Treatment Of Severe Hypoglycemia Research Articles

Hypoglycaemia Among Diabetes Patients: A Preventive Approach

Hypoglycaemia is a low blood glucose concentration and an indicator of diabetes mellitus, and are associated with physical and psychological morbidity. It is a common, potentially avoidable consequence of diabetes treatment, and a major barrier to better metabolic control in diabetes. It is due to overtreatment of diabetes patients with insulin or sulfonylureas or glinides or also consumption of too little food or unplanned excessive exercise or physical activity. It is the acute complication of diabetes and is associated with considerable morbidity and mortality. It is important of the early recognition, treatment, and prevention of hypoglycaemia. Immediate treatment of severe hypoglycaemia is needed to avoid life threatening complications of the diabetic patients. In this study an attempt has been taken to discuss the aspects of hypoglycaemia of diabetes mellitus patients.

Severe Hypoglycemia and the Use of Glucagon Rescue Agents: An Observational Survey in Adults With Type 1 Diabetes.

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.

383-P: Clinical Practice Gap Analysis of Severe Hypoglycemia Assessment and Treatment in Patients with Diabetes

Introduction: Understanding clinical practice gaps in the assessment and treatment of severe hypoglycemia in patients with diabetes can inform development of tools to improve physician practices. Methods: A survey instrument of 25 multiple choice, knowledge- and case-based questions allowed participants to assess their knowledge, attitudes, and confidence with regard to severe hypoglycemia. The survey was available online to physicians across the globe without monetary compensation or charge. Respondent confidentiality was maintained and responses were de-identified and aggregated prior to analyses. Initial data collection occurred from May 4, 2021, to July 12, 2021. Results: In total, 64 diabetologists/endocrinologists (D/Es) and 187 primary care physicians (PCPs) completed the full assessment within the data collection period. When asked how many of their patients with diabetes have a prescription for glucagon, 88% of D/Es estimated <50% (and 69% estimated <20%) , 93% of PCPs estimated <50% (and 87% estimated <20%) . Conclusion: This educational research on assessment of physicians’ clinical practices yielded important insights into clinical gaps related to assessment and treatment of severe hypoglycemia in patients with diabetes. Further studies are planned to assess the effect of medical education on decreasing these clinical practice gaps. Disclosure A.Larkin: None. A.Le: None. J.Schrand: None. Funding Developed through independent educational grant from Xeris Pharmaceuticals

People With Diabetes and Caregivers Prefer Rescue Glucagon Treatment With a Wider Storage Temperature Range and a Nasal Administration, When Efficacy is Similar: A Discrete Choice Experiment in Spain.

Conventional injectable glucagon (IG) and nasal glucagon (NG), both having similar efficacy, are two options for the emergency treatment of severe hypoglycemia in Spain. This study elicited the effect of changes in key attributes on preferences for NG and IG medication profiles of people with diabetes and caregivers in Spain. The relative attribute importance (RAI) that participants placed on glucagon preparation, preparation and administration time, delivery method, recovery time, device size, storage temperature, and headache risk was estimated from an online discrete choice experiment. In addition, patients and caregivers were presented with NG and IG profiles that included rates of successful administration; the proportion of participants choosing each profile was summarized. The analysis included 276 adults with diabetes (65% type 1) and 270 caregivers (49% type 1). Overall mean age was 40 years; 51% were female. The most important attributes were storage temperature (RAI [95% confidence interval] = 27.3% [22.9-32.2]) and delivery method (17.4% [13.1-21.9]). Headache risk (16.2% [11.8-20.7]), time to prepare and administer (14.5% [10.1-18.8]), glucagon preparation (11.4% [6.8-15.8]), recovery time (8.9% [4.3-13.3]), and device size (4.3% [0.3-8.8]) were also relevant. When comparing medication profiles, significantly more participants (78%) preferred NG over IG profiles (P < .001). Adults with diabetes and caregivers prefer a glucagon treatment with a higher rate of successful administration, wider storage temperature, and nasal delivery method, when efficacy is similar. Participants favored NG over conventional IG as a rescue medication for severe hypoglycemia. This information may help decision-making by payers and treatment discussions between health care professionals and patients.

Dasiglucagon demonstrates reduced costs in the treatment of severe hypoglycemia in a budget impact model.

