Mini-Dose Glucagon to Treat Non-Severe Hypoglycemia

• Sponsor: Jaeb Center for Health Research (Other)
• Overall Status: Completed
• CT.gov ID: NCT02411578
• Collaborator: Xeris Pharmaceuticals (Industry)
• Enrollment: 26
• Locations: 5
• Arms: 2
• Duration (Months): 8
• Patients Per Site: 5.2
• Patients Per Site Per Month: 0.7

Study Details

Study Description

Brief Summary

The purpose of this study is to determine if a small dose of glucagon (mini-dose glucagon) is effective for the treatment of non-severe hypoglycemia in adults with type 1 diabetes (T1D).

Condition or Disease	Intervention/Treatment	Phase
Diabetes Mellitus, Type 1	Drug: G-Pen Mini™ (glucagon injection); Other: Glucose Tablets	Phase 2

Detailed Description

There are three phases included in this study: (1) Pre-crossover Trial Run-in Phase, (2) Randomized Clinical Trial (RCT) Crossover Trial Phase, and (3) Post-Crossover Trial Extension Phase.

1. Run-in Phase:

Prior to commencing the crossover trial, study enrollment will begin with a 2 week run-in phase to assess hypoglycemia eligibility and compliance.

1. Crossover Trial Phase:

The Crossover Trial Phase will consist of two (3-week) periods.

The Crossover Trial Phase will include up to 24 participants who complete these study periods. Participants who do not complete both periods or who do not have at least one event during both periods may be replaced.

During the Crossover Trial Phase participants will be randomized into two groups: (1) Group A will use mini-dose glucagon in period 1 and oral glucose tablets in period 2 and (2) Group B will use oral glucose tablets in period 1 and mini-dose glucagon in period 2. Each group with follow the applicable treatment arm according to their randomized group.

1. Extension Phase:

The Post-Crossover Trial phase will commence upon completion of the second 3-week period of the Crossover Trial Phase. Participants will have a 3 week phase during which time they will decide whether to use mini-dose glucagon or glucose tablets to treat each non-severe hypoglycemic event or to prevent hypoglycemia.

Study Design

• Study Type: Interventional
• Actual Enrollment: 26 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Mini-Dose Glucagon for Adults With Type 1 Diabetes: A Study to Assess the Efficacy and Safety of Mini-dose Glucagon for Treatment of Non-severe Hypoglycemia in Adults With Type 1 Diabetes
• Study Start Date: Sep 1, 2015
• Actual Primary Completion Date: Apr 1, 2016
• Actual Study Completion Date: May 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: G-Pen Mini™ (glucagon injection) Participants are to check blood glucose (BG) with study meter once their continuous glucose monitor (CGM) reads <70 mg/dl or they experience symptoms. Participants will be instructed to treat using mini-dose glucagon for certain phases/periods when BG is 40 to 69 mg/dl (considered a non-severe hypoglycemic event). For every event, participant will check BG with meter 3 times and treat according to protocol instructions based on BG measurement.	Drug: G-Pen Mini™ (glucagon injection); 1st BG check, 1st treatment BG is 50-69 mg/dl, treatment is 150 µg of glucagon BG is 40-49 mg/dl, treatment is 300 µg of glucagon 15 min later, 2nd BG check, 2nd treatment BG is 60-69 mg/dl, no treatment BG is 50-59 mg/dl, treatment is 150 µg of glucagon BG is <50 mg/dl, treatment is participant's preferred oral carbohydrate and not mini-dose glucagon 30 minutes later, 3rd BG check, 3rd treatment BG is >=70, no treatment BG is <70 mg/dl, treatment is participant's preferred oral carbohydrate and not mini-dose glucagon (150 µg of glucagon per syringe); Other Names: mini-dose glucagon
Active Comparator: Glucose Tabs Participants are to check their blood glucose (BG) with study meter once their continuous glucose meter reads <70 mg/dl or they experience symptoms. Participants will be instructed to treat using oral glucose tablets for certain phases/periods when BG is 40 to 69 mg/dl (considered a non-severe hypoglycemic event). For every event, participant will check BG with meter 3 times and treat according to protocol instructions based on BG measurement.	Other: Glucose Tablets; 1st BG check, 1st treatment BG is 50-69 mg/dl, treatment is 15 grams of carbohydrates BG is 40-49 mg/dl, treatment is 30 grams of carbohydrates 15 min later, 2nd BG check, 2nd treatment BG is 60-69 mg/dl, no treatment BG is 50-59 mg/dl, treatment is 15 grams of carbohydrates BG is <50 mg/dl, treatment is participant's preferred oral carbohydrate and not mini-dose glucagon 30 minutes later, 3rd BG check, 3rd treatment BG is >=70, no treatment BG is <70 mg/dl, treatment is participant's preferred oral carbohydrate and not mini-dose glucagon (5 grams of fast-acting carbohydrates (D-Glucose) per tablet); Other Names: over-the-counter oral glucose tablets; glucose tabs

Outcome Measures

Primary Outcome Measures

1. Number of Hypoglycemic Events ≥50 mg/dl 15 Minutes AND ≥ 70 mg/dl 30 Minutes After Initial Treatment [30 minutes]

Secondary Outcome Measures

1. Continuous Glucose Monitor (CGM) Minimum Glucose, Event Level [60 Minutes]

   Minimum glucose from CGM data, following each hypoglycemic event with starting BG 50-69 mg/dL, during first hour after start of hypoglycemic event

2. CGM Maximum Glucose, Event Level [60 Minutes]

   Maximum glucose from CGM data, following each hypoglycemic event with starting BG 50-69 mg/dL, during first hour after start of hypoglycemic event

3. CGM Mean Glucose, Event Level [60 Minutes]

   Median (IQR) reported for mean glucose from CGM data, following each hypoglycemic event with starting BG 50-69 mg/dL, during first hour after start of hypoglycemic event

4. CGM Time in Range, Event Level [60 Minutes]

   Percentage of time 70-180 mg/dL from CGM data, following each hypoglycemic event with starting BG 50-69 mg/dL, during first hour after start of hypoglycemic event

5. CGM Time Below 70 mg/dL, Event Level [60 Minutes]

   Percentage of time <70 mg/dL from CGM data, following each hypoglycemic event with starting BG 50-69 mg/dL, during first hour after start of hypoglycemic event

6. CGM Minimum Glucose, Event Level [120 Minutes]

   Minimum glucose from CGM data, following each hypoglycemic event with starting BG 50-69 mg/dL, during first 2 hours after start of hypoglycemic event

7. CGM Maximum Glucose, Event Level [120 Minutes]

   Maximum glucose from CGM data, following each hypoglycemic event with starting BG 50-69 mg/dL, during first 2 hours after start of hypoglycemic event

8. CGM Mean Glucose, Event Level [120 Minutes]

   Median (IQR) reported for mean glucose from CGM data, following each hypoglycemic event with starting BG 50-69 mg/dL, during first 2 hours after start of hypoglycemic event

9. CGM Time in Range, Event Level [120 Minutes]

   Percentage of time 70-180 mg/dL from CGM data, following each hypoglycemic event with starting BG 50-69 mg/dL, during first 2 hours after start of hypoglycemic event

10. CGM Time Below 70 mg/dL [120 Minutes]

    Percentage of time <70 mg/dL from CGM data, following each hypoglycemic event with starting BG 50-69 mg/dL, during first 2 hours after start of hypoglycemic event

11. CGM Mean Glucose [3 weeks]

    Median (IQR) reported for mean glucose from CGM data computed over entire 3 weeks of treatment period

12. CGM Time in Range [3 weeks]

    Percentage of time 70-180 mg/dL from CGM data computed over entire 3 weeks of treatment period

13. CGM Time Below 70 [3 weeks]

    Percentage of time <70 mg/dL from CGM data computed over entire 3 weeks of treatment period

14. CGM Coefficient of Variation [3 weeks]

    Coefficient of Variation from CGM data computed over entire 3 weeks of treatment period

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 64 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Clinical diagnosis of presumed autoimmune T1D and receiving daily insulin

2. Age: 18.0 to < 65.0 years

3. Duration of T1D: ≥2.0 years

4. Body mass index 20.0 to <35.0 kg/m2 and weight 110 to <250 lbs

5. HbA1c <8.5% (point of care or local lab, within past month)

6. Using continuous subcutaneous insulin infusion (CSII) therapy (i.e., insulin pump) for at least 3 months, with no plans to discontinue use during the study (and no use of active low glucose suspend feature within the last 4 weeks)

7. Using continuous glucose monitor ≥6 days/week in the last 4 weeks, with no plans to discontinue continuous glucose monitor use during the study

8. Continuous glucose monitor glucose level <70 mg/dl during daytime hours (e.g., 8am - 10pm) on at least 7 of the past 28 days (a modification can be made for participants with non-traditional waking hours) evaluated from downloaded CGM data

9. Females must meet one of the following criteria:

• Of childbearing potential and not currently pregnant (negative pregnancy test) or lactating, and agrees to use an accepted contraceptive regimen as described in the study procedure manual throughout the entire duration of the study (from screening visit until study completion); or

• Of non-childbearing potential, defined as a female who has had a hysterectomy or tubal ligation, is clinically considered infertile or is in a menopausal state (at least 1 year without menses)

1. In good general health with no conditions that could influence the outcome of the trial, and in the judgment of the investigator is a good candidate for the study based on review of available medical history, physical examination and clinical laboratory evaluations

2. Willing to adhere to the protocol requirements for the duration of the study

3. Participant has a smart phone available and is able to use it daily

4. Must be enrolled in the T1D Exchange clinic registry or willing to join the clinic registry

Exclusion Criteria:

1. More than 1 severe hypoglycemic episode in the past 12 months (as defined by an episode that required third party assistance for treatment)

2. More than 1 episode of diabetic ketoacidosis in the past 12 months (as defined by an episode diagnosed as diabetic ketoacidosis that required treatment in an emergency department or hospitalization)

3. Presence of cardiovascular, gastrointestinal, liver or kidney disease, or any medical condition which, in the judgment of the investigator, could potentiate or predispose to undesired effects or could interfere with the absorption, distribution, metabolism, or excretion of glucagon or ability to respond appropriately to mild to moderate hypoglycemia.

