Severe hypoglycemia (SH) is the most frequent and potentially serious complication affecting individuals with type 1 diabetes and can have major clinical and psychosocial consequences. Glucagon is the only approved treatment for SH that can be administered by non–health care professionals (HCPs); however, reports on the experiences and emotions of people with type 1 diabetes associated with SH and glucagon rescue use are limited. This survey study demonstrated that an increasing number of individuals with type 1 diabetes have current and filled prescriptions for glucagon and have been educated about glucagon rescue use by an HCP. Despite this positive trend, challenges with SH remain, including a high level of health care resource utilization, considerable out-of-pocket expenses for glucagon kits, a high prevalence of hypoglycemia unawareness, and a negative emotional impact on individuals with diabetes. Nocturnal and exercise-related hypoglycemia were concerns for most survey participants.

Insulin therapy carries an increased risk of hypoglycemia, a significant and potentially fatal complication of diabetes management (14). The American Diabetes Association (ADA) defines level 2 hypoglycemia as a blood glucose level <54 mg/dL (3.0 mmol/L). It is associated with impaired counterregulatory mechanisms that may lead to reduced awareness of hypoglycemic events, potentially leading to a cycle of recurrent hypoglycemia (3,4). Level 3 hypoglycemia (also called severe hypoglycemia [SH]) is defined by an altered mental and/or physical status that requires assistance from another person for recovery (3). In the United States, SH results in almost 300,000 emergency department visits per year (5). Untreated SH may lead to adverse clinical outcomes that can include cognitive dysfunction, loss of consciousness, seizures, coma, and death (2,3,6).

Long-term clinical studies have shown that SH remains an ongoing challenge for people with type 1 diabetes, occurring at an average rate of 0.36–0.41 episodes per person per year (7). A history of SH is a strong indicator for the risk of subsequent SH events (7), and people with type 1 diabetes are likely to experience several SH events in their lifetime. A clinical history of SH is associated with an increased risk of all-cause mortality and cardiovascular disease (CVD) in people with type 1 diabetes (8,9), which may lead to substantial direct and indirect costs (1012) and constitutes a significant part of the economic burden associated with diabetes (1316). Hypoglycemia can also significantly compromise a person’s emotional state and quality of life (2,3).

The potential negative impacts of SH are significant sources of distress for many individuals with type 1 diabetes and may create a strong aversion to situations in which SH might occur. This fear of hypoglycemia is prevalent among individuals with type 1 diabetes and may have substantial implications for diabetes management and subsequent health outcomes (3,17). Many people with diabetes who are worried about hypoglycemia maintain their blood glucose at higher than recommended levels to avoid the adverse effects of hypoglycemic episodes (18), thus contributing to the metabolic complications of hyperglycemia.

Glucagon has been the first-line emergency treatment for SH in insulin-treated people with diabetes since the 1960s (19). The ADA recommends prescribing glucagon for all individuals at an increased risk of level 2 and level 3 hypoglycemia so that it is available when needed (3). The ability to administer glucagon for the treatment of SH is not limited to health care professionals (HCPs); it can be administered by family members, caregivers, or bystanders (3). The significant burden of SH could be partially alleviated with the use of glucagon as recommended by the ADA (3). However, despite its favorable safety and efficacy profile, glucagon is underutilized as a rescue treatment for SH owing to a lack of routine prescribing of glucagon among HCPs, people with diabetes not filling their glucagon prescriptions, and caregivers not administering or not correctly administering glucagon in the event of SH (5,2023). First-generation glucagon kits (24,25) require reconstitution of lyophilized native human glucagon before use. The complexity of this multistep process is a known barrier to the rapid and efficient administration of glucagon (21,26,27). Other barriers include lack of appropriate education and training (21,22,26,27) and reluctance to administer rescue glucagon in an emergency for fear of harming the individual with SH (21,22,27).

Over many decades, there has been an unmet need for easy-to-use glucagon products to treat SH to aid in alleviating fear related to hypoglycemia, reduce training needs, and increase overall utilization of glucagon (27). Second-generation glucagon products do not require reconstitution and have been available on the U.S. market since 2019. These products include Baqsimi (Eli Lilly and Company) (28), a native human glucagon powder for nasal administration; Gvoke (Xeris Pharmaceuticals) (29), a ready-to-use premixed solution of native human glucagon for subcutaneous injection; and Zegalogue (Zealand Pharma) (30), a ready-to-use pre-mixed solution of the glucagon analog dasiglucagon for subcutaneous injection.

To date, there has been limited research on the experiences and emotions of individuals with diabetes regarding hypoglycemia and glucagon rescue use. This dearth of research is concerning considering the potentially severe consequences that a lack of glucagon use can have for SH recovery (19). To address these questions, we surveyed adults with type 1 diabetes to gain a real-world understanding of their experiences with hypoglycemia and the use of glucagon rescue products, identify barriers to glucagon use, and determine their preferences for glucagon rescue product characteristics. The objective of this study was to provide an updated real-world perspective on how the landscape of emergency glucagon use has changed since the introduction of second-generation, ready-to-use glucagon products in 2019.

Focus Groups Study to Inform Survey Development

The survey questions for this research were informed by focus groups conducted virtually from October to December 2020. In total, 38 adults with type 1 diabetes consented and participated. Seven focus groups with five to seven participants each were asked about their experiences with hypoglycemia and glucagon use. Participants were encouraged to interact with each other to gain robust insights. Each 90-minute session was recorded and transcribed for analysis. Each focus group participant was remunerated with a $100 Amazon gift card. The questions included in the survey for this study were developed from the key concepts that emerged during these focus groups.

Recruitment

Participants for the survey were recruited through the T1D Exchange registry (3133), a longitudinal study collecting information on type 1 diabetes management and outcomes. To be enrolled in the registry, individuals with type 1 diabetes must either receive insulin or have had a pancreas or islet cell transplant. In May 2021, recruitment emails were sent to the adult members of the T1D Exchange registry community, and posts were set up on social media (Facebook and Twitter) containing a link directing potential participants to a brief description of the research study.

Informed Consent

An institutional review board (IRB) exemption as well as a partial waiver of the Health Insurance Portability and Accountability Act authorization signature requirement for use and disclosure of protected health information were obtained from the WCG IRB on 22 April 2021. Potential study participants from the T1D Exchange registry community were provided with a link to an electronic consent form for their review and electronic signature. Participants who provided consent were then emailed a copy of their informed consent form for their records.

Inclusion Criteria

Participants enrolled in the study were included in the data analysis if they satisfied the following criteria: ≥18 years of age, diagnosis of type 1 diabetes for at least 1 year, at least one episode of SH defined as a low blood glucose event during which assistance was required, familiarity with current glucagon options on the market, currently residing in the United States, fluent in written and spoken English, and agreed to provide digital informed consent. Participants were excluded from the analysis if they were currently pregnant or refused to declare whether they were pregnant.

Survey

Consenting participants were directed to the online survey conducted via Alchemer (34). After completing the survey, each participant was remunerated with a $25 Amazon gift card. For the purposes of the survey, participants’ experiences with hypoglycemia were classified as “mild” (blood glucose <70 mg/dL [3.9 mmol/L] to ≥54 mg/dL [3.0 mmol/L]), “moderate” (blood glucose <54 mg/dL [3.0 mmol/L]), and “severe” (an altered mental and/or physical status requiring assistance for treatment of hypoglycemia). Definitions of these classifications were provided to participants as they completed the survey. Some survey questions allowed for multiple answers to be given, resulting in an overall percentage in excess of 100%. These questions are noted in the results tables.

Statistical Analysis

All statistical analyses were performed using R software, v. 4.0.5 or later (R Core Team, Vienna, Austria). Summary statistics, including mean, SD, frequency, and percentage, were calculated for general demographic and diabetes-related health information. Bivariate statistical analyses were performed using Welch two-sample t tests, Pearson χ2 tests, and Fisher exact tests to assess differences in demographic and clinical characteristics between participants who, at the time of the survey, had a current and filled glucagon prescription and those who did not and between participants who had impaired awareness of hypoglycemia and those who did not. A P value ≤0.05 was considered statistically significant.