BACKGROUND: Approximately 7.3 million people with type 1 or type 2 diabetes (T1D/T2D) are treated with insulin, placing them at higher risk of severe hypoglycemia (SH). SH requires assistance of another individual and often necessitates the prompt administration of intravenous glucose, injectable glucagon, or both. Untreated, SH can progress to unconsciousness, seizures, coma, or death. Before 2018, all glucagon rescue treatments required reconstitution. The complexity of reconstitution is often a barrier to successful administration during a severe hypoglycemic event. Studies suggest successful administration of glucagon emergency kits range from 6%-56% of the time. Second-generation glucagon treatments and glucagon analogs do not require reconstitution and have caregiver administration success rates ranging from 94%-100%. Dasiglucagon is a glucagon analog administered via autoinjector or prefilled syringe and has been shown to result in rapid hypoglycemia recovery. Moreover, the autoinjector can be administered successfully 94% of the time by trained caregivers. Previous evaluation of costs in budget impact models (BIMs) demonstrated the potential for second-generation glucagon treatments to reduce the cost of SH events (SHEs). The current model expands on those findings with a treatment pathway and accompanying assumptions reflecting important aspects of real-world SHE treatment. OBJECTIVE: To evaluate the economic impact of dasiglucagon compared with available glucagon treatments for SHE management, considering direct cost of treatment and health care resource utilization. METHODS: A 1-year BIM with a hypothetical US commercial health plan of 1 million lives was developed with a target population of individuals with diabetes at risk of SHE. The treatment pathway model included initial and secondary treatment attempts, treatment administration success and failure, plasma glucose (PG) recovery within 15 minutes, emergency medical services, emergency department (ED) visits, and hospitalizations. A 1-way sensitivity analysis was conducted to assess the sensitivity of the model to changes in parameter values. RESULTS: In a 1 million-covered lives population, it was estimated that 12,006 SHEs would occur annually. The higher rate of initial treatment success and PG recovery within 15 minutes associated with dasiglucagon treatment resulted in lower total health care costs. Total SHE treatment costs with dasiglucagon were estimated at $13.4 million, compared with $16.7 million for injectable native glucagon, $20.7 million for nasal glucagon, $35.3 million for reconstituted glucagon, and $43.8 million for untreated individuals. Compared with untreated people, the number needed to treat (NNT) with dasiglucagon was 6 individuals to avoid 1 hospitalization. NNT for this same comparison was 59 for injectable native glucagon and 27 for nasal glucagon. CONCLUSIONS: Treatment of SH with dasiglucagon decreased total direct medical costs by reducing health care resource utilization (emergency calls, emergency transports, ED visits, and hospitalizations) and accompanying costs associated with the treatment of SH. DISCLOSURES: This research was funded by Zealand Pharma. Bromley, Hinahara, and Goss are employed by Boston Healthcare Associates, Inc., which received funding from Zealand Pharma for development of the health economic model and the manuscript. Kendall and Hammer are employed by Zealand Pharma. Weinzimer has received consulting fees from Zealand Pharma.

New Fast Acting Glucagon for Recovery from Hypoglycemia, a Life-Threatening Situation: Nasal Powder and Injected Stable Solutions.

The goal of diabetes care is to achieve and maintain good glycemic control over time, so as to prevent or delay the development of micro- and macrovascular complications in type 1 (T1D) and type 2 diabetes (T2D). However, numerous barriers hinder the achievement of this goal, first of all the frequent episodes of hypoglycemia typical in patients treated with insulin as T1D patients, or sulphonylureas as T2D patients. The prevention strategy and treatment of hypoglycemia are important for the well-being of patients with diabetes. Hypoglycemia is strongly associated with an increased risk of cardiovascular disease in diabetic patients, due probably to the release of inflammatory markers and prothrombotic effects triggered by hypoglycemia. Treatment of hypoglycemia is traditionally based on administration of carbohydrates or of glucagon via intramuscular (IM) or subcutaneous injection (SC). The injection of traditional glucagon is cumbersome, such that glucagon is an under-utilized drug. In 1983, it was shown for the first time that intranasal (IN) glucagon increases blood glucose levels in healthy volunteers, and in 1989–1992 that IN glucagon is similar to IM glucagon in resolving hypoglycemia in normal volunteers and in patients with diabetes, both adults and children. IN glucagon was developed in 2010 and continued in 2015; in 2019 IN glucagon obtained approval in the US, Canada, and Europe for severe hypoglycemia in children and adults. In the 2010s, two ready-to-use injectable formulations, a stable non-aqueous glucagon solution and the glucagon analog dasiglucagon, were developed, showing an efficacy similar to traditional glucagon, and approved in the US in 2020 and in 2021, respectively, for severe hypoglycemia in adults and in children. Fast-acting glucagon (nasal administration and injected solutions) appears to represent a major breakthrough in the treatment of severe hypoglycemia in insulin-treated patients with diabetes, both adults and children. It is anticipated that the availability of fast-acting glucagon will expand the use of glucagon, improve overall metabolic control, and prevent hypoglycemia-related complications, in particular cardiovascular complications and cognitive impairment.

U.S. Survey Investigating Gaps between Patients and Specialists in the Treatment of Severe Hypoglycemia and Impressions of the Ease-of-Use of Liquid-Stable Glucagon for Subcutaneous Injection

Severe hypoglycemia is an emergency condition where very low blood sugar may lead to confusion, seizure, unconsciousness, and if left untreated, death. It has been identified as a cause for recurrent morbidity in people with either Type 1 Diabetes (T1D) or Type 2 Diabetes (T2D); however, the understanding of signs and symptoms of Severe Hypoglycemia (SH), as well as when to use glucagon, tend to vary between patients, caregivers, and adult and pediatric endocrinologists (specialists).

Out-of-Hospital Management of Diabetic Emergencies in Germany: Structural and Process Quality

To collect and analyse representative data of structural and process quality in the management of diabetic emergencies in Germany in 2020. A standardised questionnaire comprising detailed items concerning clinically relevant parameters on the structural and process quality of out-of-hospital management of diabetic emergencies was sent nationwide to medical directors of emergency medical service districts (EMSDs). Results were compared with those from a similar study conducted in 2001. The return rate of the questionnaires represented 126 EMSDs, serving a total population of > 40.1 million. Only 4% of ambulances carried glucagon (6% in 2001). In 2020, blood glucose determination increased significantly to 71% of all emergency interventions and to 29% of suspected cardiac emergencies (24% and 15%, respectively, in 2001). In 100% of EMSDs severe hypoglycaemia (SH) was treated by paramedics by administering intravenous dextrose before the arrival of a doctor compared to 63% in 2001. The potential value of nasal glucagon was acknowledged by 43% of responders. In selected patients, treatment of SH was conducted without hospital admission in 78% of EMDs (60% in 2001). Fifty-three percent of medical directors acknowledged the need for further training in diabetic emergencies (47% in 2001). Cooperation for medical education between emergency teams and a diabetes centre was reported by 14% (41% in 2001). Structural and process quality of the management of diabetic emergencies in Germany has improved considerably since 2001. Persisting deficiencies could be improved by providing better medical equipment in ambulances and ongoing education to the entire emergency teams.