4. Known presence of hereditary problems of glycogen storage disease, galactose and/or lactose intolerance

5. Males with alcohol use in excess of 3 or more drinks per day, on average and females with alcohol use in excess of 2 or more drinks per day, on average

6. Use of non-insulin anti-diabetic medications

7. Use of daily systemic beta-blocker

8. Use of beta-adrenergic agonists, theophylline (or other methylxanthines)

9. Use of 1st generation anticholinergic drugs (such as Brompheniramine, Chlorpheniramine, Dimenhydrinate, Diphenhydramine, and Doxylamine)

10. Use of systemic corticosteroids

11. History of hypersensitivity to glucagon or any related product or excipient or severe hypersensitivity reactions (such as angioedema) to any drugs

12. History of epilepsy or seizure disorder

13. Uncontrolled hypertension, >160 mmHg systolic or >100 mmHg diastolic

14. Currently a high endurance exerciser or plans to perform high endurance exercise during study (from screening visit until study completion)

• High endurance exerciser defined as a person who regularly competes in running, cycling, rowing, swimming or any other endurance-based activity for the purpose of competition (>2100 metabolic equivalent of task (MET) minutes per week [i.e. 7 METs x 60 minutes x 5 days a week, where 7 METs is equivalent to jogging])

1. Currently following a very low calorie or other weight-loss diet

2. Participation in other studies involving administration of an investigational drug or device within 30 days or 5 half-lives, whichever is longer, before screening for the current study or planning to participate in another such study during participation in the current study

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Colorado/Barbara Davis Center for Diabetes	Aurora	Colorado	United States	80045
2	Yale University of Medicine	New Haven	Connecticut	United States	06510
3	Joslin Diabetes Center	Boston	Massachusetts	United States	02215
4	SUNY Upstate Medical University	Syracuse	New York	United States	13210
5	University of Pennsylvania	Philadelphia	Pennsylvania	United States	19104

Sponsors and Collaborators

• Jaeb Center for Health Research
• Xeris Pharmaceuticals

Investigators

• Study Chair: Morey W Haymond, MD, Baylor College of Medicine
• Principal Investigator: Stephanie N DuBose, MPH, Jaeb Center for Health Research

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Safety and Efficacy Study of Mini-Dose Glucagon (G-Pen Mini) in Patients With Type 1 Diabetes

Publications

• Cryer PE. Hypoglycemia in type 1 diabetes mellitus. Endocrinol Metab Clin North Am. 2010 Sep;39(3):641-54. doi: 10.1016/j.ecl.2010.05.003. Review.
• Cryer PE. The barrier of hypoglycemia in diabetes. Diabetes. 2008 Dec;57(12):3169-76. doi: 10.2337/db08-1084. Review.
• Hartley M, Thomsett MJ, Cotterill AM. Mini-dose glucagon rescue for mild hypoglycaemia in children with type 1 diabetes: the Brisbane experience. J Paediatr Child Health. 2006 Mar;42(3):108-11.
• Hasan KS, Kabbani M. Mini-dose glucagon is effective at diabetes camp. J Pediatr. 2004 Jun;144(6):834.
• Haymond MW, Schreiner B. Mini-dose glucagon rescue for hypoglycemia in children with type 1 diabetes. Diabetes Care. 2001 Apr;24(4):643-5.
• Juvenile Diabetes Research Foundation Continuous Glucose Monitoring Study Group, Beck RW, Hirsch IB, Laffel L, Tamborlane WV, Bode BW, Buckingham B, Chase P, Clemons R, Fiallo-Scharer R, Fox LA, Gilliam LK, Huang ES, Kollman C, Kowalski AJ, Lawrence JM, Lee J, Mauras N, O'Grady M, Ruedy KJ, Tansey M, Tsalikian E, Weinzimer SA, Wilson DM, Wolpert H, Wysocki T, Xing D. The effect of continuous glucose monitoring in well-controlled type 1 diabetes. Diabetes Care. 2009 Aug;32(8):1378-83. doi: 10.2337/dc09-0108. Epub 2009 May 8.
• Raju B, Arbelaez AM, Breckenridge SM, Cryer PE. Nocturnal hypoglycemia in type 1 diabetes: an assessment of preventive bedtime treatments. J Clin Endocrinol Metab. 2006 Jun;91(6):2087-92. Epub 2006 Feb 21.

• Responsible Party: Jaeb Center for Health Research
• ClinicalTrials.gov Identifier: NCT02411578
• Other Study ID Numbers: T1DX Mini-dose Non-Severe
• First Posted: Apr 8, 2015
• Last Update Posted: Mar 3, 2020
• Last Verified: Feb 1, 2020

• Keywords provided by Jaeb Center for Health Research: T1D; Type 1 diabetes; Mini-dose glucagon; adults; non-severe hypoglycemia
• Additional relevant MeSH terms: Hypoglycemia; Diabetes Mellitus, Type 1; Glucagon; Glucagon-Like Peptide 1

Study Results

Participant Flow

Pre-assignment Detail	26 consented for Run-in; 1 ineligible after consent; 2 ineligible after Run-in phase; 3 withdrew

Arm/Group Title	G-Pen Mini™ (Glucagon Injection), Then Glucose Tabs	Glucose Tabs, Then G-Pen Mini
Arm/Group Description	For G-Pen Mini Period: Participants are to check blood glucose (BG) with study meter if continuous glucose monitor (CGM) reads <70 mg/dl or they experience symptoms. Participants instructed to treat using mini-dose glucagon for certain phases/periods when BG is 40 to 69 mg/dl (considered a non-severe hypoglycemic event). G-Pen Mini™ (glucagon injection): 1st BG check, 1st treatment BG is 50-69 mg/dl, treatment is 150 µg of glucagon BG is 40-49 mg/dl, treatment is 300 µg of glucagon 15 min later, 2nd BG check, 2nd treatment BG is 60-69 mg/dl, no treatment BG is 50-59 mg/dl, treatment is 150 µg of glucagon BG is <50 mg/dl, treatment is participant's preferred oral carbohydrate and not mini-dose glucagon 30 minutes later, 3rd BG check, 3rd treatment BG is >=70, no treatment BG is <70 mg/dl, treatment is participant's preferred oral carbohydrate and not mini-dose glucagon	For Glucose Tabs Period: Participants are to check blood glucose (BG) with study meter if continuous glucose meter reads <70 mg/dl or they experience symptoms. Participants instructed to treat using oral glucose tablets for certain phases/periods when BG is 40 to 69 mg/dl (considered a non-severe hypoglycemic event). Glucose Tabs: 1st BG check, 1st treatment: BG is 50-69 mg/dl, treatment is 15 grams of carbohydrates BG is 40-49 mg/dl, treatment is 30 grams of carbohydrates 15 min later, 2nd BG check, 2nd treatment BG is 60-69 mg/dl, no treatment BG is 50-59 mg/dl, treatment is 15 grams of carbohydrates BG is <50 mg/dl, treatment is participant's preferred oral carbohydrate and not mini-dose glucagon 30 minutes later, 3rd BG check, 3rd treatment BG is >=70 mg/dl, no treatment BG is <70 mg/dl, treatment is participant's preferred oral carbohydrate and not mini-dose glucagon
Period Title: Crossover Trial Phase
STARTED	8	12
COMPLETED	8	11
NOT COMPLETED	0	1
Period Title: Crossover Trial Phase
STARTED	8	9
COMPLETED	8	9
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	G-Pen Mini™ (Glucagon Injection), Then Glucose Tabs	Glucose Tabs, Then G-Pen Mini	Total
Arm/Group Description	For G-Pen Mini Period: Participants are to check blood glucose (BG) with study meter if continuous glucose monitor (CGM) reads <70 mg/dl or they experience symptoms. Participants instructed to treat using mini-dose glucagon for certain phases/periods when BG is 40 to 69 mg/dl (considered a non-severe hypoglycemic event). G-Pen Mini™ (glucagon injection): 1st BG check, 1st treatment BG is 50-69 mg/dl, treatment is 150 µg of glucagon BG is 40-49 mg/dl, treatment is 300 µg of glucagon 15 min later, 2nd BG check, 2nd treatment BG is 60-69 mg/dl, no treatment BG is 50-59 mg/dl, treatment is 150 µg of glucagon BG is <50 mg/dl, treatment is participant's preferred oral carbohydrate and not mini-dose glucagon 30 minutes later, 3rd BG check, 3rd treatment BG is >=70, no treatment BG is <70 mg/dl, treatment is participant's preferred oral carbohydrate and not mini-dose glucagon	For Glucose Tabs Period: Participants are to check blood glucose (BG) with study meter if continuous glucose meter reads <70 mg/dl or they experience symptoms. Participants instructed to treat using oral glucose tablets for certain phases/periods when BG is 40 to 69 mg/dl (considered a non-severe hypoglycemic event). Glucose Tabs: 1st BG check, 1st treatment: BG is 50-69 mg/dl, treatment is 15 grams of carbohydrates BG is 40-49 mg/dl, treatment is 30 grams of carbohydrates 15 min later, 2nd BG check, 2nd treatment BG is 60-69 mg/dl, no treatment BG is 50-59 mg/dl, treatment is 15 grams of carbohydrates BG is <50 mg/dl, treatment is participant's preferred oral carbohydrate and not mini-dose glucagon 30 minutes later, 3rd BG check, 3rd treatment BG is >=70 mg/dl, no treatment BG is <70 mg/dl, treatment is participant's preferred oral carbohydrate and not mini-dose glucagon	Total of all reporting groups
Overall Participants	6	10	16
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	41.5 (9.1)	36.9 (12.2)	38.6 (11.0)
Sex: Female, Male (Count of Participants)
Female	3 50%	9 90%	12 75%
Male	3 50%	1 10%	4 25%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%
Not Hispanic or Latino	6 100%	10 100%	16 100%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%
White	6 100%	10 100%	16 100%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Hemoglobin A1c (%) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [%]	6.9 (0.6)	7.4 (0.9)	7.2 (0.8)
Duration of Type 1 Diabetes (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	24.8 (14.2)	22.5 (15.8)	23.4 (14.8)

