

There are currently two autoinjector glucagon pens available:

  • Gvoke HypoPen: Approved for adults and children at least 2 years old
  • Zegalogue Autoinjector: Approved for adults and children at least 6 years old

Studies have shown that the autoinjector is perceived by caregivers and people with T1D as easier to use, safer, and faster than the injectable glucagon.

Weighing Glucagon Options: Current Research on Preferences

While all of these glucagon types are effective and safe to use when administered properly, preference may be different among people who have T1D, their caregivers, and others who might have to administer glucagon in an emergency situation.

Injectable Glucagon vs. Nasal Glucagon

Utilizing injectable glucagon can be difficult to administer because it requires multiple steps, such as mixing powder and liquid, and it has to be administered immediately after mixing because it is not stable in liquid form.

In one study, caregivers and people unfamiliar with T1D care both preferred nasal glucagon over injectable glucagon and perceived it to be less complicated. Among the caregiver group, the number of successful administrations using nasal glucagon was significantly greater at almost 90% than the number of successful administrations using injectable glucagon at 26%.

Autoinjector Glucagon vs. Injectable Glucagon

While no published studies have directly assessed preferences between an FDA-approved autoinjector glucagon and the injectable glucagon, some studies suggest patients and caregivers prefer the autoinjector.

For example, in a recent study, the Dasiglucagon Hypopal autoinjector from Zealand Pharma had a higher rate of correct delivery than the injectable glucagon kit, it was preferred by 94% of participants, and all participants reported it as being easier and less stressful to use than injectable glucagon.

Nasal Glucagon vs. Autoinjector Glucagon

An interview study found that people with T1D, caregivers, and acquaintances of people with T1D preferred nasal glucagon over autoinjector glucagon. However, caregivers who were more familiar with needle injections were more likely to prefer the injectable glucagon kit over nasal glucagon.

A more recent online survey study found that people with T1D, caregivers, and acquaintances preferred nasal glucagon over autoinjector glucagon overall. Additionally, some people with T1D may prefer intramuscular glucagon for the potential to “mini” dose, which although not FDA-approved has shown promise in recent studies.

Hypoglycemia-Related Emotions and Experiences

In the last 25 years, researchers have been investigating the psychosocial impacts of hypoglycemia on a person with T1D’s emotional well-being and aspects of life such as sleep, work, and driving.

For people living with T1D:

Throughout several studies looking at the emotions around severe hypoglycemia, people with T1D reported experiencing:

  • Fear
  • Anxiety
  • Frustration
  • Confidence/self-efficacy
  • Hopefulness
  • Doubt
  • Motivation
  • Loneliness
  • Stress
  • Shame
  • Embarrassment

One interview study characterized the feeling of experiencing a severe hypoglycemic event as a time of intense emotion and panic for people with both type 1 and type 2 diabetes.

Severe hypoglycemia is a traumatic event and understanding people’s experiences can help develop interventions that will help alleviate negative emotions and increase preparedness for these events when they do occur.

For Caregivers:

Overall, parents generally report high levels of fear, depression, stress, and anxiety regarding severe hypoglycemia. Many studies have shown a negative relationship between parental quality of life (for example, sleep), with higher levels of reported fear of hypoglycemia.

In one of the largest studies in this area, mothers reported more preventative behaviors to avoid hypoglycemia after they had experienced a severe hypoglycemic episode with their child. This association was only found to be significant in mothers, but not in fathers. Another study also found that mothers of children with T1D had significantly higher levels of fear of hypoglycemia than fathers. However, there is no research that has investigated what may cause this difference.

The association between greater fear of hypoglycemia in parents and whether or not the child had experienced severe hypoglycemic events is unclear; some studies found a significant association while others did not.

Diabetes technologies have the potential to lower fear of hypoglycemia in both parents and children but will probably not eliminate it completely. Of note, one study found no difference in parental fear of hypoglycemia between parents whose children used CGMs and/or insulin pumps and those who did not.

Parents often reported grief and symptoms of depression at the time of their child’s diagnosis and resurgences of grief during times of illness and hospitalization. One study showed that parents with clinically significant depressive symptoms had higher reports of hypoglycemia worry when compared with parents without those depressive symptoms. Parents with depressive symptoms also consistently had higher levels of long-term diabetes distress.

Parents reported emotional burden regarding instructing others about diabetes, such as school personnel and family members. They also reported that worrying about their child’s short-term and long-term health consequences was a major burden.

Although caregivers’ emotions related to hypoglycemia have been studied extensively, there are few studies regarding caregivers’ emotions towards treatment options, including glucagon. Parents have generally reported that they feel anxious and intimidated by the traditional injectable glucagon. However, studies for the nasal and autoinjector glucagon have shown promise in eliminating those negative emotions.

More education is needed for people with T1D and caregivers about available glucagon options, when to give glucagon, and coping with living with diabetes. Additional studies and interventions are needed to reduce the negative emotions around hypoglycemia and glucagon usage.

For clinicians, tailored education should be delivered at the time of diagnosis and also throughout the years at clinic visits. It would also be valuable for glucagon makers to produce a simulation device for practicing at home. With the current wave of glucagon innovation, it is imperative that people with T1D and their families be kept up to date by their health care providers about new glucagon options as they come to market.

Read the full publication for “Emergency Glucagon: a Focused Review of Psychosocial Experiences of Rescue Drugs for Type 1 Diabetes”.