51-LB: Emotional Impact of Hypoglycemia and Use of Glucagon: Perspectives of People with T1D

Introduction: Severe hypoglycemia is an ongoing barrier to achieving glycemic targets. Glucagon is an effective, yet underutilized treatment for severe hypoglycemia. This study characterized the emotional impact of severe hypoglycemia, glucagon perceptions, and barriers to glucagon use for people with T1D. Methods: Participants included individuals recruited from the T1D Exchange online community. The current study conducted 7 focus groups consisting of adults with T1D (n = 38, average age 49.4, SD = 16.11 years). Average duration of diabetes was 34.4 years (SD = 17.3) and average self-reported A1c was 6.8% (SD = 0.7). Focus groups were recorded, transcribed, and thematically analyzed. Results: A range of emotions was expressed about severe hypoglycemia including fear, anxiety, stress, frustration, shame, and embarrassment. Due to hypoglycemia unawareness, participants discussed relying on CGM to make hypoglycemia treatment decisions. Multiple participants self-administered glucagon to prevent or treat a severe hypoglycemic event. Although overnight hypoglycemia and CGM alarms were described as important, some participants also viewed them as sleep disruptors for themselves and their partners. Participants frequently identified prescription cost and insurance deductibles as barriers to glucagon use. Participants were also concerned about ease of administration—how difficult it is to prepare the glucagon in an emergency situation. Many participants expressed a preference for auto-injectables over nasal administration. Timing of glucagon action and time to recovery were high priorities. Some participants, while they had not self-administered glucagon, were interested in a mini-dose glucagon they could self-administer. Conclusions: These results provide insight into the real-world impact of diabetes management in persons with T1D and highlight the attitudes about severe hypoglycemia and emergency glucagon treatment. Disclosure A. Hughes: None. K. S. M. Chapman: None. J. Bispham: None. N. M. Heydarian: None. J. Dimsits: Employee; Self; Zealand Pharma A/S. S. A. Weinzimer: Advisory Panel; Self; Dompe, Zealand Pharma A/S, Speaker’s Bureau; Self; Medtronic. W. Wolf: None.

772-P: Portability of Nasal Glucagon for the Rescue of Severe Hypoglycemia: Stability and Performance Evaluation across a Broad Range of Temperatures

Background and Aims: Nasal glucagon is a ready-to-use, drug-device combination therapy for the treatment of severe hypoglycemia. Portability is key, as nasal glucagon should be carried by persons with diabetes at all times. In designing for portability, the medication must allow for exposure to a broad range of temperatures without significant adverse effect on product quality/performance. In this study, we evaluated the stability and performance of nasal glucagon at temperatures ranging from -20 to +30 °C (-4 to +86 °F) in order to mimic real world situations. Methods: Testing focused on characterization of drug product (glucagon amount) and combination product performance (consistent delivery to nasal cavity). Critical quality elements, including chemical purity and content, particle size, actuation force, delivered dose, shot weight, spray pattern and plume geometry, were evaluated after being exposed to temperatures from -20 and +30 °C, a range broader than a typically controlled room temperature product [i.e., Store at Controlled Room Temperature, 20° to 25°C (68° to 77°F); excursions permitted between 15° and 30°C (59° and 86°F)], such as glucagon for injection. Results: All testing demonstrated that 100% of critical quality elements were satisfied. Nasal glucagon could be exposed to frozen (-20 °C), refrigerated (2 to 8°C), and up to 30 °C conditions for the 2-year shelf life. The degradation of glucagon followed Arrhenius kinetics (i.e., slower degradation rates at lower temperatures). Temperature cycling studies showed no significant changes in the chemical/product performance attributes. Conclusions: These analyses indicate no adverse impact to nasal glucagon from the chemical and physical perspective when exposed to frozen, refrigerated, and up to 30 °C conditions. The stability across a broad range of temperatures facilitates the portability of nasal glucagon as a rescue medication for severe hypoglycemia. Disclosure B. W. Pack: Employee; Self; Eli Lilly and Company, Stock/Shareholder; Self; Eli Lilly and Company. J. Melnick: Employee; Self; Eli Lilly and Company, Employee; Spouse/Partner; Eli Lilly and Company. C. Breen: Employee; Self; Eli Lilly and Company. R. Allen: Employee; Self; Eli Lilly and Company. Funding Eli Lilly and Company

344-P: Integrated Safety Analysis of Dasiglucagon for Treatment of Severe Hypoglycemia