Outcome Measures

1. Primary Outcome

Title	Number of Hypoglycemic Events ≥50 mg/dl 15 Minutes AND ≥ 70 mg/dl 30 Minutes After Initial Treatment
Time Frame	30 minutes

Outcome Measure Data

Analysis Population Description

Limited to events with starting BG of 50-69 mg/dL

Arm/Group Title	G-Pen Mini™ (Glucagon Injection)	Glucose Tabs
Arm/Group Description	For G-Pen Mini period: Participants are to check blood glucose (BG) with study meter if continuous glucose monitor (CGM) reads <70 mg/dl or they experience symptoms. Participants instructed to treat using mini-dose glucagon for certain phases/periods when BG is 40 to 69 mg/dl (considered a non-severe hypoglycemic event). G-Pen Mini™ (glucagon injection): 1st BG check, 1st treatment BG is 50-69 mg/dl, treatment is 150 µg of glucagon BG is 40-49 mg/dl, treatment is 300 µg of glucagon 15 min later, 2nd BG check, 2nd treatment BG is 60-69 mg/dl, no treatment BG is 50-59 mg/dl, treatment is 150 µg of glucagon BG is <50 mg/dl, treatment is participant's preferred oral carbohydrate and not mini-dose glucagon 30 minutes later, 3rd BG check, 3rd treatment BG is >=70, no treatment BG is <70 mg/dl, treatment is participant's preferred oral carbohydrate and not mini-dose glucagon	For Glucose Tabs Period: Participants are to check blood glucose (BG) with study meter if continuous glucose meter reads <70 mg/dl or they experience symptoms. Participants instructed to treat using oral glucose tablets for certain phases/periods when BG is 40 to 69 mg/dl (considered a non-severe hypoglycemic event). Glucose Tabs: 1st BG check, 1st treatment: BG is 50-69 mg/dl, treatment is 15 grams of carbohydrates BG is 40-49 mg/dl, treatment is 30 grams of carbohydrates 15 min later, 2nd BG check, 2nd treatment BG is 60-69 mg/dl, no treatment BG is 50-59 mg/dl, treatment is 15 grams of carbohydrates BG is <50 mg/dl, treatment is participant's preferred oral carbohydrate and not mini-dose glucagon 30 minutes later, 3rd BG check, 3rd treatment BG is >=70 mg/dl, no treatment BG is <70 mg/dl, treatment is participant's preferred oral carbohydrate and not mini-dose glucagon
Measure Participants	16	16
Measure Hypoglycemic Events	62	56
Count of Units [Hypoglycemic Events]	58	53

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	G-Pen Mini™ (Glucagon Injection), Glucose Tabs
	Comments	For the crossover trial primary analysis, analyzed events were study treatment events meeting the following criteria: a) a survey was completed in the smart phone application, b) the initial BG measurement was 40 to 69 mg/dL, c) BG measurements were performed at both the 15-minute (in a window of 13 to 20 minutes) and 30-minute (28 to 40 minutes) time points, and d) appropriate treatment including dose was taken both at the initial and 15-minute time points.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.99
	Comments	Proportions of successes in each arm were compared using a generalized linear mixed model with a logistic link function, random participant effect to account for correlated data from some pts having multiple events, and adjustment for baseline BG.
	Method	Mixed Models Analysis
	Comments

2. Secondary Outcome

Title	Continuous Glucose Monitor (CGM) Minimum Glucose, Event Level
Description	Minimum glucose from CGM data, following each hypoglycemic event with starting BG 50-69 mg/dL, during first hour after start of hypoglycemic event
Time Frame	60 Minutes

Outcome Measure Data

Analysis Population Description

A participant had to have sufficient calibrations using study BGM to compare BGM and CGM data to ensure matching dates and times. Event level requirements: 1) initial treatment and dose had to be correct, 2) ≥6 CGM readings within 1 hour after initial treatment, and 3) first CGM glucose after the start of the hypoglycemic event had to be <80 mg/dL

Arm/Group Title	G-Pen Mini™ (Glucagon Injection)	Glucose Tabs
Arm/Group Description	For G-Pen Mini Period: Participants are to check blood glucose (BG) with study BG meter (BGM) if continuous glucose monitor (CGM) reads <70 mg/dl or they experience symptoms. Participants instructed to treat using mini-dose glucagon for certain phases/periods when BG is 40 to 69 mg/dl (considered a non-severe hypoglycemic event). G-Pen Mini™ (glucagon injection): 1st BG check, 1st treatment BG is 50-69 mg/dl, treatment is 150 µg of glucagon BG is 40-49 mg/dl, treatment is 300 µg of glucagon 15 min later, 2nd BG check, 2nd treatment BG is 60-69 mg/dl, no treatment BG is 50-59 mg/dl, treatment is 150 µg of glucagon BG is <50 mg/dl, treatment is participant's preferred oral carbohydrate and not mini-dose glucagon 30 minutes later, 3rd BG check, 3rd treatment BG is >=70, no treatment BG is <70 mg/dl, treatment is participant's preferred oral carbohydrate and not mini-dose glucagon	For Glucose Tabs Period: Participants are to check blood glucose (BG) with study meter if continuous glucose meter reads <70 mg/dl or they experience symptoms. Participants instructed to treat using oral glucose tablets for certain phases/periods when BG is 40 to 69 mg/dl (considered a non-severe hypoglycemic event). Glucose Tabs: 1st BG check, 1st treatment: BG is 50-69 mg/dl, treatment is 15 grams of carbohydrates BG is 40-49 mg/dl, treatment is 30 grams of carbohydrates 15 min later, 2nd BG check, 2nd treatment BG is 60-69 mg/dl, no treatment BG is 50-59 mg/dl, treatment is 15 grams of carbohydrates BG is <50 mg/dl, treatment is participant's preferred oral carbohydrate and not mini-dose glucagon 30 minutes later, 3rd BG check, 3rd treatment BG is >=70 mg/dl, no treatment BG is <70 mg/dl, treatment is participant's preferred oral carbohydrate and not mini-dose glucagon
Measure Participants	15	15
Measure Hypoglycemic Events	48	36
Median (Inter-Quartile Range) [mg/dL]	59	56

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	G-Pen Mini™ (Glucagon Injection), Glucose Tabs
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.34
	Comments
	Method	Mixed Models Analysis
	Comments	Analyzed with generalized linear mixed model with an identity link. Due to violations of normality, rank transformations were used in model.

3. Secondary Outcome

Title	CGM Maximum Glucose, Event Level
Description	Maximum glucose from CGM data, following each hypoglycemic event with starting BG 50-69 mg/dL, during first hour after start of hypoglycemic event
Time Frame	60 Minutes

Outcome Measure Data

Analysis Population Description

A participant had to have sufficient calibrations using study BGM to compare BGM and CGM data to ensure matching dates and times. Event level requirements: 1) initial treatment and dose had to be correct, 2) ≥6 CGM readings within 1 hour after initial treatment, and 3) first CGM glucose after the start of the hypoglycemic event had to be <80 mg/dL

Arm/Group Title	G-Pen Mini™ (Glucagon Injection)	Glucose Tabs
Arm/Group Description	For G-Pen Mini Period: Participants are to check blood glucose (BG) with study meter if continuous glucose monitor (CGM) reads <70 mg/dl or they experience symptoms. Participants instructed to treat using mini-dose glucagon for certain phases/periods when BG is 40 to 69 mg/dl (considered a non-severe hypoglycemic event). G-Pen Mini™ (glucagon injection): 1st BG check, 1st treatment BG is 50-69 mg/dl, treatment is 150 µg of glucagon BG is 40-49 mg/dl, treatment is 300 µg of glucagon 15 min later, 2nd BG check, 2nd treatment BG is 60-69 mg/dl, no treatment BG is 50-59 mg/dl, treatment is 150 µg of glucagon BG is <50 mg/dl, treatment is participant's preferred oral carbohydrate and not mini-dose glucagon 30 minutes later, 3rd BG check, 3rd treatment BG is >=70, no treatment BG is <70 mg/dl, treatment is participant's preferred oral carbohydrate and not mini-dose glucagon	For Glucose Tabs Period: Participants are to check blood glucose (BG) with study meter if continuous glucose meter reads <70 mg/dl or they experience symptoms. Participants instructed to treat using oral glucose tablets for certain phases/periods when BG is 40 to 69 mg/dl (considered a non-severe hypoglycemic event). Glucose Tabs: 1st BG check, 1st treatment: BG is 50-69 mg/dl, treatment is 15 grams of carbohydrates BG is 40-49 mg/dl, treatment is 30 grams of carbohydrates 15 min later, 2nd BG check, 2nd treatment BG is 60-69 mg/dl, no treatment BG is 50-59 mg/dl, treatment is 15 grams of carbohydrates BG is <50 mg/dl, treatment is participant's preferred oral carbohydrate and not mini-dose glucagon 30 minutes later, 3rd BG check, 3rd treatment BG is >=70 mg/dl, no treatment BG is <70 mg/dl, treatment is participant's preferred oral carbohydrate and not mini-dose glucagon
Measure Participants	15	15
Measure Hypoglycemic Events	48	36
Median (Inter-Quartile Range) [mg/dL]	102	116

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	G-Pen Mini™ (Glucagon Injection), Glucose Tabs
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.01
	Comments
	Method	Mixed Models Analysis
	Comments	Analyzed with generalized linear mixed model with an identity link. Due to violations of normality, rank transformations were used in model.