Participants’ Demographics and Clinical Characteristics

In total, 428 individuals consented and were enrolled in the study. Of these, 316 individuals met the inclusion criteria and completed the survey. The baseline participant characteristics are shown in Table 1.

TABLE 1

Participants’ Demographics (N = 316)

CharacteristicValue
Age, years 35.6 ± 8.9 
Duration of type 1 diabetes, years 17.2 ± 12.7 
Gender
 Female
 Male
 Other 

187 (59.2)
128 (40.5)
1 (0.3) 
Race (multiple answers possible)
 White
 Black or African American
 Asian
 American Indian or Alaskan Native
 Native Hawaiian or other Pacific Islander
 Other 

290 (91.8)
12 (3.8)
9 (2.8)
8 (2.5)
1 (0.3)
4 (1.3) 
Ethnicity
 Not Hispanic or Latino
 Hispanic or Latino 

302 (95.6)
14 (4.4) 
Employment status (multiple answers possible)
 Working full time
 Working part time
 Student
 Temporarily unemployed or on leave from work
 Unemployed, looking for work
 Volunteer
 Disabled
 Unemployed, not looking for work
 Retired 

195 (61.7)
65 (20.6)
36 (11.4)
13 (4.1)
12 (3.8)
9 (2.8)
8 (2.5)
6 (1.9)
2 (0.6) 
Health insurance (multiple answers possible)
 Private health insurance (e.g., commercial, fee-for-service, HMO, PPO, or POS)
 Medicare
 Medicaid
 Other government-sponsored health coverage plan
 Affordable Care Act plan
 Medigap
 Single service plan (e.g., dental, vision, or prescriptions)
 Military health care (e.g., TRICARE, CHAMPUS, CHAMPVA, or VA)
 Other state-sponsored health coverage plan
 No health insurance or health care coverage of any type
 Not known 

187 (59.2)

71 (22.5)
34 (10.8)
12 (3.8)
8 (2.5)
7 (2.2)
6 (1.9)

6 (1.9)

5 (1.6)
4 (1.3)

1 (0.3) 
Education
 Bachelor’s degree
 Some college
 Master’s degree
 Associate’s degree
 Doctoral degree
 High school graduate/GED
 Some high school 

111 (35.1)
77 (24.4)
57 (18.0)
33 (10.4)
14 (4.4)
12 (3.8)
12 (3.8) 
Annual household income
 <$30,000
 $30,000 to <$50,000
 $50,000 to <$75,000
 $75,000 to <$100,000
 $100,000 to <$200,000
 ≥$200,000
 Do not wish to provide
 Not known 

44 (13.9)
41 (13.0)
85 (26.9)
53 (16.8)
54 (17.1)
18 (5.7)
12 (3.8)
9 (2.8) 
CharacteristicValue
Age, years 35.6 ± 8.9 
Duration of type 1 diabetes, years 17.2 ± 12.7 
Gender
 Female
 Male
 Other 

187 (59.2)
128 (40.5)
1 (0.3) 
Race (multiple answers possible)
 White
 Black or African American
 Asian
 American Indian or Alaskan Native
 Native Hawaiian or other Pacific Islander
 Other 

290 (91.8)
12 (3.8)
9 (2.8)
8 (2.5)
1 (0.3)
4 (1.3) 
Ethnicity
 Not Hispanic or Latino
 Hispanic or Latino 

302 (95.6)
14 (4.4) 
Employment status (multiple answers possible)
 Working full time
 Working part time
 Student
 Temporarily unemployed or on leave from work
 Unemployed, looking for work
 Volunteer
 Disabled
 Unemployed, not looking for work
 Retired 

195 (61.7)
65 (20.6)
36 (11.4)
13 (4.1)
12 (3.8)
9 (2.8)
8 (2.5)
6 (1.9)
2 (0.6) 
Health insurance (multiple answers possible)
 Private health insurance (e.g., commercial, fee-for-service, HMO, PPO, or POS)
 Medicare
 Medicaid
 Other government-sponsored health coverage plan
 Affordable Care Act plan
 Medigap
 Single service plan (e.g., dental, vision, or prescriptions)
 Military health care (e.g., TRICARE, CHAMPUS, CHAMPVA, or VA)
 Other state-sponsored health coverage plan
 No health insurance or health care coverage of any type
 Not known 

187 (59.2)

71 (22.5)
34 (10.8)
12 (3.8)
8 (2.5)
7 (2.2)
6 (1.9)

6 (1.9)

5 (1.6)
4 (1.3)

1 (0.3) 
Education
 Bachelor’s degree
 Some college
 Master’s degree
 Associate’s degree
 Doctoral degree
 High school graduate/GED
 Some high school 

111 (35.1)
77 (24.4)
57 (18.0)
33 (10.4)
14 (4.4)
12 (3.8)
12 (3.8) 
Annual household income
 <$30,000
 $30,000 to <$50,000
 $50,000 to <$75,000
 $75,000 to <$100,000
 $100,000 to <$200,000
 ≥$200,000
 Do not wish to provide
 Not known 

44 (13.9)
41 (13.0)
85 (26.9)
53 (16.8)
54 (17.1)
18 (5.7)
12 (3.8)
9 (2.8) 

Data are mean ± SD or n (%). CHAMPUS, Civilian Health and Medical Program of the Uniformed Services; CHAMPVA, Civilian Health and Medical Program of the Department of Veterans Affairs; GED, general education diploma; HMO, health maintenance organization; POS, point of service; PPO, preferred provider organization; VA, Veterans Affairs.

Participants had a mean ± SD age of 35.6 ± 8.9 years and a mean duration of type 1 diabetes of 17.2 ± 12.7 years since their diagnosis. Of the participants, 59.2% were female, most were White and identified as not Hispanic or Latino, and the majority were in full-time or part-time employment. Overall, 59.2% had private health insurance; 22.5% and 10.8% were enrolled in Medicare or Medicaid, respectively; 1.3% did not have health insurance of any type; and the remainder received health insurance from other sources. In terms of education, 57.5% reported having a bachelor’s degree or higher, and 66.5% had an annual household income ≥$50,000.

The clinical characteristics of participants are summarized in Table 2. The most frequently used method of glucose monitoring was real-time continuous glucose monitoring (CGM; 80.4%), followed by traditional fingerstick blood glucose monitoring (BGM; 47.2%) and intermittently scanning CGM, formerly called flash CGM (FGM; 0.9%). Most participants (76.6%) reported using an insulin pump, 30.4% used injectable insulin, and 4.1% used inhalable insulin. Participants reported comorbid conditions, the most frequent of which were joint issues (27.5%), hypothyroidism (25.3%), CVD (19.3%), and retinopathy (19.3%). Overall, 69.3% were seen by an adult or pediatric endocrinologist, and 22.8% were seen by other specialized diabetes HCPs, with the remainder seen by primary care HCPs.