Dasiglucagon was developed to provide a fast and effective treatment for severe hypoglycemia (SH) in people with diabetes. An integrated cross-program analysis was performed to assess the safety of dasiglucagon in a representative population of T1DM. Three randomized, placebo-controlled phase 3 trials (2 in adults and 1 in pediatric subjects) were included in the analysis (212 adults and 41 children/adolescents with T1DM). No severe or adverse events (AEs) leading to withdrawal were reported. Most AEs were mild or moderate in severity. Nausea and vomiting were the most-frequent AEs reported with active treatment both in adults and children. No differences in the frequency of nausea and vomiting were observed between adults receiving dasiglucagon versus glucagon. A higher percentage of adolescents experienced these events with dasiglucagon than with glucagon, while no treatment-related imbalance was observed in the 6- to 11-year-old age group. In the pediatric trial, no relationship between exposure (AUC0-5 hr or Cmax) to dasiglucagon, and nausea and vomiting was found. The majority of nausea and vomiting occurred within 1-3 hr and 2-3 hr of dosing, respectively. In conclusion, dasiglucagon 0.6 mg for treatment of SH was found to be generally safe, and the safety profile of dasiglucagon was consistent with that observed across the class of glucagon products. Disclosure S. R. Heller: Advisory Panel; Self; Eli Lilly and Company, Novo Nordisk, Zealand Pharma A/S, Consultant; Self; Zealand Pharma A/S, Other Relationship; Self; Dexcom, Inc., Eli Lilly and Company, MannKind Corporation, Novo Nordisk, Speaker’s Bureau; Self; AstraZeneca, Novo Nordisk. R. Aronson: None. L. Dimeglio: Advisory Panel; Self; MannKind Corporation. T. Danne: Research Support; Self; Abbott Diabetes, Dexcom, Inc., Eli Lilly and Company, Medtronic, Novo Nordisk, Sanofi, Tandem Diabetes Care, Zealand Pharma A/S, Stock/Shareholder; Self; DreaMed Diabetes, Ltd. T. Battelino: Advisory Panel; Self; Eli Lilly and Company, Medtronic, Sanofi, Research Support; Self; European Union, National Institute of Diabetes and Digestive and Kidney Diseases, Novartis Pharmaceuticals Corporation, Novo Nordisk, Sanofi, Slovenian Research Agency, Zealand Pharma A/S, Speaker’s Bureau; Self; Abbott Diabetes, AstraZeneca, Dexcom, Inc., Eli Lilly and Company, Medtronic, Novo Nordisk, Pfizer Inc., Roche Diabetes Care, Sanofi, Stock/Shareholder; Self; DreaMed Diabetes, Ltd. T. S. Bailey: Consultant; Self; Abbott Diabetes, LifeScan, Novo Nordisk, Sanofi, Research Support; Self; Abbott, Abbott Diabetes, Biolinq, Capillary Biomedical, Inc., Dexcom, Inc., Eli Lilly and Company, Kowa Research Institute, Inc., Lexicon Pharmaceuticals, Inc., Livongo, Medtronic, Medtrum Technologies, Novo Nordisk, REMD Biotherapeutics, Sanofi, Sanvita, Viacyte, Inc., vTv Therapeutics, Zealand Pharma A/S, Speaker’s Bureau; Self; BD, Medtronic, Sanofi. R. Tehranchi: Employee; Self; Zealand Pharma A/S. L. J. Klaff: Research Support; Self; Abbott Diabetes, Dong-A ST Co. Ltd., Gan & Lee Pharmaceuticals, Lexicon Pharmaceuticals, Inc., Lilly Diabetes, Medtronic, Novo Nordisk, Oramed Pharmaceuticals, Inc., Pfizer Inc., REMD Biotherapeutics. T. Pieber: Advisory Panel; Self; ADOCIA, Arecor, AstraZeneca, Eli Lilly and Company, Novo Nordisk A/S, Sanofi, Research Support; Self; AstraZeneca, Novo Nordisk A/S. U. Hovelmann: None. L. Plum-moerschel: None. A. E. Melgaard: Employee; Self; Zealand Pharma A/S.

Dasiglucagon, a Ready-To-Use Glucagon Analog, For Rapid And Effective Treatment of Severe Hypoglycemia: a Phase 3, Randomized Controlled Trial in Children With Type 1 Diabetes

Background Dasiglucagon, a novel glucagon analog, is in development for the treatment of hypoglycemia. Objective: To assess the safety and efficacy of dasiglucagon via HypoPal® auto-injector as a rapid and dependable treatment for hypoglycemia in children with T1DM. Methods NCT03667053, a Phase 3, double-blind trial (N=42), randomized children (6-11 years: n=16; 12-17 years: n=26), 2:1:1 to a single subcutaneous injection of dasiglucagon (0.6 mg), placebo, or glucagon (GlucaGen®) following induced hypoglycemia. The primary endpoint was time to plasma glucose (PG) recovery (first PG increase ≥ 20 mg/dL after treatment initiation). Results Median time (95% CI) to PG recovery was 10 min (8, 12) for dasiglucagon vs 30 min (20, –) for placebo (primary comparison, P < 0.001); and 10 min (8, 12) for GlucaGen®. Using linear interpolation, the median estimated true time to recovery was 8.7 min (6.9, 10.6) for dasiglucagon, 29.3 min (18.5, –) for placebo and 9.8 min (7.4, 10.6) for GlucaGen®. No safety concerns noted. Nausea and vomiting, known glucagon side effects, were reported for dasiglucagon (6-11 years: nausea [25%], vomiting [25%]; 12 17 years: nausea [92%], vomiting [67%]) and GlucaGen® (6-11 years: nausea [50%], vomiting [25%]; 12-17 years: nausea [17%], vomiting [0%]). No relationship was found between dasiglucagon exposure (AUC0 5h or Cmax) and nausea or vomiting. Conclusions In children with T1DM, dasiglucagon results in rapid and reliable correction of PG levels following induced hypoglycemia. The overall safety profile of dasiglucagon is similar to that of lyophilized glucagon, offering a convenient, rapid, and ready-to-use treatment for severe hypoglycemia.