4. Secondary Outcome

Title	CGM Mean Glucose, Event Level
Description	Median (IQR) reported for mean glucose from CGM data, following each hypoglycemic event with starting BG 50-69 mg/dL, during first hour after start of hypoglycemic event
Time Frame	60 Minutes

Outcome Measure Data

Analysis Population Description

A participant had to have sufficient calibrations using study BGM to compare BGM and CGM data to ensure matching dates and times. Event level requirements: 1) initial treatment and dose had to be correct, 2) ≥6 CGM readings within 1 hour after initial treatment, and 3) first CGM glucose after the start of the hypoglycemic event had to be <80 mg/dL

Arm/Group Title	G-Pen Mini™ (Glucagon Injection)	Glucose Tabs
Arm/Group Description	For G-Pen Mini Period: Participants are to check blood glucose (BG) with study meter if continuous glucose monitor (CGM) reads <70 mg/dl or they experience symptoms. Participants instructed to treat using mini-dose glucagon for certain phases/periods when BG is 40 to 69 mg/dl (considered a non-severe hypoglycemic event). G-Pen Mini™ (glucagon injection): 1st BG check, 1st treatment BG is 50-69 mg/dl, treatment is 150 µg of glucagon BG is 40-49 mg/dl, treatment is 300 µg of glucagon 15 min later, 2nd BG check, 2nd treatment BG is 60-69 mg/dl, no treatment BG is 50-59 mg/dl, treatment is 150 µg of glucagon BG is <50 mg/dl, treatment is participant's preferred oral carbohydrate and not mini-dose glucagon 30 minutes later, 3rd BG check, 3rd treatment BG is >=70, no treatment BG is <70 mg/dl, treatment is participant's preferred oral carbohydrate and not mini-dose glucagon	For Glucose Tabs Period: Participants are to check blood glucose (BG) with study meter if continuous glucose meter reads <70 mg/dl or they experience symptoms. Participants instructed to treat using oral glucose tablets for certain phases/periods when BG is 40 to 69 mg/dl (considered a non-severe hypoglycemic event). Glucose Tabs: 1st BG check, 1st treatment: BG is 50-69 mg/dl, treatment is 15 grams of carbohydrates BG is 40-49 mg/dl, treatment is 30 grams of carbohydrates 15 min later, 2nd BG check, 2nd treatment BG is 60-69 mg/dl, no treatment BG is 50-59 mg/dl, treatment is 15 grams of carbohydrates BG is <50 mg/dl, treatment is participant's preferred oral carbohydrate and not mini-dose glucagon 30 minutes later, 3rd BG check, 3rd treatment BG is >=70 mg/dl, no treatment BG is <70 mg/dl, treatment is participant's preferred oral carbohydrate and not mini-dose glucagon
Measure Participants	15	15
Measure Hypoglycemic Events	48	36
Median (Inter-Quartile Range) [mg/dL]	79	87

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	G-Pen Mini™ (Glucagon Injection), Glucose Tabs
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.02
	Comments
	Method	Mixed Models Analysis
	Comments	Analyzed with generalized linear mixed model with an identity link. Due to violations of normality, rank transformations were used in model.

5. Secondary Outcome

Title	CGM Time in Range, Event Level
Description	Percentage of time 70-180 mg/dL from CGM data, following each hypoglycemic event with starting BG 50-69 mg/dL, during first hour after start of hypoglycemic event
Time Frame	60 Minutes

Outcome Measure Data

Analysis Population Description

A participant had to have sufficient calibrations using study BGM to compare BGM and CGM data to ensure matching dates and times. Event level requirements: 1) initial treatment and dose had to be correct, 2) ≥6 CGM readings within 1 hour after initial treatment, and 3) first CGM glucose after the start of the hypoglycemic event had to be <80 mg/dL

Arm/Group Title	G-Pen Mini™ (Glucagon Injection)	Glucose Tabs
Arm/Group Description	For G-Pen Mini Period: Participants are to check blood glucose (BG) with study meter if continuous glucose monitor (CGM) reads <70 mg/dl or they experience symptoms. Participants instructed to treat using mini-dose glucagon for certain phases/periods when BG is 40 to 69 mg/dl (considered a non-severe hypoglycemic event). G-Pen Mini™ (glucagon injection): 1st BG check, 1st treatment BG is 50-69 mg/dl, treatment is 150 µg of glucagon BG is 40-49 mg/dl, treatment is 300 µg of glucagon 15 min later, 2nd BG check, 2nd treatment BG is 60-69 mg/dl, no treatment BG is 50-59 mg/dl, treatment is 150 µg of glucagon BG is <50 mg/dl, treatment is participant's preferred oral carbohydrate and not mini-dose glucagon 30 minutes later, 3rd BG check, 3rd treatment BG is >=70, no treatment BG is <70 mg/dl, treatment is participant's preferred oral carbohydrate and not mini-dose glucagon	For Glucose Tabs Period: Participants are to check blood glucose (BG) with study meter if continuous glucose meter reads <70 mg/dl or they experience symptoms. Participants instructed to treat using oral glucose tablets for certain phases/periods when BG is 40 to 69 mg/dl (considered a non-severe hypoglycemic event). Glucose Tabs: 1st BG check, 1st treatment: BG is 50-69 mg/dl, treatment is 15 grams of carbohydrates BG is 40-49 mg/dl, treatment is 30 grams of carbohydrates 15 min later, 2nd BG check, 2nd treatment BG is 60-69 mg/dl, no treatment BG is 50-59 mg/dl, treatment is 15 grams of carbohydrates BG is <50 mg/dl, treatment is participant's preferred oral carbohydrate and not mini-dose glucagon 30 minutes later, 3rd BG check, 3rd treatment BG is >=70 mg/dl, no treatment BG is <70 mg/dl, treatment is participant's preferred oral carbohydrate and not mini-dose glucagon
Measure Participants	15	15
Measure Hypoglycemic Events	48	36
Median (Inter-Quartile Range) [percentage of time]	62	67

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	G-Pen Mini™ (Glucagon Injection), Glucose Tabs
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.86
	Comments
	Method	Mixed Models Analysis
	Comments	Analyzed with generalized linear mixed model with an identity link. Due to violations of normality, rank transformations were used in model.

6. Secondary Outcome

Title	CGM Time Below 70 mg/dL, Event Level
Description	Percentage of time <70 mg/dL from CGM data, following each hypoglycemic event with starting BG 50-69 mg/dL, during first hour after start of hypoglycemic event
Time Frame	60 Minutes

Outcome Measure Data

Analysis Population Description

A participant had to have sufficient calibrations using study BGM to compare BGM and CGM data to ensure matching dates and times. Event level requirements: 1) initial treatment and dose had to be correct, 2) ≥6 CGM readings within 1 hour after initial treatment, and 3) first CGM glucose after the start of the hypoglycemic event had to be <80 mg/dL

Arm/Group Title	G-Pen Mini™ (Glucagon Injection)	Glucose Tabs
Arm/Group Description	For G-Pen Mini Period: Participants are to check blood glucose (BG) with study meter if continuous glucose monitor (CGM) reads <70 mg/dl or they experience symptoms. Participants instructed to treat using mini-dose glucagon for certain phases/periods when BG is 40 to 69 mg/dl (considered a non-severe hypoglycemic event). G-Pen Mini™ (glucagon injection): 1st BG check, 1st treatment BG is 50-69 mg/dl, treatment is 150 µg of glucagon BG is 40-49 mg/dl, treatment is 300 µg of glucagon 15 min later, 2nd BG check, 2nd treatment BG is 60-69 mg/dl, no treatment BG is 50-59 mg/dl, treatment is 150 µg of glucagon BG is <50 mg/dl, treatment is participant's preferred oral carbohydrate and not mini-dose glucagon 30 minutes later, 3rd BG check, 3rd treatment BG is >=70, no treatment BG is <70 mg/dl, treatment is participant's preferred oral carbohydrate and not mini-dose glucagon	For Glucose Tabs Period: Participants are to check blood glucose (BG) with study meter if continuous glucose meter reads <70 mg/dl or they experience symptoms. Participants instructed to treat using oral glucose tablets for certain phases/periods when BG is 40 to 69 mg/dl (considered a non-severe hypoglycemic event). Glucose Tabs: 1st BG check, 1st treatment: BG is 50-69 mg/dl, treatment is 15 grams of carbohydrates BG is 40-49 mg/dl, treatment is 30 grams of carbohydrates 15 min later, 2nd BG check, 2nd treatment BG is 60-69 mg/dl, no treatment BG is 50-59 mg/dl, treatment is 15 grams of carbohydrates BG is <50 mg/dl, treatment is participant's preferred oral carbohydrate and not mini-dose glucagon 30 minutes later, 3rd BG check, 3rd treatment BG is >=70 mg/dl, no treatment BG is <70 mg/dl, treatment is participant's preferred oral carbohydrate and not mini-dose glucagon
Measure Participants	15	15
Measure Hypoglycemic Events	48	36
Median (Inter-Quartile Range) [percentage of time]	35	33

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	G-Pen Mini™ (Glucagon Injection), Glucose Tabs
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.95
	Comments
	Method	Mixed Models Analysis
	Comments	Analyzed with generalized linear mixed model with an identity link. Due to violations of normality, rank transformations were used in model.