TABLE 2

Participants’ Clinical Characteristics (N = 316)

CharacteristicValue
Glucose monitoring method (multiple answers possible)
 CGM
 BGM
 FGM 

254 (80.4)
149 (47.2)
3 (0.9) 
Duration of CGM use (n = 254)
 <6 months
 6 months to <1 year
 1 year to <3 years
 3 years to <5 years
 ≥5 years 

10 (3.9)
20 (7.9)
105 (41.3)
49 (19.3)
70 (27.6) 
Blood glucose tests
 A1C, %
 Number of daily fingerstick blood glucose checks
 Number of daily glucose checks by CGM/FGM 

7.4 ± 2.5
2.4 ± 2.6
20.7 ± 25 
Insulin delivery method (multiple answers possible)
 Insulin pump
 Multiple daily injections using an insulin pen
 Multiple daily injections using vial/syringe
 Inhalable insulin
 Other 

242 (76.6)
59 (18.7)
37 (11.7)
13 (4.1)
1 (0.3) 
Reported diabetes-related comorbidities (multiple answers possible)
 Joint issues
 Hypothyroidism
 Retinopathy
 CVD
 Gastroparesis
 Neuropathy
 Sexual dysfunction
 Nephropathy
 Hyperthyroidism 


87 (27.5)
80 (25.3)
61 (19.3)
61 (19.3)
51 (16.1)
46 (14.6)
44 (13.9)
22 (7.0)
18 (5.7) 
Type of diabetes HCP
 Adult endocrinologist
 Diabetes nurse practitioner
 Diabetes physician assistant
 Pediatric endocrinologist
 Primary care physician
 Primary care, nurse practitioner
 Primary care, physician assistant 

203 (64.2)
48 (15.2)
24 (7.6)
16 (5.1)
14 (4.4)
7 (2.2)
4 (1.3) 
Frequency of visits with diabetes HCP
 Every month
 Every 2–3 months
 Every 6 months
 Once per year
 Once every 1–2 years
 Other 

9 (2.8)
201 (63.6)
92 (29.1)
6 (1.9)
2 (0.6)
6 (1.9) 
CharacteristicValue
Glucose monitoring method (multiple answers possible)
 CGM
 BGM
 FGM 

254 (80.4)
149 (47.2)
3 (0.9) 
Duration of CGM use (n = 254)
 <6 months
 6 months to <1 year
 1 year to <3 years
 3 years to <5 years
 ≥5 years 

10 (3.9)
20 (7.9)
105 (41.3)
49 (19.3)
70 (27.6) 
Blood glucose tests
 A1C, %
 Number of daily fingerstick blood glucose checks
 Number of daily glucose checks by CGM/FGM 

7.4 ± 2.5
2.4 ± 2.6
20.7 ± 25 
Insulin delivery method (multiple answers possible)
 Insulin pump
 Multiple daily injections using an insulin pen
 Multiple daily injections using vial/syringe
 Inhalable insulin
 Other 

242 (76.6)
59 (18.7)
37 (11.7)
13 (4.1)
1 (0.3) 
Reported diabetes-related comorbidities (multiple answers possible)
 Joint issues
 Hypothyroidism
 Retinopathy
 CVD
 Gastroparesis
 Neuropathy
 Sexual dysfunction
 Nephropathy
 Hyperthyroidism 


87 (27.5)
80 (25.3)
61 (19.3)
61 (19.3)
51 (16.1)
46 (14.6)
44 (13.9)
22 (7.0)
18 (5.7) 
Type of diabetes HCP
 Adult endocrinologist
 Diabetes nurse practitioner
 Diabetes physician assistant
 Pediatric endocrinologist
 Primary care physician
 Primary care, nurse practitioner
 Primary care, physician assistant 

203 (64.2)
48 (15.2)
24 (7.6)
16 (5.1)
14 (4.4)
7 (2.2)
4 (1.3) 
Frequency of visits with diabetes HCP
 Every month
 Every 2–3 months
 Every 6 months
 Once per year
 Once every 1–2 years
 Other 

9 (2.8)
201 (63.6)
92 (29.1)
6 (1.9)
2 (0.6)
6 (1.9) 

Data are n (%) or mean ± SD.

Participants’ Experiences With Hypoglycemia

Participants’ reported experiences with hypoglycemia are presented in Table 3. Participants disclosed experiencing a mean of 3.6 ± 6.0 SH events in the preceding 12 months and a mean of 15.3 ± 60.4 (median 5, range 1–1,000) SH events in total in their lifetime. Participants noticed hypoglycemia in a variety of ways, most commonly by experiencing symptoms (80.7%), but also by using the functions of their CGM system (alert [63.3%], glucose reading [49.7%], or predictive low glucose warning [48.1%]). About one-fourth of the participants also made use of fingerstick BGM.

TABLE 3

Participants’ Experiences With Hypoglycemia (N = 316)

Hypoglycemia-Related Survey DataValue
Hypoglycemia data
 Blood glucose level at which hypoglycemia is being treated, mg/dL
 Number of mild hypoglycemic events per week
 Number of moderate hypoglycemic events per week
 Number of SH events in the previous 12 months
 Number of SH events in the lifetime 

70.2 ± 21.8

7.4 ± 13.2
5.0 ± 13.3
3.6 ± 6.0
15.3 ± 60.4 
How hypoglycemia is usually noticed (multiple answers possible)
 Feeling symptoms
 CGM low alert
 Looking at the CGM reading
 CGM predictive low glucose warning
 Fingerstick BGM
 Other 


255 (80.7)
200 (63.3)
157 (49.7)
152 (48.1)
82 (25.9)
5 (1.6) 
Number of SH events
 In the previous 12 months
  CGM users (n = 254)
  Non-CGM users (n = 62)
 In the lifetime
  CGM users (n = 254)
  Non-CGM users (n = 62)
 In the lifetime, excluding those with >100 lifetime events (n = 3)
  CGM users (n = 251)
  Non-CGM users (n = 62) 


3.1 ± 4.2
5.7 ± 10.6

15.9 ± 66.5
13.2 ± 21.7


10.4 ± 16.7
13.2 ± 21.7 
Awareness of hypoglycemia
 1 (always aware)
 2
 3
 4
 5
 6
 7 (never aware) 

30 (9.5)
77 (24.4)
68 (21.5)
85 (26.9)
43 (13.6)
7 (2.2)
6 (1.9) 
Times that hypoglycemia is of most concern (multiple answers possible)
 Overnight
 During exercise
 After exercise
 During the day
 Other 


238 (75.3)
139 (44.0)
105 (33.2)
87 (27.5)
17 (5.4) 
Occurrence of the most recent SH event
 <1 month ago
 1–3 months ago
 3 months to <6 months ago
 6 months to 1 year ago
 1–2 years ago
 2–5 years ago
 >5 years ago 

44 (13.9)
76 (24.1)
51 (16.1)
48 (15.2)
30 (9.5)
22 (7.0)
45 (14.2) 
Type of emergency resulting from SH (multiple answers possible)
 Change in mental state requiring assistance
 Passing out/loss of consciousness or seizure
 Calling a paramedic
 Emergency department visit(s)
 Requiring glucagon
 Hospitalizations with at least 1 night spent in the hospital 



258 (81.6)
196 (62.0)
195 (61.7)
185 (58.5)
181 (57.3)
115 (36.4) 
Emotions experienced in connection with SH (multiple answers possible)
 Worry/concern
 Anxiety
 Stress
 Fear
 Panic
 Weakness
 Embarrassment
 Anger
 Guilt
 Sadness
 Shame 


214 (67.7)
203 (64.2)
202 (63.9)
172 (54.4)
166 (52.5)
159 (50.3)
160 (50.6)
112 (35.4)
106 (33.5)
89 (28.2)
67 (21.2) 
Hypoglycemia-Related Survey DataValue
Hypoglycemia data
 Blood glucose level at which hypoglycemia is being treated, mg/dL
 Number of mild hypoglycemic events per week
 Number of moderate hypoglycemic events per week
 Number of SH events in the previous 12 months
 Number of SH events in the lifetime 

70.2 ± 21.8

7.4 ± 13.2
5.0 ± 13.3
3.6 ± 6.0
15.3 ± 60.4 
How hypoglycemia is usually noticed (multiple answers possible)
 Feeling symptoms
 CGM low alert
 Looking at the CGM reading
 CGM predictive low glucose warning
 Fingerstick BGM
 Other 


255 (80.7)
200 (63.3)
157 (49.7)
152 (48.1)
82 (25.9)
5 (1.6) 
Number of SH events
 In the previous 12 months
  CGM users (n = 254)
  Non-CGM users (n = 62)
 In the lifetime
  CGM users (n = 254)
  Non-CGM users (n = 62)
 In the lifetime, excluding those with >100 lifetime events (n = 3)
  CGM users (n = 251)
  Non-CGM users (n = 62) 


