ADA 81st Symposium: The Effect of Nasal Glucagon in Insulin-Induced Hypoglycemia 

The preparation of nasal glucagon is immediate and intended for use in emergency hypoglycemia events, but how well can it reverse these events? 

Patients with diabetes always risk facing a hypoglycemic event, especially those patients with type 1 diabetes. One option to combat severe hypoglycemic events is injectable glucagon, but another option is to administer glucagon through the nose. While both forms effectively treat patients who experience hypoglycemic episodes, the question becomes, how do they handle the varying levels of these episodes? This question is what this study is trying to answer and is the purpose of this study.  

This study is a post-hoc analysis that gathered its data from 3 randomized crossover studies. In those studies, hypoglycemic events in patients with type 1 or type 2 diabetes were due to intravenous regular insulin infusions. The infusions continued until the patients’ blood glucose level was less than 60 mg/ dL. Then, after a roughly five-minute waiting period, the patients received one of the intervention groups, 3 mg nasal glucagon (n= 214) or 1 mg injectable glucagon (n= 214). The mean of the lowest blood glucose was 48.1 ±7.93 mg/ dL for nasal glucagon and 50.2 ±7.84 mg/ dL for injectable glucagon. There were four subgroups for blood glucose, ≥60 mg/ dL, ≥50 and <60 mg/ dL, ≥40 and <50 mg/ dL, and <40 mg/ dL. The evaluated parameters were blood glucose response, treatment success, and treatment-emergent adverse events (TEAEs) during this study. This study’s definition of treatment success was reaching a blood glucose level of ≥70 mg/ dL or increasing ≥20 mg/ dL from the lowest point in blood glucose within 30 minutes of receiving glucagon.  

The data has shown that within 30 minutes, the increase in blood glucose levels was similar among all subgroups, respective to their lowest blood glucose, with the administration of nasal glucagon. Of note, every subgroup for nasal glucagon managed to reach a mean of 100 mg/ dL. However, as for injectable glucagon, the difference in the increase in blood glucose levels was apparent between the two subgroups <50 mg/ dL from the two subgroups ≥50 mg/ dL. The <40 mg/ dL subgroup did not reach a mean of 100 mg/ dL, while the other three subgroups for the injectable glucagon intervention did. 

Mean Time to Blood Glucose Increase of ≥20 mg/ dL 

• Nasal Glucagon (Blood Glucose Range: Minutes) 
  • <40: 14.2 
  • ≥40 and <50: 14.4 
  • ≥50 and <60: 13.2 
  • ≥60: 12.3 

• Injectable Glucagon 
  • <40: 13.4 
  • ≥40 and <50: 12.6 
  • ≥50 and <60: 11.3 
  • ≥60: 10.6 

 The scatter plot of max blood glucose increase versus nadir blood glucose value demonstrated a significant association for injectable glucagon (P-Value <0.001) but none for nasal glucagon (P-Value= 0.074). This association suggested that depending on the severity, the increase of blood glucose could be lower in the more severe hypoglycemia ranges than those of lesser severity. The mean max blood glucose for nasal glucagon was 176.2 mg/ dL, while injectable glucagon was 191.3 mg/ dL throughout the study.  

For time to treatment success based on the subgroup, there was an association for injectable glucagon (P-Value <0.001) but none for nasal glucagon (P-Value= 0.566). In other words, for nasal glucagon, the time to treatment success was the same regardless of the severity of the hypoglycemia. In contrast, in injectable glucagon, the severity played a role in the glucose level to reach success. However, regardless of the time to treatment outcomes for nasal and injectable glucagon, the success was 99.5% and 100%, respectively. Furthermore, the results from TEAE showed that neither nasal nor injectable glucagon had a significant association with nausea, vomiting, and headaches based on the subgroup ranges.   

To sum up the data, nasal glucagon was effective and safe in treating insulin-induced hypoglycemia regardless of the severity. As mentioned previously, both treatment options provide a highly successful reversal of hypoglycemia. However, injectable glucagon was associated with the severity of hypoglycemia and both time to treatment success and maximum blood glucose increase within 30 minutes.  

Practice Pearls 

• Nasal glucagon proved effective and safe in patients who experienced insulin-induced hypoglycemia across differing severities of low blood glucose.  
• Both options have incredibly high success rates for treating insulin-induced hypoglycemia. 
• The extent to which blood glucose increased was dependent on the nadir blood glucose for injectable glucagon. 

YALE, JEAN-FRANÇOIS, et al. “348-P: Nasal Glucagon Was Efficacious in Reversing Insulin-Induced Hypoglycemia across a Range of Nadir Blood Glucose Levels.” American Diabetes Association 81st Scientific Sessions. Diabetes, June 25, 2021 (Requires ADA Symposium login.) 

Alan Martinez, PharmD Candidate, University of South Florida Taneja College of Pharmacy