Ready-to-use Dasiglucagon Injection as a Rapid and Effective Treatment for Severe Hypoglycemia

Background: Severe hypoglycemia (SH) is an all too common and feared complication of insulin therapy and necessitates urgent medical intervention. Dasiglucagon, a novel peptide analog of human glucagon, is uniquely stable in aqueous solutions and is currently in development for treatment of SH via a ready-to-use auto-injector. Objective: To assess the efficacy and safety of dasiglucagon injection as a rapid and dependable treatment for SH. Methods: In the pivotal Phase 3 trial, NCT03378635, dasiglucagon (0.6 mg) was compared to placebo, and GlucaGen®, in adults with type 1 diabetes mellitus (N=168), randomized (2:1:1) after insulin-induced hypoglycemia. The primary endpoint was time to plasma glucose (PG) recovery, defined as first PG increase of 20 mg/dL after treatment initiation. Results: The median time to recovery was 10 min for dasiglucagon vs 12 and 40 min for GlucaGen® and placebo, respectively. In the dasiglucagon arm, 65% of patients recovered within 10 min vs 49% receiving GlucaGen®. After 15 min, 99% of dasiglucagon-treated patients recovered vs 95% treated with GlucaGen®. Dasiglucagon was generally well tolerated. Similar frequencies of nausea (55% and 53%), and vomiting (23% and 19%), were reported with dasiglucagon and GlucaGen®, respectively. Injection-site reactions 30 minutes post- dose were reported in 2%, 7%, and 5% of patients in the dasiglucagon, GlucaGen®, and placebo groups, respectively. Conclusions: Dasiglucagon 0.6 mg demonstrated rapid and efficacious treatment for SH. The stability of dasiglucagon in aqueous formulation supports its further development as a unique treatment option for the management of the entire spectrum of mild, moderate, and SH.

Pharmacology Update: Emergency Medications for Hypoglycemia in Diabetes.

Children and adults with Type 1 and Type 2 diabetes are at risk for severe hypoglycemia, an unpredictable and potentially life-threatening situation. Severe hypoglycemia creates low blood glucose levels in which a person has an altered mental status or physical symptoms that require assistance from another individual to treat the hypoglycemia. Treatment of severe hypoglycemia is a medical emergency and prompt treatment is important for the well-being of students with diabetes. If left untreated, severe hypoglycemia can lead to death. Glucagon is a medication used to treat severe hypoglycemia outside of a healthcare facility. Recently, more stable and easier to use formulations of glucagon have become available. The purpose of this pharmacology update is to describe two new formulations of ready to use glucagon: an intranasal and subcutaneous, autoinjector formulation.

129-LB: Evaluation of Attitudes towards Two Glucagon Delivery Devices for Rescue Treatment of Severe Hypoglycemia

Objective: This study assessed preference, hesitation using, perceived ease of use, and feeling prepared and protected for nasal glucagon (NG) vs. autoinjector glucagon (AI) for rescue treatment of severe hypoglycemia (SH) among people with diabetes (PWDs), caregivers (CGs) and acquaintances (AQs). Methods: US PWDs (type 1 or 2, on insulin; n=405), CGs (n=313) and AQs (n=305) completed an online survey, after viewing a description of SH and graphics and descriptions of NG and AI (based on publicly available information at the time of study; prior to access to the final commercial device or their instructions for use). Respondents rated strength of preference for NG vs. AI on 16 attributes using direct elicitation (7-point scale; 1 = ‘very strongly prefer AI‘ and 7 = ‘very strongly prefer NG’, 4 = neutral); 4 items focused on overall preference, being less likely to hesitate using, perceived ease of use, and feeling prepared and protected, and 12 items were averaged to create a preference scale (e.g., size of device, less complicated). This measure was developed using established guidelines for instrument development, including qualitative research and assessment of the measure’s psychometric properties. One sample t-tests evaluated whether mean preference ratings differed from a neutral score. Results: Across PWDs, CGs, and AQs, NG was preferred over AI (all P&amp;lt;0.001 compared to neutral) on overall preference (4.5, 4.9, and 5.4, respectively), being less likely to hesitate using (4.8, 5.1, and 5.4, respectively), perceived ease of use (4.8, 5.1, and 5.4, respectively) and the preference scale (4.7, 5.0, and 5.3, respectively). CGs and AQs preferred NG vs. AI on feeling prepared and protected (4.6 and 4.8, respectively; both P&amp;lt;0.001 compared to neutral); PWDs were neutral (4.1, P=0.376). Conclusions: This study provides insights on PWDs’, CGs’ and AQs’ attitudes towards new glucagon devices, which may be considered when making product choices among the glucagon delivery systems. Disclosure S.K. Bajpai: Employee; Self; Eli Lilly and Company. J. Cambron-Mellott: Other Relationship; Self; Eli Lilly and Company. N.K. Raibulet: Employee; Self; Eli Lilly and Company. E.Y. Peck: None. J. Poon: Employee; Self; Eli Lilly and Company. Q. Wang: Employee; Self; Eli Lilly and Company. B. Mitchell: Employee; Self; Eli Lilly and Company. Stock/Shareholder; Self; Eli Lilly and Company. O. Will: Other Relationship; Self; Eli Lilly and Company. J. Babrowicz: Other Relationship; Self; Eli Lilly and Company. C.J. Child: Employee; Self; Eli Lilly and Company. Stock/Shareholder; Self; Eli Lilly and Company. K. Beusterien: Other Relationship; Self; Eli Lilly and Company.