3.1 ± 4.2
5.7 ± 10.6

15.9 ± 66.5
13.2 ± 21.7


10.4 ± 16.7
13.2 ± 21.7 
Awareness of hypoglycemia
 1 (always aware)
 2
 3
 4
 5
 6
 7 (never aware) 

30 (9.5)
77 (24.4)
68 (21.5)
85 (26.9)
43 (13.6)
7 (2.2)
6 (1.9) 
Times that hypoglycemia is of most concern (multiple answers possible)
 Overnight
 During exercise
 After exercise
 During the day
 Other 


238 (75.3)
139 (44.0)
105 (33.2)
87 (27.5)
17 (5.4) 
Occurrence of the most recent SH event
 <1 month ago
 1–3 months ago
 3 months to <6 months ago
 6 months to 1 year ago
 1–2 years ago
 2–5 years ago
 >5 years ago 

44 (13.9)
76 (24.1)
51 (16.1)
48 (15.2)
30 (9.5)
22 (7.0)
45 (14.2) 
Type of emergency resulting from SH (multiple answers possible)
 Change in mental state requiring assistance
 Passing out/loss of consciousness or seizure
 Calling a paramedic
 Emergency department visit(s)
 Requiring glucagon
 Hospitalizations with at least 1 night spent in the hospital 



258 (81.6)
196 (62.0)
195 (61.7)
185 (58.5)
181 (57.3)
115 (36.4) 
Emotions experienced in connection with SH (multiple answers possible)
 Worry/concern
 Anxiety
 Stress
 Fear
 Panic
 Weakness
 Embarrassment
 Anger
 Guilt
 Sadness
 Shame 


214 (67.7)
203 (64.2)
202 (63.9)
172 (54.4)
166 (52.5)
159 (50.3)
160 (50.6)
112 (35.4)
106 (33.5)
89 (28.2)
67 (21.2) 

Data are mean ± SD or n (%).

When comparing SH events in the previous 12 months for participants who used or did not use CGM, CGM users experienced a mean of 3.1 ± 4.2 (median 1.0, range 0–30) SH events, and non-CGM users experienced a mean of 5.7 ± 10.6 (median 2.5, range 0–58) SH events. Excluding participants who reported having had >100 lifetime SH events (n = 3), CGM users reported a mean of 10.4 ± 17.7 (median 5.0, range 1–100) SH events in their lifetime, and non-CGM users reported a mean of 13.2 ± 21.7 (median 4.5, range 0–100) SH events in their lifetime.

Using the criteria employed by Gold et al. (35), participants’ awareness of hypoglycemia was classified as “normal” (scores of 1–2) or “impaired” (scores of 4–7) on a visual analog scale. “Indeterminant” awareness (score of 3) was not included in either of these categories. Overall, 33.9% of the participants reported having normal awareness of hypoglycemia, and 44.6% reported having impaired awareness of hypoglycemia. Most participants (75.3%) considered the night or the time during or after exercise (77.2%) as the time of most concern about hypoglycemia.

SH events were associated with several emergency situations, including calling an ambulance (61.7%), visiting an emergency department (58.5%), and staying for at least 1 night at the hospital (36.4%). More than half of the participants stated that they had felt either worry, anxiety, stress, fear, panic, weakness, or embarrassment during an SH episode.

Participants’ Experiences With Glucagon Rescue Treatments

Participants’ experiences with glucagon rescue treatments are reported in Table 4. Almost all participants (97.2%) had been prescribed glucagon either at the time of completing the survey or in the past, with 80.4% reporting a current glucagon prescription. Overall, 74.7% of participants had a current and filled glucagon prescription, and 25.3% did not. Participants reported a mean of 1.7 ± 5.3 uses of glucagon to treat SH in the previous 12 months.

TABLE 4

Participants’ Experiences With Glucagon Rescue Treatments (N = 316)

Glucagon-Related Survey DataValue
Current prescription for glucagon
 Yes, currently have a glucagon prescription and have filled it
 Yes, have been prescribed glucagon in the past but not recently
 Yes, currently have a glucagon prescription but have not filled it
 No, have never had a glucagon prescription 

236 (74.7)

53 (16.8)

18 (5.7)

9 (2.8) 
Number of times glucagon was used to treat SH in the previous 12 months 1.7 ± 5.3 
Likelihood of having a current and filled glucagon prescription
 Impaired awareness of hypoglycemia (scores 4–7; n = 141)
  Having a current and filled glucagon prescription
  Not having a current and filled glucagon prescription
 Not having impaired awareness of hypoglycemia (scores 1–3; n = 175)
  Having a current and filled glucagon prescription
  Not having a current and filled glucagon prescription 




113 (80.1)
28 (19.9)


123 (70.3)
52 (29.7) 
Current ownership of a glucagon kit
 Yes
 No
 Unsure 

251 (79.4)
62 (19.6)
3 (0.9) 
Age of glucagon kit if currently owning one (n = 251)
 <1 year old
 1–2 years old
 >2 years old 

114 (45.4)
117 (46.6)
20 (8.0) 
Feelings associated with having a glucagon kit at home (n = 316; multiple answers possible)
 Safe
 Prepared for hypoglycemia
 Confident about hypoglycemia
 The same as not having it in my home 


151 (47.8)
127 (40.2)
90 (28.5)
87 (27.5) 
Educated by an HCP about glucagon use
 Yes
 No
 Unsure 

263 (83.2)
47 (14.9)
6 (1.9) 
Glucagon-Related Survey DataValue
Current prescription for glucagon
 Yes, currently have a glucagon prescription and have filled it
 Yes, have been prescribed glucagon in the past but not recently
 Yes, currently have a glucagon prescription but have not filled it
 No, have never had a glucagon prescription 

236 (74.7)

53 (16.8)

18 (5.7)

9 (2.8) 
Number of times glucagon was used to treat SH in the previous 12 months 1.7 ± 5.3 
Likelihood of having a current and filled glucagon prescription
 Impaired awareness of hypoglycemia (scores 4–7; n = 141)
  Having a current and filled glucagon prescription
  Not having a current and filled glucagon prescription
 Not having impaired awareness of hypoglycemia (scores 1–3; n = 175)
  Having a current and filled glucagon prescription
  Not having a current and filled glucagon prescription 




113 (80.1)
28 (19.9)


123 (70.3)
52 (29.7) 
Current ownership of a glucagon kit
 Yes
 No
 Unsure 

251 (79.4)
62 (19.6)
3 (0.9) 
Age of glucagon kit if currently owning one (n = 251)
 <1 year old
 1–2 years old
 >2 years old 

114 (45.4)
117 (46.6)
20 (8.0) 
Feelings associated with having a glucagon kit at home (n = 316; multiple answers possible)
 Safe
 Prepared for hypoglycemia
 Confident about hypoglycemia
 The same as not having it in my home 


151 (47.8)
127 (40.2)
90 (28.5)
87 (27.5) 
Educated by an HCP about glucagon use
 Yes
 No
 Unsure 

263 (83.2)
47 (14.9)
6 (1.9) 

Data are n (%) or mean ± SD.

Participants who had impaired awareness of hypoglycemia (scores 4–7, n = 141) were significantly more likely to have a current and filled glucagon prescription than those who did not have impaired awareness of hypoglycemia (scores 1–3, n = 175): 80.1% (113 of 141) versus 70.3% (123 of 175) (Pearson χ2 test P = 0.05). There were no significant differences between those with or without a current and filled glucagon prescription in A1C (P = 0.31) or age (P = 0.19). In addition, having a current and filled glucagon prescription was not associated with a greater likelihood of receiving care from an endocrinologist (P = 0.70).

Overall, 79.4% of the participants (n = 251) reported that they currently owned a glucagon kit, with 92.0% (n = 231) owning a kit <2 years old and 8.0% (n = 20) owning a kit >2 years old. Approximately half of the participants stated that having a glucagon kit in their home made them feel safe, 40.2% felt that they were prepared for hypoglycemia, and 28.5% felt confident about hypoglycemia; however, 27.5% reported that having a glucagon kit in their home made no difference in how they felt about hypoglycemia. HCPs had provided education about glucagon use to 83.2% of the participants, but 16.8% of participants had not received education by an HCP or were unsure about whether they had received such education. Compared with other HCPs, care from an endocrinologist was not associated with better education about glucagon use (P = 0.60).