7. Secondary Outcome

Title	CGM Minimum Glucose, Event Level
Description	Minimum glucose from CGM data, following each hypoglycemic event with starting BG 50-69 mg/dL, during first 2 hours after start of hypoglycemic event
Time Frame	120 Minutes

Outcome Measure Data

Analysis Population Description

A participant had to have sufficient calibrations using study BGM to compare BGM and CGM data to ensure matching dates and times. Event level requirements: 1) initial treatment and dose had to be correct, 2) ≥6 CGM readings within 1 hour after initial treatment, and 3) first CGM glucose after the start of the hypoglycemic event had to be <80 mg/dL

Arm/Group Title	G-Pen Mini™ (Glucagon Injection)	Glucose Tabs
Arm/Group Description	For G-Pen Mini Period: Participants are to check blood glucose (BG) with study meter if continuous glucose monitor (CGM) reads <70 mg/dl or they experience symptoms. Participants instructed to treat using mini-dose glucagon for certain phases/periods when BG is 40 to 69 mg/dl (considered a non-severe hypoglycemic event). G-Pen Mini™ (glucagon injection): 1st BG check, 1st treatment BG is 50-69 mg/dl, treatment is 150 µg of glucagon BG is 40-49 mg/dl, treatment is 300 µg of glucagon 15 min later, 2nd BG check, 2nd treatment BG is 60-69 mg/dl, no treatment BG is 50-59 mg/dl, treatment is 150 µg of glucagon BG is <50 mg/dl, treatment is participant's preferred oral carbohydrate and not mini-dose glucagon 30 minutes later, 3rd BG check, 3rd treatment BG is >=70, no treatment BG is <70 mg/dl, treatment is participant's preferred oral carbohydrate and not mini-dose glucagon	For Glucose Tabs Period: Participants are to check blood glucose (BG) with study meter if continuous glucose meter reads <70 mg/dl or they experience symptoms. Participants instructed to treat using oral glucose tablets for certain phases/periods when BG is 40 to 69 mg/dl (considered a non-severe hypoglycemic event). Glucose Tabs: 1st BG check, 1st treatment: BG is 50-69 mg/dl, treatment is 15 grams of carbohydrates BG is 40-49 mg/dl, treatment is 30 grams of carbohydrates 15 min later, 2nd BG check, 2nd treatment BG is 60-69 mg/dl, no treatment BG is 50-59 mg/dl, treatment is 15 grams of carbohydrates BG is <50 mg/dl, treatment is participant's preferred oral carbohydrate and not mini-dose glucagon 30 minutes later, 3rd BG check, 3rd treatment BG is >=70 mg/dl, no treatment BG is <70 mg/dl, treatment is participant's preferred oral carbohydrate and not mini-dose glucagon
Measure Participants	15	15
Measure Hypoglycemic Events	48	36
Median (Inter-Quartile Range) [mg/dL]	57	56

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	G-Pen Mini™ (Glucagon Injection), Glucose Tabs
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.78
	Comments
	Method	Mixed Models Analysis
	Comments	Analyzed with generalized linear mixed model with an identity link. Due to violations of normality, rank transformations were used in model.

8. Secondary Outcome

Title	CGM Maximum Glucose, Event Level
Description	Maximum glucose from CGM data, following each hypoglycemic event with starting BG 50-69 mg/dL, during first 2 hours after start of hypoglycemic event
Time Frame	120 Minutes

Outcome Measure Data

Analysis Population Description

A participant had to have sufficient calibrations using study BGM to compare BGM and CGM data to ensure matching dates and times. Event level requirements: 1) initial treatment and dose had to be correct, 2) ≥6 CGM readings within 1 hour after initial treatment, and 3) first CGM glucose after the start of the hypoglycemic event had to be <80 mg/dL

Arm/Group Title	G-Pen Mini™ (Glucagon Injection)	Glucose Tabs
Arm/Group Description	For G-Pen Mini Period: Participants are to check blood glucose (BG) with study meter if continuous glucose monitor (CGM) reads <70 mg/dl or they experience symptoms. Participants instructed to treat using mini-dose glucagon for certain phases/periods when BG is 40 to 69 mg/dl (considered a non-severe hypoglycemic event). G-Pen Mini™ (glucagon injection): 1st BG check, 1st treatment BG is 50-69 mg/dl, treatment is 150 µg of glucagon BG is 40-49 mg/dl, treatment is 300 µg of glucagon 15 min later, 2nd BG check, 2nd treatment BG is 60-69 mg/dl, no treatment BG is 50-59 mg/dl, treatment is 150 µg of glucagon BG is <50 mg/dl, treatment is participant's preferred oral carbohydrate and not mini-dose glucagon 30 minutes later, 3rd BG check, 3rd treatment BG is >=70, no treatment BG is <70 mg/dl, treatment is participant's preferred oral carbohydrate and not mini-dose glucagon	For Glucose Tabs Period: Participants are to check blood glucose (BG) with study meter if continuous glucose meter reads <70 mg/dl or they experience symptoms. Participants instructed to treat using oral glucose tablets for certain phases/periods when BG is 40 to 69 mg/dl (considered a non-severe hypoglycemic event). Glucose Tabs: 1st BG check, 1st treatment: BG is 50-69 mg/dl, treatment is 15 grams of carbohydrates BG is 40-49 mg/dl, treatment is 30 grams of carbohydrates 15 min later, 2nd BG check, 2nd treatment BG is 60-69 mg/dl, no treatment BG is 50-59 mg/dl, treatment is 15 grams of carbohydrates BG is <50 mg/dl, treatment is participant's preferred oral carbohydrate and not mini-dose glucagon 30 minutes later, 3rd BG check, 3rd treatment BG is >=70 mg/dl, no treatment BG is <70 mg/dl, treatment is participant's preferred oral carbohydrate and not mini-dose glucagon
Measure Participants	15	15
Measure Hypoglycemic Events	48	36
Median (Inter-Quartile Range) [mg/dL]	122	139

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	G-Pen Mini™ (Glucagon Injection), Glucose Tabs
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.21
	Comments
	Method	Mixed Models Analysis
	Comments	Analyzed with generalized linear mixed model with an identity link. Due to violations of normality, rank transformations were used in model.

9. Secondary Outcome

Title	CGM Mean Glucose, Event Level
Description	Median (IQR) reported for mean glucose from CGM data, following each hypoglycemic event with starting BG 50-69 mg/dL, during first 2 hours after start of hypoglycemic event
Time Frame	120 Minutes

Outcome Measure Data

Analysis Population Description

A participant had to have sufficient calibrations using study BGM to compare BGM and CGM data to ensure matching dates and times. Event level requirements: 1) initial treatment and dose had to be correct, 2) ≥6 CGM readings within 1 hour after initial treatment, and 3) first CGM glucose after the start of the hypoglycemic event had to be <80 mg/dL

Arm/Group Title	G-Pen Mini™ (Glucagon Injection)	Glucose Tabs
Arm/Group Description	For G-Pen Mini Period: Participants are to check blood glucose (BG) with study meter if continuous glucose monitor (CGM) reads <70 mg/dl or they experience symptoms. Participants instructed to treat using mini-dose glucagon for certain phases/periods when BG is 40 to 69 mg/dl (considered a non-severe hypoglycemic event). G-Pen Mini™ (glucagon injection): 1st BG check, 1st treatment BG is 50-69 mg/dl, treatment is 150 µg of glucagon BG is 40-49 mg/dl, treatment is 300 µg of glucagon 15 min later, 2nd BG check, 2nd treatment BG is 60-69 mg/dl, no treatment BG is 50-59 mg/dl, treatment is 150 µg of glucagon BG is <50 mg/dl, treatment is participant's preferred oral carbohydrate and not mini-dose glucagon 30 minutes later, 3rd BG check, 3rd treatment BG is >=70, no treatment BG is <70 mg/dl, treatment is participant's preferred oral carbohydrate and not mini-dose glucagon	For Glucose Tabs Period: Participants are to check blood glucose (BG) with study meter if continuous glucose meter reads <70 mg/dl or they experience symptoms. Participants instructed to treat using oral glucose tablets for certain phases/periods when BG is 40 to 69 mg/dl (considered a non-severe hypoglycemic event). Glucose Tabs: 1st BG check, 1st treatment: BG is 50-69 mg/dl, treatment is 15 grams of carbohydrates BG is 40-49 mg/dl, treatment is 30 grams of carbohydrates 15 min later, 2nd BG check, 2nd treatment BG is 60-69 mg/dl, no treatment BG is 50-59 mg/dl, treatment is 15 grams of carbohydrates BG is <50 mg/dl, treatment is participant's preferred oral carbohydrate and not mini-dose glucagon 30 minutes later, 3rd BG check, 3rd treatment BG is >=70 mg/dl, no treatment BG is <70 mg/dl, treatment is participant's preferred oral carbohydrate and not mini-dose glucagon
Measure Participants	15	15
Measure Hypoglycemic Events	48	36
Median (Inter-Quartile Range) [mg/dL]	95	108

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	G-Pen Mini™ (Glucagon Injection), Glucose Tabs
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.09
	Comments
	Method	Mixed Models Analysis
	Comments	Analyzed with generalized linear mixed model with an identity link. Due to violations of normality, rank transformations were used in model.