1053-P: Dasiglucagon Hypopal Autoinjector as a Fast and Effective Treatment for Severe Hypoglycemia: Results of a Phase 3 Trial

Severe hypoglycemia is a major concern for patients with diabetes on insulin therapy. Rescue requires caregivers to provide effective treatment, including glucagon injections. Dasiglucagon is a stable glucagon analog in development to be administered with the HypoPal® auto-injector for treatment of severe hypoglycemia. This phase 3 trial, ZP4207-17145, assessed the clinical efficacy and safety of 0.6 mg dasiglucagon subcutaneous (SC) administered via the HypoPal® auto-injector compared with placebo. In total, 45 eligible patients with T1D were randomized (3:1) to dasiglucagon or placebo and dosed following induced hypoglycemia. The primary endpoint was time to plasma glucose (PG) recovery, defined as first PG increase ≥20 mg/dL after treatment initiation without rescue glucose. Dasiglucagon injection provided a fast and effective increase in PG. The median time (95% CI) to recovery based on sampling time was 10 (8.0, 12.0) min for dasiglucagon and 35 (20.0, -) min for placebo (p&amp;lt;0.0001). The median (95% CI) estimated true time to recovery (interpolated between sampling times) was 9.3 (7.8, 10.3) min for dasiglucagon and 25.8 (19.2, 34.8) min for placebo. Nausea and vomiting are well-known side effects of glucagon and were reported in 61.8% and 29.8% of patients receiving dasiglucagon, respectively. Nausea was reported in 10% of patients receiving placebo. No safety concerns were raised for dasiglucagon. In conclusion, dasiglucagon 0.6mg SC administered via the HypoPal® auto-injector provided fast and effective recovery from hypoglycemia. The results are consistent with previously reported results from a pivotal phase 3 trial testing dasiglucagon administered via a pre-filled syringe, NCT03378635, where a median time to recovery of 10 min was also observed. Disclosure T.S. Bailey: Consultant; Self; Abbott, LifeScan, Inc., Novo Nordisk A/S, Sanofi US. Research Support; Self; Abbott, Ascensia Diabetes Care, Capillary Biomedical, Inc., Dance Biopharm Holdings, Inc., Dexcom, Inc., Diasome Pharmaceuticals, Inc., Eli Lilly and Company, Kowa Pharmaceuticals America, Inc., Lexicon Pharmaceuticals, Inc., Medtronic, Medtrum, Novo Nordisk A/S, REMD Biotherapeutics, Sanofi-Aventis, Senseonics, Viacyte, Inc., vTv Therapeutics, Zealand Pharma A/S. Speaker’s Bureau; Self; Medtronic, Sanofi US. J. Willard: None. L.J. Klaff: Research Support; Self; Abbott, Ascensia Diabetes Care, Dexcom, Inc., Lilly Diabetes, Medtronic, Novo Nordisk A/S, REMD Biotherapeutics, Roche Diabetes Care, Sanofi-Aventis, Xeris Pharmaceuticals, Inc., Zealand Pharma A/S. L.S. List: Employee; Spouse/Partner; Novo Nordisk A/S. Employee; Self; Zealand Pharma A/S. Stock/Shareholder; Spouse/Partner; Novo Nordisk A/S. Stock/Shareholder; Self; Novo Nordisk A/S, Zealand Pharma A/S. A.E. Melgaard: Employee; Self; Zealand Pharma A/S. R. Tehranchi: Employee; Self; Zealand Pharma A/S.

180-OR: Dasiglucagon as a Fast and Effective Treatment for Severe Hypoglycemia in Children with Diabetes