Barriers to Glucagon Use as a Rescue Treatment

Barriers to glucagon rescue use reported by the participants are included in Table 5. Importantly, the 251 participants who currently owned a glucagon kit had a mean out-of-pocket cost of $73.40 ± $85.80 (median $30, range $0–400) for their kit. When queried, 85.1% of the 316 participants reported that rescue glucagon was administered when needed. In the remaining 14.9% (n = 47) for whom glucagon was not administered when needed, the reasons were diverse, including problems with the reconstitution and administration process (n = 33), inability to locate the kit (n = 23), lack of training (n = 15), an expired kit (n = 14), the rescuing individual being unaware of the existence of the kit (n = 13), and lack of confidence of the rescuing individual (n = 7).

TABLE 5

Barriers to Using Glucagon Rescue Treatment

Barrier-Related Survey DataValue
Out-of-pocket cost for a glucagon kit, $ (n = 251) 73.40 (85.80) 
Ability to have available glucagon administered (n = 316)
 Able
 Unable 

269 (85.1)
47 (14.9) 
Reasons for inability to have available glucagon administered (n = 47; multiple answers possible)
 The rescuing individual was not able to locate the glucagon kit.
 The rescuing individual was not trained to use the glucagon kit.
 The glucagon was expired.
 The rescuing individual was not aware of the glucagon kit.
 There was a problem with mixing.
 The rescuing individual was not able to use the glucagon kit correctly.
 The rescuing individual was not comfortable administering the glucagon.
 The rescuing individual who delivered glucagon broke the needle.
 The process was too complex.
 Other 

23 (48.9)
15 (31.9)
14 (29.8)
13 (27.7)
11 (23.4)
10 (21.3)
7 (14.9)
7 (14.9)
5 (10.6)
3 (6.4) 
Reasons for not currently having a glucagon prescription (n = 9; multiple answers possible)
 My doctor has never discussed glucagon with me.
 I carry other supplies instead (glucose tablets, juice, etc.).
 My CGM device gives me alerts before my blood glucose gets too low.
 I don’t need it.
 I am worried about temperature changes affecting the kit.
 It costs too much to fill the prescription.
 The kit has too many steps to be useful.
 There is nobody to administer the glucagon (e.g., living alone).
 Those around me would call 911 if I became severely hypoglycemic.
 Other 

6 (66.7)
6 (66.7)
5 (55.6)
1 (11.1)
1 (11.1)
1 (11.1)
1 (11.1)
1 (11.1)
1 (11.1)
1 (11.1) 
Barrier-Related Survey DataValue
Out-of-pocket cost for a glucagon kit, $ (n = 251) 73.40 (85.80) 
Ability to have available glucagon administered (n = 316)
 Able
 Unable 

269 (85.1)
47 (14.9) 
Reasons for inability to have available glucagon administered (n = 47; multiple answers possible)
 The rescuing individual was not able to locate the glucagon kit.
 The rescuing individual was not trained to use the glucagon kit.
 The glucagon was expired.
 The rescuing individual was not aware of the glucagon kit.
 There was a problem with mixing.
 The rescuing individual was not able to use the glucagon kit correctly.
 The rescuing individual was not comfortable administering the glucagon.
 The rescuing individual who delivered glucagon broke the needle.
 The process was too complex.
 Other 

23 (48.9)
15 (31.9)
14 (29.8)
13 (27.7)
11 (23.4)
10 (21.3)
7 (14.9)
7 (14.9)
5 (10.6)
3 (6.4) 
Reasons for not currently having a glucagon prescription (n = 9; multiple answers possible)
 My doctor has never discussed glucagon with me.
 I carry other supplies instead (glucose tablets, juice, etc.).
 My CGM device gives me alerts before my blood glucose gets too low.
 I don’t need it.
 I am worried about temperature changes affecting the kit.
 It costs too much to fill the prescription.
 The kit has too many steps to be useful.
 There is nobody to administer the glucagon (e.g., living alone).
 Those around me would call 911 if I became severely hypoglycemic.
 Other 

6 (66.7)
6 (66.7)
5 (55.6)
1 (11.1)
1 (11.1)
1 (11.1)
1 (11.1)
1 (11.1)
1 (11.1)
1 (11.1) 

Data are n (%).

The most important reasons for not having a glucagon prescription stated by participants who have never been prescribed glucagon (n = 9) were that their doctor had never discussed it with them (n = 6), they usually carried oral carbohydrates (n = 6), and their CGM device alerted them to low blood glucose levels (n = 5).

Participants’ Preferences for Characteristics of Glucagon Rescue Products

Most participants preferred ready-to-use glucagon rescue products, with 47.8% favoring an intranasal spray and 38.0% a premixed autoinjector (Table 6). The remaining 14.2% of the participants preferred injectable glucagon that requires reconstitution before use. Valued characteristics of glucagon rescue treatments included the ease of use of ready-to-use products (76.3%), intuitive modes of administration such as a nasal spray or ready-to-use injection (55.7%), a fast onset of action (53.5%), and storage at room temperature (42.1%).

TABLE 6

Participants’ Preferences for Characteristics of Glucagon Products (N = 316)

Preference-Related Survey DataValue
Preferred method of glucagon administration
 Intranasal—spray in the nose
 Premixed autoinjector—already reconstituted
 Injection—needs to be reconstituted 

151 (47.8)
120 (38.0)
45 (14.2) 
Preferred characteristics of glucagon rescue treatments (multiple answers possible)
 Ease of use (ready-to-use treatment)
 The way it is administered (nasal spray, ready-to-use injection)
 How fast the glucagon works compared with others on the market
 Treatment that can be carried at room temperature (vs. stored in a refrigerator)
 Having multiple kits available 


241 (76.3)
176 (55.7)

169 (53.5)

133 (42.1)

102 (32.3) 
Main improvements to be made in glucagon rescue treatments (multiple answers possible)
 Ease of use (premixed dosing)
 Cost
 Administration type (nasal, syringe)
 Storage options
 Time to physical recovery
 Fewer steps in the instructions
 Size of kit
 All of the above
 Other 


198 (62.7)
169 (53.5)
159 (50.3)
122 (38.6)
126 (39.9)
96 (30.4)
99 (31.3)
39 (12.3)
3 (0.9) 
Importance of time to plasma glucose recovery in glucagon rescue treatments
 Very important
 Fairly important
 Important
 Slightly important
 Not at all important 


148 (46.8)
84 (26.6)
57 (18.0)
26 (8.2)
1 (0.3) 
Preference-Related Survey DataValue
Preferred method of glucagon administration
 Intranasal—spray in the nose
 Premixed autoinjector—already reconstituted
 Injection—needs to be reconstituted 

151 (47.8)
120 (38.0)
45 (14.2) 
Preferred characteristics of glucagon rescue treatments (multiple answers possible)
 Ease of use (ready-to-use treatment)
 The way it is administered (nasal spray, ready-to-use injection)
 How fast the glucagon works compared with others on the market
 Treatment that can be carried at room temperature (vs. stored in a refrigerator)
 Having multiple kits available 


241 (76.3)
176 (55.7)

169 (53.5)

133 (42.1)

102 (32.3) 
Main improvements to be made in glucagon rescue treatments (multiple answers possible)
 Ease of use (premixed dosing)
 Cost
 Administration type (nasal, syringe)
 Storage options
 Time to physical recovery
 Fewer steps in the instructions
 Size of kit
 All of the above
 Other 


198 (62.7)
169 (53.5)
159 (50.3)
122 (38.6)
126 (39.9)
96 (30.4)
99 (31.3)
39 (12.3)
3 (0.9) 
Importance of time to plasma glucose recovery in glucagon rescue treatments
 Very important
 Fairly important
 Important
 Slightly important
 Not at all important 


148 (46.8)
84 (26.6)
57 (18.0)
26 (8.2)
1 (0.3) 

Data are n (%).