10. Secondary Outcome

Title	CGM Time in Range, Event Level
Description	Percentage of time 70-180 mg/dL from CGM data, following each hypoglycemic event with starting BG 50-69 mg/dL, during first 2 hours after start of hypoglycemic event
Time Frame	120 Minutes

Outcome Measure Data

Analysis Population Description

A participant had to have sufficient calibrations using study BGM to compare BGM and CGM data to ensure matching dates and times. Event level requirements: 1) initial treatment and dose had to be correct, 2) ≥6 CGM readings within 1 hour after initial treatment, and 3) first CGM glucose after the start of the hypoglycemic event had to be <80 mg/dL

Arm/Group Title	G-Pen Mini™ (Glucagon Injection)	Glucose Tabs
Arm/Group Description	For G-Pen Mini Period: Participants are to check blood glucose (BG) with study meter if continuous glucose monitor (CGM) reads <70 mg/dl or they experience symptoms. Participants instructed to treat using mini-dose glucagon for certain phases/periods when BG is 40 to 69 mg/dl (considered a non-severe hypoglycemic event). G-Pen Mini™ (glucagon injection): 1st BG check, 1st treatment BG is 50-69 mg/dl, treatment is 150 µg of glucagon BG is 40-49 mg/dl, treatment is 300 µg of glucagon 15 min later, 2nd BG check, 2nd treatment BG is 60-69 mg/dl, no treatment BG is 50-59 mg/dl, treatment is 150 µg of glucagon BG is <50 mg/dl, treatment is participant's preferred oral carbohydrate and not mini-dose glucagon 30 minutes later, 3rd BG check, 3rd treatment BG is >=70, no treatment BG is <70 mg/dl, treatment is participant's preferred oral carbohydrate and not mini-dose glucagon	For Glucose Tabs Period: Participants are to check blood glucose (BG) with study meter if continuous glucose meter reads <70 mg/dl or they experience symptoms. Participants instructed to treat using oral glucose tablets for certain phases/periods when BG is 40 to 69 mg/dl (considered a non-severe hypoglycemic event). Glucose Tabs: 1st BG check, 1st treatment: BG is 50-69 mg/dl, treatment is 15 grams of carbohydrates BG is 40-49 mg/dl, treatment is 30 grams of carbohydrates 15 min later, 2nd BG check, 2nd treatment BG is 60-69 mg/dl, no treatment BG is 50-59 mg/dl, treatment is 15 grams of carbohydrates BG is <50 mg/dl, treatment is participant's preferred oral carbohydrate and not mini-dose glucagon 30 minutes later, 3rd BG check, 3rd treatment BG is >=70 mg/dl, no treatment BG is <70 mg/dl, treatment is participant's preferred oral carbohydrate and not mini-dose glucagon
Measure Participants	15	15
Measure Hypoglycemic Events	48	36
Median (Inter-Quartile Range) [percentage of time]	79	79

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	G-Pen Mini™ (Glucagon Injection), Glucose Tabs
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.49
	Comments
	Method	Mixed Models Analysis
	Comments	Analyzed with generalized linear mixed model with an identity link. Due to violations of normality, rank transformations were used in model.

11. Secondary Outcome

Title	CGM Time Below 70 mg/dL
Description	Percentage of time <70 mg/dL from CGM data, following each hypoglycemic event with starting BG 50-69 mg/dL, during first 2 hours after start of hypoglycemic event
Time Frame	120 Minutes

Outcome Measure Data

Analysis Population Description

A participant had to have sufficient calibrations using study BGM to compare BGM and CGM data to ensure matching dates and times. Event level requirements: 1) initial treatment and dose had to be correct, 2) ≥6 CGM readings within 1 hour after initial treatment, and 3) first CGM glucose after the start of the hypoglycemic event had to be <80 mg/dL

Arm/Group Title	G-Pen Mini™ (Glucagon Injection)	Glucose Tabs
Arm/Group Description	For G-Pen Mini Period: Participants are to check blood glucose (BG) with study meter if continuous glucose monitor (CGM) reads <70 mg/dl or they experience symptoms. Participants instructed to treat using mini-dose glucagon for certain phases/periods when BG is 40 to 69 mg/dl (considered a non-severe hypoglycemic event). G-Pen Mini™ (glucagon injection): 1st BG check, 1st treatment BG is 50-69 mg/dl, treatment is 150 µg of glucagon BG is 40-49 mg/dl, treatment is 300 µg of glucagon 15 min later, 2nd BG check, 2nd treatment BG is 60-69 mg/dl, no treatment BG is 50-59 mg/dl, treatment is 150 µg of glucagon BG is <50 mg/dl, treatment is participant's preferred oral carbohydrate and not mini-dose glucagon 30 minutes later, 3rd BG check, 3rd treatment BG is >=70, no treatment BG is <70 mg/dl, treatment is participant's preferred oral carbohydrate and not mini-dose glucagon	For Glucose Tabs Period: Participants are to check blood glucose (BG) with study meter if continuous glucose meter reads <70 mg/dl or they experience symptoms. Participants instructed to treat using oral glucose tablets for certain phases/periods when BG is 40 to 69 mg/dl (considered a non-severe hypoglycemic event). Glucose Tabs: 1st BG check, 1st treatment: BG is 50-69 mg/dl, treatment is 15 grams of carbohydrates BG is 40-49 mg/dl, treatment is 30 grams of carbohydrates 15 min later, 2nd BG check, 2nd treatment BG is 60-69 mg/dl, no treatment BG is 50-59 mg/dl, treatment is 15 grams of carbohydrates BG is <50 mg/dl, treatment is participant's preferred oral carbohydrate and not mini-dose glucagon 30 minutes later, 3rd BG check, 3rd treatment BG is >=70 mg/dl, no treatment BG is <70 mg/dl, treatment is participant's preferred oral carbohydrate and not mini-dose glucagon
Measure Participants	15	15
Measure Hypoglycemic Events	48	36
Median (Inter-Quartile Range) [percentage of time]	20	19

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	G-Pen Mini™ (Glucagon Injection), Glucose Tabs
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.63
	Comments
	Method	Mixed Models Analysis
	Comments	Analyzed with generalized linear mixed model with an identity link. Due to violations of normality, rank transformations were used in model.

12. Secondary Outcome

Title	CGM Mean Glucose
Description	Median (IQR) reported for mean glucose from CGM data computed over entire 3 weeks of treatment period
Time Frame	3 weeks

Outcome Measure Data

Analysis Population Description

Limited to participants who had at least 72 hours of CGM data during each period

Arm/Group Title	G-Pen Mini™ (Glucagon Injection)	Glucose Tabs
Arm/Group Description	For G-Pen Mini Period: Participants are to check blood glucose (BG) with study meter if continuous glucose monitor (CGM) reads <70 mg/dl or they experience symptoms. Participants instructed to treat using mini-dose glucagon for certain phases/periods when BG is 40 to 69 mg/dl (considered a non-severe hypoglycemic event). G-Pen Mini™ (glucagon injection): 1st BG check, 1st treatment BG is 50-69 mg/dl, treatment is 150 µg of glucagon BG is 40-49 mg/dl, treatment is 300 µg of glucagon 15 min later, 2nd BG check, 2nd treatment BG is 60-69 mg/dl, no treatment BG is 50-59 mg/dl, treatment is 150 µg of glucagon BG is <50 mg/dl, treatment is participant's preferred oral carbohydrate and not mini-dose glucagon 30 minutes later, 3rd BG check, 3rd treatment BG is >=70, no treatment BG is <70 mg/dl, treatment is participant's preferred oral carbohydrate and not mini-dose glucagon	For Glucose Tabs Period: Participants are to check blood glucose (BG) with study meter if continuous glucose meter reads <70 mg/dl or they experience symptoms. Participants instructed to treat using oral glucose tablets for certain phases/periods when BG is 40 to 69 mg/dl (considered a non-severe hypoglycemic event). Glucose Tabs: 1st BG check, 1st treatment: BG is 50-69 mg/dl, treatment is 15 grams of carbohydrates BG is 40-49 mg/dl, treatment is 30 grams of carbohydrates 15 min later, 2nd BG check, 2nd treatment BG is 60-69 mg/dl, no treatment BG is 50-59 mg/dl, treatment is 15 grams of carbohydrates BG is <50 mg/dl, treatment is participant's preferred oral carbohydrate and not mini-dose glucagon 30 minutes later, 3rd BG check, 3rd treatment BG is >=70 mg/dl, no treatment BG is <70 mg/dl, treatment is participant's preferred oral carbohydrate and not mini-dose glucagon
Measure Participants	15	15
Median (Inter-Quartile Range) [mg/dL]	143	149

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	G-Pen Mini™ (Glucagon Injection), Glucose Tabs
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.41
	Comments
	Method	Mixed Models Analysis
	Comments	Analyzed with generalized linear mixed model with an identity link. Due to violations of normality, rank transformations were used in model.

