ADA 2021: Dasiglucagon and the Effects Among Various Demographics

Dasiglucagon is a glucagon analog stable in an aqueous formulation with FDA approval for severe hypoglycemia use. The target population is patients with diabetes who are six years of age and older, but how effective is it among other subgroups? 

Severe hypoglycemia presents a potential risk in patients with diabetes, especially among those with multiple therapies or those who dose an inappropriate amount of insulin. A possible resolution to treat hypoglycemia is glucagon; unfortunately, this route is not taken advantage of as much as it is supposed to be. This problem could stem from the reconstitution process required when preparing injectable glucagon, especially when time is of utmost importance. Unlike those options, dasiglucagon is already ready for immediate use as an aqueous formulation and has effectively treated severe hypoglycemia. However, the effectiveness in various subgroups such as sex, age, ethnicity, region, BMI, duration of diabetes, injection site, and baseline glucose remain unclear. Therefore, the purpose of this study was to assess whether dasiglucagon was effective among these various subgroups. 

This study is an integrated efficacy analysis with data from four trials with similar study conditions that followed patients with type 1 diabetes who had insulin-induced hypoglycemia (n= 220). The baseline characteristics for this study had shown that most patients were non-Hispanic or Latino males with an age range of 18 to 65 years. The primary endpoint of this analysis was the time to glucose recovery, defined as a glucose increase of ≥20 mg/ dL with no addition of intravenous glucose administration.  

 To provide the efficacy of dasiglucagon compared to placebo, one of the trials demonstrated that the time to glucose recovery was a median of 10 minutes [95% Confidence Interval (CI): 10 to 10] compared to the placebo’s 40 minutes (95% CI: 30 to 40). Furthermore, the comparison between dasiglucagon and placebo showed that dasiglucagon dominated with a shorter time to the glucose recovery and proved to be statistically significant (P-Value <0.001).  

The first subgroup from this integrated analysis had compared the sex of the patients. Female (n= 91) and male (n= 129) were equivalent in a median time of 10 minutes. The subgroup for age differed between patients ≥65 (n= 6) and those ≥18 to <65 years of age (n= 214). While the patients between 18 and 65 years had a median time of 10 minutes to glucose recovery, the ≥65 group was 15 minutes. However, the few patients in the ≥65 group hindered a proper comparison between both age groups. The same dilemma had occurred in the ethnicity subgroup, as there were too few Hispanic or Latino patients (n= 7) to non-Hispanic or Latino (n= 196); this caused a wide range of time for the Hispanic or Latino subgroup. Nonetheless, the non-Hispanic or Latino subgroup had a median time of 10 minutes, similar to other results. Next, the region subgroup compared patients from the United States (n= 46) to those who were not (n= 174), and both groups had a median time of 10 minutes.  

The following subgroup dealt with the comparison among different BMIs, <25 (n= 97), ≥25 to <30 (n= 88), ≥30 to <35 (n= 29) and ≥35 (n= 6). Subgroups <25 and ≥25 to <30 both had mean times of 10 minutes while ≥30 to <35 had a slightly higher value and ≥35 had a wide range due to fewer patients. The duration of the diabetes subgroup consisted of <20 years of diabetes or ≥20 years of diabetes, both of which had a median time of 10 minutes. The injection site subgroup consisted of the abdomen (n= 132), buttocks (n= 45), deltoid (n= 16), and thigh (n= 27), all of which shared the same median time of 10 minutes. The final subgroup was baseline glucose, both groups <54 (n= 41) and ≥54 (n= 179) had a median time of 10 minutes.  

To summarize the data, dasiglucagon was adequate across the majority of the subgroups except for groups where patient numbers were too low to conclude. In addition, most subgroups had a mean time to glucose recovery of 10 minutes when using dasiglucagon. However, a limitation of this study was the small sample size; thus, further research with a larger sample size could support the findings of this analysis.  

Practice Pearls: 

• The effectiveness of dasiglucagon was consistent among the various subgroups. 
• When using dasiglucagon, the majority median time to recovery was 10 minutes. 
• Dasiglucagon for severe low blood glucose is a reliable option compared to formulations where reconstitution is required.  

BATTELINO, TADEJ, et al. “345-P: The Next Generation Glucagon Analog Dasiglucagon Consistently Achieves Rapid Recovery from Hypoglycemia across Subgroups.” American Diabetes Association 81st Scientific Sessions. Diabetes, June 25, 2021 

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