The participants also discussed various ways to improve glucagon rescue products, including greater ease of use (62.7%), reduced cost (53.5%), and more intuitive modes of administration (50.3%). The time to plasma glucose recovery was rated as a “very important” or “fairly important” characteristic of glucagon rescue products by 73.4% of the participants (Table 6).

The burden of SH remains a challenge throughout the lives of people with type 1 diabetes and has a substantial impact on their emotional well-being, diabetes management, and health outcomes (17,27). Although previous studies have examined the emotional impact of SH and glucagon rescue treatment on caregivers of individuals with type 1 diabetes (3638), literature is limited about the views and emotions connected with hypoglycemia and glucagon rescue use of people with type 1 diabetes themselves (19). For this reason, the objective of this research study was to provide an updated real-world perspective on emergency glucagon use of individuals with type 1 diabetes, as available glucagon products have become more diversified with the introduction of second-generation, ready-to-use rescue products.

The surveyed sample of individuals with type 1 diabetes had a mean age of 35.6 ± 8.9 years and a mean diabetes duration of 17.2 ± 12.7 years since diagnosis. Participants experienced a mean of 7.4 mild and 5.0 moderate hypoglycemic events per week and a mean of 3.6 SH events in the past year and 15.3 SH events (median 5 SH events) in their lifetime. Approximately half of the most recent SH events occurred in the 6 months immediately before the survey, emphasizing the relative frequency with which SH episodes occurred in the surveyed sample. The data on SH events in the 12 months before survey completion align with recent surveys of individuals with type 1 diabetes in other countries that reported means of 1.5–4.2 SH events in the previous 12 months (39,40). Importantly, CGM users among the surveyed sample continued to experience SH events, albeit fewer than non-CGM users. The reasons for this observation may be manifold, including lack of functional data because of system warm-up time, early termination, transmitter or receiver failure, or, more commonly, insufficient supply as a result of insurance problems.

Of note, the majority of participants in this study had received care from a paramedic (61.7%) or had an emergency department visit (58.5%), and more than one-third of participants (36.4%) had experienced a hospital stay of at least 1 night as a result of an SH event. These data illustrate the high level of health resource utilization as a direct consequence of SH, which is associated with significant costs to the U.S. health care system.

Importantly, the survey highlighted the emotional burden of SH on those affected, showing a considerable proportion of participants expressing worry or concern (67.7%), fear (54.4%), panic (52.5%), embarrassment (50.6%), and shame (21.2%) in connection with SH events. These findings are reflective of the findings of other recent survey studies on the negative emotional impact of SH on individuals with type 1 diabetes (3943).

Participants reported being aware of their hypoglycemia episodes primarily by experiencing symptoms and through the use of CGM; however, a substantial proportion (44.6%) reported impaired awareness of hypoglycemia. A high prevalence of hypoglycemia unawareness, even in those using CGM, has previously been reported; yet, the result from this survey was slightly higher than the rates noted in people with type 1 diabetes in other studies (39,40,42,44,45).

Nocturnal hypoglycemia and hypoglycemia during or after exercise were concerns for approximately three-fourths of the participants. Although we did not measure how often participants experienced nocturnal or exercise-related hypoglycemia, current research supports our participants’ concerns, indicating that 28.7–51.4% of participants’ most recent SH events occurred during the night (39,40,42). Both nocturnal hypoglycemia and exercise-related hypoglycemia are associated with immediate clinical consequences (46,47). Moreover, nocturnal hypoglycemia has a long-term impact on glucose counterregulatory mechanisms that may lead to cognitive impairment, reduced hypoglycemia awareness, and autonomic failure (47).

Importantly, this research study showed encouraging results, with 83.2% of the participants receiving education from their HCP pertaining to glucagon rescue use, although receiving care from an endocrinologist compared with other HCPs was not associated with perceived better education about glucagon use. However, this is an increase from the 71.0% of adults with type 1 diabetes who reported being educated by an HCP on this topic in a 2019 U.S. survey (21). Furthermore, almost all of the participants in the current study (97.2%) had been prescribed a glucagon rescue product at the time of the survey or in the past, 80.4% had a current prescription for glucagon, and 74.7% had a current prescription and had filled it. Participants with hypoglycemia unawareness were significantly more likely to have a current and filled glucagon prescription than those who had normal awareness of hypoglycemia. A possible explanation is that those with hypoglycemia unawareness may be more vigilant about having glucagon at their disposal because they are conscious of their own difficulty in recognizing symptoms of an oncoming SH episode. Those with a normal awareness of SH may be reassured that they can recognize symptoms of an oncoming SH episode and take evasive action (e.g., consuming oral carbohydrates) and thus may feel less reliant on glucagon.

The U.S. survey by Haymond et al. (21) noted that 85.2% (n = 225 of 264) of participating adults with type 1 diabetes had been prescribed glucagon and that 58.3% (n = 154 of 264) had a current glucagon prescription (21); 51% of those participants who had experienced an SH event in the past had not been able to have glucagon administered to them when needed, even if the kit was close by. In contrast, 14.9% of the participants in the present survey were unable to have glucagon administered to them when required. Thus, in addition to an increased number of people with type 1 diabetes being prescribed glucagon rescue therapy since 2019, the proportion of people who have been administered rescue glucagon when required has improved substantially. Nonetheless, this survey showed that known obstacles to the appropriate use of rescue glucagon (21,22,27) continue to pose challenges, including problems with the reconstitution and administration process, unawareness of the existence of the kit or inability to locate it, lack of training, kit expiration, and lack of confidence of the rescuing individual.

Participants who had never received a glucagon prescription (n = 9) stated that the main reasons for this were that their doctor had never discussed it with them, they carried oral carbohydrates with them, or they relied on CGM. A global survey report suggests differences among countries regarding the proportion of individuals with type 1 diabetes who were unable to have glucagon administered during an SH event because they did not have a glucagon prescription or it was not filled (39,40,42), ranging from 25.0% in a French cohort (42) to 68.8% in a Japanese cohort (39).

One of the most critical barriers to the use of glucagon rescue products identified in this study was a mean out-of-pocket cost of $73.40 ± $85.80 for glucagon kits. Cost was identified by 53.5% of participants as one of the improvements they would like to see in glucagon rescue products. Financial barriers may therefore contribute to people with type 1 diabetes not filling their glucagon prescriptions or relying on other means of achieving normoglycemia.

Our survey data further demonstrated that most participants preferred ready-to-use glucagon products over first-generation glucagon products that require reconstitution because of the former’s ease of use, ready-to-use administration format, fast onset of action, and storage at room temperature. Participants favored a nasal mode of administration (47.8%) and a premixed autoinjector (38.0%) over reconstituted first-generation glucagon (14.2%). When queried, at least half of the participants indicated that they would also like to see improvements in ease of use (62.7%) and more intuitive modes of administration (50.3%). This finding suggests that a large proportion of the participants may still use first-generation glucagon products that require complex reconstitution and administration steps.

Advice for Primary Care Providers

Despite the increasing use of CGM, SH and fear of SH continue to pose challenges for individuals with type 1 diabetes. Although the typical automated insulin delivery system responds by adjusting the insulin dose when an SH event occurs, this process does not obviate the immediate need for administration of counterregulatory glucagon. Thus, glucagon continues to be a necessary and potentially life-saving component of therapy for type 1 diabetes.

To provide the best possible care for individuals with type 1 diabetes, primary care providers are advised to follow the ADA’s guidelines for prescribing glucagon (3) and to address the following topics with their patients.

  • Ask whether the individual has a supply of glucagon at home.

    • If so, ascertain that the glucagon is not out of date.

    • If not, determine the barriers to accessing glucagon that the individual may face.

  • Ask about who in the individual’s support network is trained in glucagon use.

    • Ascertain whether these trusted individuals know where the glucagon is stored and are confident about administering it.