13. Secondary Outcome

Title	CGM Time in Range
Description	Percentage of time 70-180 mg/dL from CGM data computed over entire 3 weeks of treatment period
Time Frame	3 weeks

Outcome Measure Data

Analysis Population Description

Limited to participants who had at least 72 hours of CGM data during each period

Arm/Group Title	G-Pen Mini™ (Glucagon Injection)	Glucose Tabs
Arm/Group Description	For G-Pen Mini Period: Participants are to check blood glucose (BG) with study meter if continuous glucose monitor (CGM) reads <70 mg/dl or they experience symptoms. Participants instructed to treat using mini-dose glucagon for certain phases/periods when BG is 40 to 69 mg/dl (considered a non-severe hypoglycemic event). G-Pen Mini™ (glucagon injection): 1st BG check, 1st treatment BG is 50-69 mg/dl, treatment is 150 µg of glucagon BG is 40-49 mg/dl, treatment is 300 µg of glucagon 15 min later, 2nd BG check, 2nd treatment BG is 60-69 mg/dl, no treatment BG is 50-59 mg/dl, treatment is 150 µg of glucagon BG is <50 mg/dl, treatment is participant's preferred oral carbohydrate and not mini-dose glucagon 30 minutes later, 3rd BG check, 3rd treatment BG is >=70, no treatment BG is <70 mg/dl, treatment is participant's preferred oral carbohydrate and not mini-dose glucagon	For Glucose Tabs Period: Participants are to check blood glucose (BG) with study meter if continuous glucose meter reads <70 mg/dl or they experience symptoms. Participants instructed to treat using oral glucose tablets for certain phases/periods when BG is 40 to 69 mg/dl (considered a non-severe hypoglycemic event). Glucose Tabs: 1st BG check, 1st treatment: BG is 50-69 mg/dl, treatment is 15 grams of carbohydrates BG is 40-49 mg/dl, treatment is 30 grams of carbohydrates 15 min later, 2nd BG check, 2nd treatment BG is 60-69 mg/dl, no treatment BG is 50-59 mg/dl, treatment is 15 grams of carbohydrates BG is <50 mg/dl, treatment is participant's preferred oral carbohydrate and not mini-dose glucagon 30 minutes later, 3rd BG check, 3rd treatment BG is >=70 mg/dl, no treatment BG is <70 mg/dl, treatment is participant's preferred oral carbohydrate and not mini-dose glucagon
Measure Participants	15	15
Median (Inter-Quartile Range) [percentage of time]	71	71

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	G-Pen Mini™ (Glucagon Injection), Glucose Tabs
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.80
	Comments
	Method	Mixed Models Analysis
	Comments	Analyzed with generalized linear mixed model with an identity link. Due to violations of normality, rank transformations were used in model.

14. Secondary Outcome

Title	CGM Time Below 70
Description	Percentage of time <70 mg/dL from CGM data computed over entire 3 weeks of treatment period
Time Frame	3 weeks

Outcome Measure Data

Analysis Population Description

Limited to participants who had at least 72 hours of CGM data during each period

Arm/Group Title	G-Pen Mini™ (Glucagon Injection)	Glucose Tabs
Arm/Group Description	For G-Pen Mini Period: Participants are to check blood glucose (BG) with study meter if continuous glucose monitor (CGM) reads <70 mg/dl or they experience symptoms. Participants instructed to treat using mini-dose glucagon for certain phases/periods when BG is 40 to 69 mg/dl (considered a non-severe hypoglycemic event). G-Pen Mini™ (glucagon injection): 1st BG check, 1st treatment BG is 50-69 mg/dl, treatment is 150 µg of glucagon BG is 40-49 mg/dl, treatment is 300 µg of glucagon 15 min later, 2nd BG check, 2nd treatment BG is 60-69 mg/dl, no treatment BG is 50-59 mg/dl, treatment is 150 µg of glucagon BG is <50 mg/dl, treatment is participant's preferred oral carbohydrate and not mini-dose glucagon 30 minutes later, 3rd BG check, 3rd treatment BG is >=70, no treatment BG is <70 mg/dl, treatment is participant's preferred oral carbohydrate and not mini-dose glucagon	For Glucose Tabs Period: Participants are to check blood glucose (BG) with study meter if continuous glucose meter reads <70 mg/dl or they experience symptoms. Participants instructed to treat using oral glucose tablets for certain phases/periods when BG is 40 to 69 mg/dl (considered a non-severe hypoglycemic event). Glucose Tabs: 1st BG check, 1st treatment: BG is 50-69 mg/dl, treatment is 15 grams of carbohydrates BG is 40-49 mg/dl, treatment is 30 grams of carbohydrates 15 min later, 2nd BG check, 2nd treatment BG is 60-69 mg/dl, no treatment BG is 50-59 mg/dl, treatment is 15 grams of carbohydrates BG is <50 mg/dl, treatment is participant's preferred oral carbohydrate and not mini-dose glucagon 30 minutes later, 3rd BG check, 3rd treatment BG is >=70 mg/dl, no treatment BG is <70 mg/dl, treatment is participant's preferred oral carbohydrate and not mini-dose glucagon
Measure Participants	15	15
Median (Inter-Quartile Range) [percentage of time]	5	4

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	G-Pen Mini™ (Glucagon Injection), Glucose Tabs
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.13
	Comments
	Method	Mixed Models Analysis
	Comments	Analyzed with generalized linear mixed model with an identity link. Due to violations of normality, rank transformations were used in model.

15. Secondary Outcome

Title	CGM Coefficient of Variation
Description	Coefficient of Variation from CGM data computed over entire 3 weeks of treatment period
Time Frame	3 weeks

Outcome Measure Data

Analysis Population Description

Limited to participants who had at least 72 hours of CGM data during each period

Arm/Group Title	G-Pen Mini™ (Glucagon Injection)	Glucose Tabs
Arm/Group Description	For G-Pen Mini Period: Participants are to check blood glucose (BG) with study meter if continuous glucose monitor (CGM) reads <70 mg/dl or they experience symptoms. Participants instructed to treat using mini-dose glucagon for certain phases/periods when BG is 40 to 69 mg/dl (considered a non-severe hypoglycemic event). G-Pen Mini™ (glucagon injection): 1st BG check, 1st treatment BG is 50-69 mg/dl, treatment is 150 µg of glucagon BG is 40-49 mg/dl, treatment is 300 µg of glucagon 15 min later, 2nd BG check, 2nd treatment BG is 60-69 mg/dl, no treatment BG is 50-59 mg/dl, treatment is 150 µg of glucagon BG is <50 mg/dl, treatment is participant's preferred oral carbohydrate and not mini-dose glucagon 30 minutes later, 3rd BG check, 3rd treatment BG is >=70, no treatment BG is <70 mg/dl, treatment is participant's preferred oral carbohydrate and not mini-dose glucagon	For Glucose Tabs Period: Participants are to check blood glucose (BG) with study meter if continuous glucose meter reads <70 mg/dl or they experience symptoms. Participants instructed to treat using oral glucose tablets for certain phases/periods when BG is 40 to 69 mg/dl (considered a non-severe hypoglycemic event). Glucose Tabs: 1st BG check, 1st treatment: BG is 50-69 mg/dl, treatment is 15 grams of carbohydrates BG is 40-49 mg/dl, treatment is 30 grams of carbohydrates 15 min later, 2nd BG check, 2nd treatment BG is 60-69 mg/dl, no treatment BG is 50-59 mg/dl, treatment is 15 grams of carbohydrates BG is <50 mg/dl, treatment is participant's preferred oral carbohydrate and not mini-dose glucagon 30 minutes later, 3rd BG check, 3rd treatment BG is >=70 mg/dl, no treatment BG is <70 mg/dl, treatment is participant's preferred oral carbohydrate and not mini-dose glucagon
Measure Participants	15	15
Median (Inter-Quartile Range) [percentage coefficient of variation]	35	36

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	G-Pen Mini™ (Glucagon Injection), Glucose Tabs
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.70
	Comments
	Method	Mixed Models Analysis
	Comments	Analyzed with generalized linear mixed model with an identity link. Due to violations of normality, rank transformations were used in model.

16. Post-Hoc Outcome

Title	Clinical Grading - Limited to Events in Primary Analysis
Description	2 graders, blinded to treatment arm, independently graded each hypoglycemic event as a clinical failure or success based on all available BG concentrations within 1 hour of initial treatment. All BG values, along with corresponding time elapsed since treatment, were reviewed to determine whether the response would be considered a treatment success, in a clinical setting. There were no specific cut points; rather than basing the success criteria on whether the BG was above specific cutpoints by specific times, the grader decided whether the event would be considered a success in a clinical setting (i.e. if the BG increased after treatment and reached and maintained a satisfactory level after the treatment). The graders to achieve a consensus grading adjudicated discordant gradings (6% of events). The number of events graded as a treatment success were reported out of the total number of hypoglycemic events, for each treatment arm.
Time Frame	60 minutes

Outcome Measure Data

Analysis Population Description

Analysis was limited to hypoglycemic events included in the primary analysis. 3 hypoglycemic events were deemed Indeterminate by the graders during the glucagon period.