Dasiglucagon is a stable glucagon analog being developed in the HypoPal® auto-injector to address the need for easy-to-use, fast and effective treatment of severe hypoglycemia in individuals with diabetes. In this pediatric Phase 3 trial, ZP4207-17086, the clinical efficacy and safety of 0.6 mg dasiglucagon administered subcutaneously (SC) (same dose as adults) was compared to placebo and with reference to GlucaGen®. In total, 42 eligible children with T1D between 6 and 17 years (6-11 years: 16 children and 12-17 years: 25 children) were randomized (2:1:1) to dasiglucagon, placebo or GlucaGen® and dosed following induced hypoglycemia. The primary endpoint was time to plasma glucose (PG) recovery, defined as first PG increase ≥20 mg/dL after treatment initiation without rescue glucose. The results showed that dasiglucagon 0.6 mg SC induced a fast and effective PG increase. The median time (95% CI) to recovery based on sampling time was 10 (8, 12) min for dasiglucagon vs. 30 (20, -) min for placebo (p&amp;lt;0.001); and 10 (8, 12) min for GlucaGen®. The estimated true time to recovery (interpolated between sampling times) showed that the median (95% CI) time was 8.7 (6.9, 10.6) min for dasiglucagon, 29.3 (18.5, -) min for placebo and 9.8 (7.4, 10.6) min for GlucaGen®. Nausea and vomiting are known side effects following administration of glucagon products and were reported for active treatments only: with dasiglucagon (6-11 years; nausea: 25% and vomiting: 25%; 12-17 years; nausea: 92% and vomiting: 67%) and with GlucaGen® (6-11 years; nausea: 50% and vomiting: 25%; 12-17 years; nausea: 17% and vomiting: 0%). No relationship between exposure (AUC0-5 hr or Cmax) to dasiglucagon and nausea and vomiting was found. No safety concerns were raised for dasiglucagon within the trial. In conclusion, consistent with adult phase 3 trials this study demonstrated a fast, effective treatment response with a median time to recovery of 10 min in children ≥ 6 years, and an overall safety profile similar to glucagon. Disclosure T. Battelino: Advisory Panel; Self; Medtronic, Sanofi. Consultant; Self; Indigo Diabetes. Research Support; Self; Medtronic, Novo Nordisk A/S, Zealand Pharma A/S. Speaker’s Bureau; Self; Abbott, AstraZeneca, Dexcom, Inc., Lilly Diabetes, Medtronic. Stock/Shareholder; Self; DreaMed Diabetes. R. Tehranchi: Employee; Self; Zealand Pharma A/S. A.E. Melgaard: Employee; Self; Zealand Pharma A/S. D. Skydsgaard: Employee; Self; Zealand Pharma A/S. Stock/Shareholder; Self; Novo Nordisk A/S. Stock/Shareholder; Spouse/Partner; Novo Nordisk A/S, Roche Diabetes Care. T.S. Bailey: Consultant; Self; Abbott, LifeScan, Inc., Novo Nordisk A/S, Sanofi US. Research Support; Self; Abbott, Ascensia Diabetes Care, Capillary Biomedical, Inc., Dance Biopharm Holdings, Inc., Dexcom, Inc., Diasome Pharmaceuticals, Inc., Eli Lilly and Company, Kowa Pharmaceuticals America, Inc., Lexicon Pharmaceuticals, Inc., Medtronic, Medtrum, Novo Nordisk A/S, REMD Biotherapeutics, Sanofi-Aventis, Senseonics, Viacyte, Inc., vTv Therapeutics, Zealand Pharma A/S. Speaker’s Bureau; Self; Medtronic, Sanofi US. L. DiMeglio: None. T. Danne: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Medtronic, Novo Nordisk A/S, Sanofi.

1074-P: Nasal Glucagon Reversed Insulin-Induced Hypoglycemia in Adults with Diabetes: A Pooled Analysis

Background: Nasal glucagon (NG), a ready-to-use drug-device combination for treatment of severe hypoglycemia, contains 3 mg glucagon dry powder that is absorbed passively through nasal mucosa. We examined the efficacy and safety of NG compared to 1 mg injectable glucagon (IG) in reversing insulin-induced hypoglycemia in a global population of adults with T1D or T2D. Notably, this is the first analysis including pooled T2D data. Methods: Post-hoc analyses used data from 3 randomized, cross-over studies. Treatment success was defined as an increase in BG to ≥70 mg/dL or an increase of ≥20 mg/dL from nadir BG within 30 min of receiving glucagon. Tolerability was assessed using treatment-emergent adverse events and a symptom questionnaire. Results: In the T1D+T2D pooled analysis, 99.5% (213/214) of NG and 100% (214/214) of IG patients achieved treatment success in a mean time (preparation time excluded) of 13 and 11 min, respectively. All NG T2D patients (N=41) achieved treatment success. NG and IG induced similar BG changes (Figure). NG and IG had similar incidences of nausea and vomiting, with NG having a higher rate of side effects related to nasal administration [headache (13% NG, 7% IG), nasal discomfort (4% NG, 1% IG), etc.]. Separate T1D and T2D analyses showed similar results as T1D+T2D. Conclusion: NG was efficacious and well-tolerated in reversing insulin-induced hypoglycemia in adults with T1D or T2D. Disclosure E.R. Seaquist: Advisory Panel; Self; MannKind Corporation, Zucara Therapeutics Inc. Other Relationship; Self; American Board of Internal Medicine, Endocrine Society, International Hypoglycemia Study Group. K. Khunti: Advisory Panel; Self; Amgen, AstraZeneca, Bayer AG, Berlin-Chemie AG, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Menarini Group, Merck Sharp &amp; Dohme Corp., Napp Pharmaceuticals, Novartis AG, Novo Nordisk A/S, Roche Pharma, Sanofi-Aventis, Servier. Board Member; Self; AstraZeneca, Eli Lilly and Company, Merck Sharp &amp; Dohme Corp., Novo Nordisk A/S, Sanofi-Aventis. Consultant; Self; Amgen, AstraZeneca, Bayer AG, Berlin-Chemie AG, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Menarini Group, Merck Sharp &amp; Dohme Corp., Napp Pharmaceuticals, Novartis AG, Novo Nordisk A/S, Roche Pharma, Sanofi-Aventis, Servier. Research Support; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Merck Sharp &amp; Dohme Corp., Novartis AG, Novo Nordisk A/S, Pfizer Inc., Sanofi-Aventis, Servier. Speaker’s Bureau; Self; Amgen, AstraZeneca, Bayer AG, Berlin-Chemie AG, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Menarini Group, Merck Sharp &amp; Dohme Corp., Napp Pharmaceuticals, Novartis AG, Novo Nordisk A/S, Roche Pharma, Sanofi-Aventis, Servier. M.X. Zhang: Employee; Self; Eli Lilly and Company. Stock/Shareholder; Self; Eli Lilly and Company. Q. Wang: Employee; Self; Eli Lilly and Company. Y. Takita: Employee; Self; Eli Lilly Japan K.K. C.J. Child: Employee; Self; Eli Lilly and Company. Stock/Shareholder; Self; Eli Lilly and Company. Y. Nagai: Employee; Self; Eli Lilly Japan K.K. Stock/Shareholder; Self; Eli Lilly and Company. Y. Yan: Employee; Self; Eli Lilly and Company. M. Matsuhisa: Research Support; Self; Daiichi Sankyo, Mitsubishi Tanabe Pharma Corporation, Novartis Pharma K.K., Novo Nordisk Inc., Sanofi, Sysmex Corporation. Speaker’s Bureau; Self; Astellas Pharma Inc., Eli Lilly Japan K.K., Merck Sharp &amp; Dohme Corp., Mitsubishi Tanabe Pharma Corporation, Novo Nordisk Inc., Sanofi K.K., Takeda Pharmaceutical Company Limited. Funding Eli Lilly and Company