  • Given that ready-to-use glucagon products are now available, determine whether these individuals need to be retrained or whether additional people can be added to the individual’s circle of trusted individuals to optimize safety.

Limitations

A limitation of this study is that the surveyed sample is not representative of the overall population of people with type 1 diabetes in the United States. The survey sample was predominantly White and female and relatively young, affluent, and well-educated. The study design made use of an online survey format, and recruitment was conducted via digital media, which may have excluded people with limited computer skills or restricted computer or Internet access. The study included only adults with type 1 diabetes who had experienced at least one SH event in their lifetime and who were aware of the glucagon products on the market; therefore, the survey sample may be skewed toward people who were more aware of the available glucagon products than those who had never experienced an SH episode. In addition, the survey was conducted retrospectively, and data were self-reported, which carries the potential for misclassification of hypoglycemic events as well as recall bias, especially for the number of SH events in the participants’ lifetime. It was noted that a small number of participants reported a very high number of SH events in their lifetime (up to 1,000 events), which may have skewed the mean; the median may be more representative of the overall survey sample.

This study highlighted several important findings about the experiences of individuals with type 1 diabetes in the United States with SH and glucagon rescue use. The survey results suggest that the majority of individuals with type 1 diabetes have a current and filled prescription for rescue glucagon and have received education about glucagon rescue use from their HCP. The proportion of individuals with type 1 diabetes who were unable to have glucagon administered to them when required has decreased substantially compared with previous surveys. These data show a promising trend toward increased utilization of rescue glucagon and improved training in its use by HCPs in the past few years.

Despite these positive findings, there are continued challenges, including a high level of costly health care resource utilization directly resulting from SH events, substantial out-of-pocket expenses for glucagon kits, and a substantial prevalence of hypoglycemia unawareness. This study also highlighted the emotional burden of SH for individuals with type 1 diabetes.

Ready-to-use glucagon products do not yet seem to be fully adopted by HCPs and the diabetes community. Greater dissemination of these products among individuals with type 1 diabetes could improve the use of glucagon for SH rescue even more in the future. Further research is needed to understand experiences with and emotional effects of hypoglycemia and glucagon rescue use in both individuals with type 1 diabetes and their caregivers to improve the health and quality of life of people with type 1 diabetes.

Acknowledgments

The authors thank the people with type 1 diabetes who contributed to the focus groups and survey data. Medical writing and editorial assistance for this manuscript were provided by Claudia Brockmeyer, DPhil, Katharine Timberlake, DPhil, and Marlena Radomska, BSc, of Oxford PharmaGenesis, Oxford, U.K.

Funding

This study and the preparation of this article were funded by Zealand Pharma.

Duality of Interest

S.A.W. has received consulting fees from Zealand Pharma independent of the submitted work. M.W. is a former employee of Zealand Pharma. No other potential conflicts of interest relevant to this article were reported.

Author Contributions

A.S.H., K.S.C., J.L., J.B., and W.A.W. participated in the conceptualization and design of the study, enrolled the survey participants, and conducted the survey. A.S.H., K.S.C., and H.N. analyzed the survey data. H.N. conducted the correlation analysis. M.W. obtained funding for medical writing and editorial assistance. All of the authors interpreted the data, reviewed the manuscript critically for intellectual content, provided feedback for incorporation, and approved the final version for publication. A.S.H. is the guarantor of this work and, as such, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

J.L. is currently affiliated with Ironwood Pharmaceuticals, Boston, MA.

J.B. is currently affiliated with PatientsLikeMe, Boston, MA.

M.W. is currently affiliated with Market Access and RWE Consulting and Contract Services, Winget LLC, Boston, MA.