Arm/Group Title	G-Pen Mini™ (Glucagon Injection)	Glucose Tabs
Arm/Group Description	For G-Pen Mini Period: Participants are to check blood glucose (BG) with study meter if continuous glucose monitor (CGM) reads <70 mg/dl or they experience symptoms. Participants instructed to treat using mini-dose glucagon for certain phases/periods when BG is 40 to 69 mg/dl (considered a non-severe hypoglycemic event). G-Pen Mini™ (glucagon injection): 1st BG check, 1st treatment BG is 50-69 mg/dl, treatment is 150 µg of glucagon BG is 40-49 mg/dl, treatment is 300 µg of glucagon 15 min later, 2nd BG check, 2nd treatment BG is 60-69 mg/dl, no treatment BG is 50-59 mg/dl, treatment is 150 µg of glucagon BG is <50 mg/dl, treatment is participant's preferred oral carbohydrate and not mini-dose glucagon 30 minutes later, 3rd BG check, 3rd treatment BG is >=70, no treatment BG is <70 mg/dl, treatment is participant's preferred oral carbohydrate and not mini-dose glucagon	For Glucose Tabs Period: Participants are to check blood glucose (BG) with study meter if continuous glucose meter reads <70 mg/dl or they experience symptoms. Participants instructed to treat using oral glucose tablets for certain phases/periods when BG is 40 to 69 mg/dl (considered a non-severe hypoglycemic event). Glucose Tabs: 1st BG check, 1st treatment: BG is 50-69 mg/dl, treatment is 15 grams of carbohydrates BG is 40-49 mg/dl, treatment is 30 grams of carbohydrates 15 min later, 2nd BG check, 2nd treatment BG is 60-69 mg/dl, no treatment BG is 50-59 mg/dl, treatment is 15 grams of carbohydrates BG is <50 mg/dl, treatment is participant's preferred oral carbohydrate and not mini-dose glucagon 30 minutes later, 3rd BG check, 3rd treatment BG is >=70 mg/dl, no treatment BG is <70 mg/dl, treatment is participant's preferred oral carbohydrate and not mini-dose glucagon
Measure Participants	16	16
Measure Hypoglycemic Events	59	56
Count of Units [Hypoglycemic Events]	57	54

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	G-Pen Mini™ (Glucagon Injection), Glucose Tabs
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.93
	Comments	Proportions of successes in each arm were compared using a generalized linear mixed model with a logistic link function, random participant effect to account for correlated data from some pts having multiple events, and adjustment for baseline BG.
	Method	Mixed Models Analysis
	Comments

17. Post-Hoc Outcome

Title	Clinical Grading - Initial and 15-min Treatment Correct
Description	2 graders, blinded to treatment arm, independently graded each hypoglycemic event as a clinical failure or success based on all available BG concentrations within 1 hour of initial treatment. All BG values, along with corresponding time elapsed since treatment, were reviewed to determine whether the response would be considered a treatment success, in a clinical setting. There were no specific cut points; rather than basing the success criteria on whether the BG was above specific cutpoints by specific times, the grader decided whether the event would be considered a success in a clinical setting (i.e. if the BG increased after treatment and reached and maintained a satisfactory level after the treatment). The graders to achieve a consensus grading adjudicated discordant gradings (6% of events). The number of events graded as a treatment success were reported out of the total number of hypoglycemic events, for each treatment arm.
Time Frame	60 minutes

Outcome Measure Data

Analysis Population Description

Analysis was limited to hypoglycemic events where Initial and 15-min Treatment were correct. 4 hypoglycemic events were deemed Indeterminate by the graders during the glucagon period.

Arm/Group Title	G-Pen Mini™ (Glucagon Injection)	Glucose Tabs
Arm/Group Description	For G-Pen Mini Period: Participants are to check blood glucose (BG) with study meter if continuous glucose monitor (CGM) reads <70 mg/dl or they experience symptoms. Participants instructed to treat using mini-dose glucagon for certain phases/periods when BG is 40 to 69 mg/dl (considered a non-severe hypoglycemic event). G-Pen Mini™ (glucagon injection): 1st BG check, 1st treatment BG is 50-69 mg/dl, treatment is 150 µg of glucagon BG is 40-49 mg/dl, treatment is 300 µg of glucagon 15 min later, 2nd BG check, 2nd treatment BG is 60-69 mg/dl, no treatment BG is 50-59 mg/dl, treatment is 150 µg of glucagon BG is <50 mg/dl, treatment is participant's preferred oral carbohydrate and not mini-dose glucagon 30 minutes later, 3rd BG check, 3rd treatment BG is >=70, no treatment BG is <70 mg/dl, treatment is participant's preferred oral carbohydrate and not mini-dose glucagon	For Glucose Tabs Period: Participants are to check blood glucose (BG) with study meter if continuous glucose meter reads <70 mg/dl or they experience symptoms. Participants instructed to treat using oral glucose tablets for certain phases/periods when BG is 40 to 69 mg/dl (considered a non-severe hypoglycemic event). Glucose Tabs: 1st BG check, 1st treatment: BG is 50-69 mg/dl, treatment is 15 grams of carbohydrates BG is 40-49 mg/dl, treatment is 30 grams of carbohydrates 15 min later, 2nd BG check, 2nd treatment BG is 60-69 mg/dl, no treatment BG is 50-59 mg/dl, treatment is 15 grams of carbohydrates BG is <50 mg/dl, treatment is participant's preferred oral carbohydrate and not mini-dose glucagon 30 minutes later, 3rd BG check, 3rd treatment BG is >=70 mg/dl, no treatment BG is <70 mg/dl, treatment is participant's preferred oral carbohydrate and not mini-dose glucagon
Measure Participants	16	16
Measure Hypoglycemic Events	69	67
Count of Units [Hypoglycemic Events]	66	63

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	G-Pen Mini™ (Glucagon Injection), Glucose Tabs
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.66
	Comments	Proportions of successes in each arm were compared using a generalized linear mixed model with a logistic link function, random participant effect to account for correlated data from some pts having multiple events, and adjustment for baseline BG.
	Method	Mixed Models Analysis
	Comments

18. Post-Hoc Outcome

Title	Clinical Grading - Initial Treatment Correct
Description	2 graders, blinded to treatment arm, independently graded each hypoglycemic event as a clinical failure or success based on all available BG concentrations within 1 hour of initial treatment. All BG values, along with corresponding time elapsed since treatment, were reviewed to determine whether the response would be considered a treatment success, in a clinical setting. There were no specific cut points; rather than basing the success criteria on whether the BG was above specific cutpoints by specific times, the grader decided whether the event would be considered a success in a clinical setting (i.e. if the BG increased after treatment and reached and maintained a satisfactory level after the treatment). The graders to achieve a consensus grading adjudicated discordant gradings (6% of events). The number of events graded as a treatment success were reported out of the total number of hypoglycemic events, for each treatment arm.
Time Frame	60 minutes

Outcome Measure Data

Analysis Population Description

This analysis included all hypoglycemic events in which the initial treatment and dose were correct, irrespective of the timing of the BG measurements. 8 hypoglycemic events were deemed Indeterminate by the graders during the glucagon period and 4 during the glucose tabs period.

Arm/Group Title	G-Pen Mini™ (Glucagon Injection)	Glucose Tabs
Arm/Group Description	For G-Pen Mini Period: Participants are to check blood glucose (BG) with study meter if continuous glucose monitor (CGM) reads <70 mg/dl or they experience symptoms. Participants instructed to treat using mini-dose glucagon for certain phases/periods when BG is 40 to 69 mg/dl (considered a non-severe hypoglycemic event). G-Pen Mini™ (glucagon injection): 1st BG check, 1st treatment BG is 50-69 mg/dl, treatment is 150 µg of glucagon BG is 40-49 mg/dl, treatment is 300 µg of glucagon 15 min later, 2nd BG check, 2nd treatment BG is 60-69 mg/dl, no treatment BG is 50-59 mg/dl, treatment is 150 µg of glucagon BG is <50 mg/dl, treatment is participant's preferred oral carbohydrate and not mini-dose glucagon 30 minutes later, 3rd BG check, 3rd treatment BG is >=70, no treatment BG is <70 mg/dl, treatment is participant's preferred oral carbohydrate and not mini-dose glucagon	For Glucose Tabs Period: Participants are to check blood glucose (BG) with study meter if continuous glucose meter reads <70 mg/dl or they experience symptoms. Participants instructed to treat using oral glucose tablets for certain phases/periods when BG is 40 to 69 mg/dl (considered a non-severe hypoglycemic event). Glucose Tabs: 1st BG check, 1st treatment: BG is 50-69 mg/dl, treatment is 15 grams of carbohydrates BG is 40-49 mg/dl, treatment is 30 grams of carbohydrates 15 min later, 2nd BG check, 2nd treatment BG is 60-69 mg/dl, no treatment BG is 50-59 mg/dl, treatment is 15 grams of carbohydrates BG is <50 mg/dl, treatment is participant's preferred oral carbohydrate and not mini-dose glucagon 30 minutes later, 3rd BG check, 3rd treatment BG is >=70 mg/dl, no treatment BG is <70 mg/dl, treatment is participant's preferred oral carbohydrate and not mini-dose glucagon
Measure Participants	16	16
Measure Hypoglycemic Events	95	92
Count of Units [Hypoglycemic Events]	84	88

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	G-Pen Mini™ (Glucagon Injection), Glucose Tabs
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.08
	Comments	Proportions of successes in each arm were compared using a generalized linear mixed model with a logistic link function, random participant effect to account for correlated data from some pts having multiple events, and adjustment for baseline BG.
	Method	Mixed Models Analysis
	Comments

Adverse Events

Time Frame	Adverse events were collected through study completion, an average of 12 weeks.
Arm/Group Title	G-Pen Mini™ (Glucagon Injection)		Glucose Tabs
Arm/Group Description	Participants treat non-severe hypoglycemic events with glucagon.		Participants treat non-severe hypoglycemic events with glucose tabs.
All Cause Mortality
	G-Pen Mini™ (Glucagon Injection)		Glucose Tabs
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/20 (0%)		0/20 (0%)
Serious Adverse Events
	G-Pen Mini™ (Glucagon Injection)		Glucose Tabs
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/20 (0%)		0/20 (0%)
Other (Not Including Serious) Adverse Events
	G-Pen Mini™ (Glucagon Injection)		Glucose Tabs
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/20 (10%)		1/20 (5%)
Pregnancy, puerperium and perinatal conditions
Unintended Pregnancy	1/20 (5%)	1	0/20 (0%)	0
Respiratory, thoracic and mediastinal disorders
Upper Respiratory Infection	1/20 (5%)	1	0/20 (0%)	0
Streptococcal Sore Throat	1/20 (5%)	1	1/20 (5%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.