1085-P: Nasal Glucagon Was Efficacious in Reversing Insulin-Induced Hypoglycemia without Increasing Risk of Secondary Hyperglycemia

Background: Nasal glucagon (NG), a ready-to-use therapy for treatment of severe hypoglycemia, contains 3 mg glucagon dry powder absorbed passively through nasal mucosa. We evaluated efficacy, pharmacodynamics (PD), and safety of NG compared to injectable glucagon (IG) in reversing insulin-induced hypoglycemia in Caucasian and Japanese adults with T1D or T2D. Methods: Post-hoc analyses used data from 2 randomized, cross-over studies. Treatment success was defined as an increase in BG to ≥70 mg/dL or an increase of ≥20 mg/dL from nadir BG within 15 min of receiving glucagon. PD data, including area under the curve above 140 mg/dl [∆140 AUC (1-4 hr)], were used to evaluate the risk of secondary hyperglycemia. Tolerability was assessed with treatment-emergent adverse events and a symptom questionnaire. Results: A similar proportion of NG [97.8% (131/134)] and IG patients [97.0% (130/134)] achieved treatment success. Geometric least square mean BGmax for NG and IG were 194 and 205 mg/dL (p&amp;lt;0.001), respectively. NG had significantly lower ∆140 AUC (1-4 hr) (p&amp;lt;0.001). NG had similar rates of nausea and vomiting versus IG, with higher rates of side effects related to nasal administration. Conclusions: NG was efficacious and well-tolerated in reversing insulin-induced hypoglycemia in adults with T1D or T2D and did not increase the risk of secondary hyperglycemia compared to IG. Disclosure Y. Yan: Employee; Self; Eli Lilly and Company. Q. Wang: Employee; Self; Eli Lilly and Company. C.J. Child: Employee; Self; Eli Lilly and Company. Stock/Shareholder; Self; Eli Lilly and Company. M.X. Zhang: Employee; Self; Eli Lilly and Company. Stock/Shareholder; Self; Eli Lilly and Company. Funding Eli Lilly and Company

8-LB: Emotional Impact of Hypoglycemia and Use of Glucagon: Perspectives of People with T1D and Caregivers of Minors with T1D

Severe hypoglycemia is a complication of insulin therapy and a continuing barrier to achieving glycemic targets at every age. Glucagon, a drug that has been on the market for several decades, is an effective treatment for severe hypoglycemia, but is underutilized. The emotional impact of severe hypoglycemia and the emergency use of glucagon is not clear. This study aimed to understand current perceptions of glucagon from both the perspective of people with T1D and people likely to aid in an emergency situation. All participants were recruited from T1D Exchange Glu (www.myglu.org), an online community for individuals living with T1D. The current study conducted interviews with people with T1D (n=9, average age 44.7 years) and caregivers (n=8, average age 37.8 years) of minors with T1D. Interviews were recorded, transcribed, and thematically analyzed. Participants described experiences and emotions surrounding severe hypoglycemia, importance of specific glucagon characteristics, and priorities during severe hypoglycemia. Participants expressed on a 1-10 scale the importance of glucagon’s time to recovery (average: 8.56), mode of administration (average: 8.56), cost (average: 5.67), and not requiring refrigeration (average: 9.56). Themes among participants with T1D included feelings of distress, fear, and helplessness; common caregiver themes included feeling intimidated by the administration of glucagon. People with T1D discussed how they make decisions during a hypoglycemic emergency and rely on others for decision-making. Participants described their ideal glucagon and emphasized how fast glucagon needs to be, the desire for minimal side effects, and different administration types. These results provide insight into the real-world impact of diabetes on both persons with T1D and their caregivers and highlight the attitudes about severe hypoglycemia and emergency treatment with glucagon. Disclosure A. Hughes: None. J. Bispham: None. L. Fuller: None. W. Wolf: None. S.A. Fitch: Employee; Self; Zealand Pharma A/S. S.A. Weinzimer: Consultant; Spouse/Partner; Tandem Diabetes Care. Consultant; Self; Zealand Pharma A/S. Speaker’s Bureau; Self; Insulet Corporation.