1.
Abraham
MB
,
Jones
TW
,
Naranjo
D
, et al
.
ISPAD Clinical Practice Consensus Guidelines 2018: Assessment and management of hypoglycemia in children and adolescents with diabetes
.
Pediatr Diabetes
2018
;
19
(
Suppl. 27
):
178
192
2.
Agiostratidou
G
,
Anhalt
H
,
Ball
D
, et al
.
Standardizing clinically meaningful outcome measures beyond HbA1c for type 1 diabetes: a consensus report of the American Association of Clinical Endocrinologists, the American Association of Diabetes Educators, the American Diabetes Association, the Endocrine Society, JDRF International, the Leona M. and Harry B. Helmsley Charitable Trust, the Pediatric Endocrine Society, and the T1D Exchange
.
Diabetes Care
2017
;
40
:
1622
1630
3.
American Diabetes Association Professional Practice Committee
.
6. Glycemic targets: Standards of Medical Care in Diabetes—2022
.
Diabetes Care
2022
;
45
(
Suppl. 1
):
S83
S96
4.
Cryer
PE
.
Mechanisms of hypoglycemia-associated autonomic failure in diabetes
.
N Engl J Med
2013
;
369
:
362
372
5.
Kahn
PA
,
Liu
S
,
McCoy
R
,
Gabbay
RA
,
Lipska
K
.
Glucagon use by U.S. adults with type 1 and type 2 diabetes
.
J Diabetes Complications
2021
;
35
:
107882
6.
Reno
CM
,
Litvin
M
,
Clark
AL
,
Fisher
SJ
.
Defective counterregulation and hypoglycemia unawareness in diabetes: mechanisms and emerging treatments
.
Endocrinol Metab Clin North Am
2013
;
42
:
15
38
7.
Gubitosi-Klug
RA
,
Braffett
BH
,
White
NH
, et al.;
Diabetes Control and Complications Trial (DCCT)/Epidemiology of Diabetes Interventions and Complications (EDIC) Research Group
.
Risk of severe hypoglycemia in type 1 diabetes over 30 years of follow-up in the DCCT/EDIC study
.
Diabetes Care
2017
;
40
:
1010
1016
8.
Khunti
K
,
Davies
M
,
Majeed
A
,
Thorsted
BL
,
Wolden
ML
,
Paul
SK
.
Hypoglycemia and risk of cardiovascular disease and all-cause mortality in insulin-treated people with type 1 and type 2 diabetes: a cohort study
.
Diabetes Care
2015
;
38
:
316
322
9.
Lu
CL
,
Shen
HN
,
Hu
SC
,
Wang
JD
,
Li
CY
.
A population-based study of all-cause mortality and cardiovascular disease in association with prior history of hypoglycemia among patients with type 1 diabetes
.
Diabetes Care
2016
;
39
:
1571
1578
10.
American Diabetes Association
.
Economic costs of diabetes in the U.S. in 2017
.
Diabetes Care
2018
;
41
:
917
928
11.
Foos
V
,
Varol
N
,
Curtis
BH
, et al
.
Economic impact of severe and non-severe hypoglycemia in patients with type 1 and type 2 diabetes in the United States
.
J Med Econ
2015
;
18
:
420
432
12.
Hinahara
J
,
Weinzimer
SA
,
Bromley
ER
,
Goss
TF
,
Kendall
DM
,
Hammer
M
.
Dasiglucagon demonstrates reduced costs in the treatment of severe hypoglycemia in a budget impact model
.
J Manag Care Spec Pharm
2022
;
28
:
461
472
13.
Edelman
S
,
Zhou
FL
,
Preblick
R
, et al
.
Burden of cardiovascular disease in adult patients with type 1 diabetes in the US
.
Pharmacoecon Open
2020
;
4
:
519
528
14.
Leon
BM
,
Maddox
TM
.
Diabetes and cardiovascular disease: epidemiology, biological mechanisms, treatment recommendations and future research
.
World J Diabetes
2015
;
6
:
1246
1258
15.
Sussman
M
,
Benner
J
,
Haller
MJ
,
Rewers
M
,
Griffiths
R
.
Estimated lifetime economic burden of type 1 diabetes
.
Diabetes Technol Ther
2020
;
22
:
121
130
16.
Jeon
JY
,
Kim
SR
,
Kim
HJ
, et al
.
Risk factors of severe hypoglycemia requiring medical assistance and neurological sequelae in patients with diabetes: a case-control study
.
Medicine (Baltimore)
2016
;
95
:
e5365
17.
Wild
D
,
von Maltzahn
R
,
Brohan
E
,
Christensen
T
,
Clauson
P
,
Gonder-Frederick
L
.
A critical review of the literature on fear of hypoglycemia in diabetes: implications for diabetes management and patient education
.
Patient Educ Couns
2007
;
68
:
10
15
18.
Willis
WD
,
Diago-Cabezudo
JI
,
Madec-Hily
A
,
Aslam
A
.
Medical resource use, disturbance of daily life and burden of hypoglycemia in insulin-treated patients with diabetes: results from a European online survey
.
Expert Rev Pharmacoecon Outcomes Res
2013
;
13
:
123
130
19.
Chapman
K
,
Hughes
AS
,
Bispham
J
,
Leon
C
,
Nguyen
H
,
Wolf
WA
.
Emergency glucagon: a focused review of psychosocial experiences of rescue drugs for type 1 diabetes
.
Curr Diab Rep
2022
;
22
:
189
197
20.
Fendrick
AM
,
He
X
,
Liu
D
,
Buxbaum
JD
,
Mitchell
BD
.
Glucagon prescriptions for diabetes patients after emergency department visits for hypoglycemia
.
Endocr Pract
2018
;
24
:
861
866
21.
Haymond
MW
,
Liu
J
,
Bispham
J
,
Hickey
A
,
McAuliffe-Fogarty
AH
.
Use of glucagon in patients with type 1 diabetes
.
Clin Diabetes
2019
;
37
:
162
166
22.
Kedia
N
.
Treatment of severe diabetic hypoglycemia with glucagon: an underutilized therapeutic approach
.
Diabetes Metab Syndr Obes
2011
;
4
:
337
346
23.
Mitchell
BD
,
He
X
,
Sturdy
IM
,
Cagle
AP
,
Settles
JA
.
Glucagon prescription patterns in patients with either type 1 or 2 diabetes with newly prescribed insulin
.
Endocr Pract
2016
;
22
:
123
135
24.
Eli Lilly and Company
.
Glucagon for injection prescribing information
.
Available from https://pi.lilly.com/us/rglucagon-pi.pdf. Accessed 31 May 2022
25.
Novo Nordisk
.
GlucaGen (glucagon) prescribing information
.
Available from https://www.novo-pi.com/glucagenhypokit.pdf. Accessed 31 May 2022
26.
Settles
JA
,
Gerety
GF
,
Spaepen
E
,
Suico
JG
,
Child
CJ
.
Nasal glucagon delivery is more successful than injectable delivery: a simulated severe hypoglycemia rescue
.
Endocr Pract
2020
;
26
:
407
415
27.
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
:
522
530
28.
Eli Lilly and Company
.
Baqsimi (glucagon) prescribing information
.
Available from https://pi.lilly.com/us/baqsimi-uspi.pdf. Accessed 31 May 2022
29.
Xeris Pharmaceuticals Inc
.
Gvoke (glucagon) prescribing information
.
30.
Zealand Pharma
.
Zegalogue (dasiglucagon) prescribing information
.
Available from https://www.novo-pi.com/zegalogue.pdf. Accessed 31 May 2022
31.
Laferrierre
K
,
Liu
J
,
Hughes
AS
,
Wolf
W
.
T1D Exchange registry: current data insights and future impact [Abstract]
.
Diabetes
2020
;
69
(
Suppl. 1
):
194-LB
32.
Leon
C
,
Liu
J
,
Ravelson
J
,
Chapman
KSM
,
Hughes
A
,
Wolf
W
.
T1D Exchange registry: current insights on participant outcomes [Abstract]
.
Diabetes
2021
;
70
(
Suppl. 1
):
186-LB
33.
T1D Exchange
.
T1D Exchange registry of people with type 1 diabetes in the United States
.
Available from https://t1dexchange.org/registry. Accessed 25 April 2022
34.
Alchemer
.
Alchemer survey software
.
Available from https://www.alchemer.com. Accessed 20 May 2021
35.
Gold
AE
,
MacLeod
KM
,
Frier
BM
.
Frequency of severe hypoglycemia in patients with type I diabetes with impaired awareness of hypoglycemia
.
Diabetes Care
1994
;
17
:
697
703
36.
Muradoğlu
S
,
Yeşiltepe Mutlu
G
,
Gökçe
T
,
Can
E
,
Hatun
Ş
.
An evaluation of glucagon injection anxiety and its association with the fear of hypoglycemia among the parents of children with type 1 diabetes
.
J Clin Res Pediatr Endocrinol
2021
;
13
:
285
292
37.
Patton
SR
,
Dolan
LM
,
Henry
R
,
Powers
SW
.
Parental fear of hypoglycemia: young children treated with continuous subcutaneous insulin infusion
.
Pediatr Diabetes
2007
;
8
:
362
368
38.
Patton
SR
,
Dolan
LM
,
Smith
LB
,
Thomas
IH
,
Powers
SW
.
Pediatric parenting stress and its relation to depressive symptoms and fear of hypoglycemia in parents of young children with type 1 diabetes mellitus
.
J Clin Psychol Med Settings
2011
;
18
:
345
352
39.
Iwahori
T
,
Snoek
F
,
Nagai
Y
,
Spaepen
E
,
Mitchell
BD
,
Peyrot
M
.
Conversations and Reactions Around Severe Hypoglycemia (CRASH): Japan results from a global survey of people with T1DM or insulin-treated T2DM and caregivers
.
Diabetes Ther
2022
;
13
:
517
533
40.
Mojdami
D
,
Mitchell
BD
,
Spaepen
E
, et al
.
Conversations and reactions around severe hypoglycemia study: results of hypoglycemia experiences in Canadian adults with insulin-treated diabetes and their caregivers
.
Can J Diabetes
2021
;
45
:
236
242
41.
Ampudia-Blasco
FJ
,
Artime
E
,
Díaz
S
, et al
.
Conversations and Reactions Around Severe Hypoglycaemia (CRASH): Spanish results of a global survey of people with type 1 diabetes or insulin-treated type 2 diabetes and caregivers
.
Endocrinol Diabetes Nutr (Engl Ed)
2021
;
68
:
557
566
42.
Chevalier
N
,
Penfornis
A
,
Riveline
JP
, et al
.
Conversations and Reactions Around Severe Hypoglycemia (CRASH) global survey of people with type 1 diabetes or insulin-treated type 2 diabetes and caregivers: findings from the French cohort
.
Ann Endocrinol (Paris)
2022
;
83
:
16
26
43.
Mönnig
E
,
Spaepen
E
,
Osumili
B
, et al
.
Conversations and Reactions Around Severe Hypoglycaemia (CRASH): results from the German cohort of a global survey of people with type 1 diabetes or insulin-treated type 2 diabetes and caregivers
.
Exp Clin Endocrinol Diabetes
2022
;
130
:
145
155
44.
Porcellati
F
,
Di Mauro
S
,
Mazzieri
A
, et al
.
Glucagon as a therapeutic approach to severe hypoglycemia: after 100 years, is it still the antidote of insulin?
Biomolecules
2021
;
11
:
1281
45.
Olsen
SE
,
Asvold
BO
,
Frier
BM
,
Aune
SE
,
Hansen
LI
,
Bjørgaas
MR
.
Hypoglycaemia symptoms and impaired awareness of hypoglycaemia in adults with type 1 diabetes: the association with diabetes duration
.
Diabet Med
2014
;
31
:
1210
1217
46.
Cockcroft
EJ
,
Narendran
P
,
Andrews
RC
.
Exercise-induced hypoglycaemia in type 1 diabetes
.
Exp Physiol
2020
;
105
:
590
599
47.
Edelman
SV
,
Blose
JS
.
The impact of nocturnal hypoglycemia on clinical and cost-related issues in patients with type 1 and type 2 diabetes
.
Diabetes Educ
2014
;
40
:
269
279
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