Glucagon Analog Stops Hypoglycemia Faster Than Carbs

Mitchel L. Zoler, PhD

June 24, 2022

Dasiglucagon, a glucagon analog approved for treating severe hypoglycemia, also appeared to be effective and highly acceptable for patients with type 1 diabetes with nonsevere hypoglycemia in a controlled, crossover study of 24 patients.

In the head-to-head comparison with the main nonpharmacologic option for treating nonsevere hypoglycemia — ingestion of fast-acting carbohydrates — dasiglucagon (Zegalogue) produced similar times within the target range for blood glucose levels but worked faster, shaving 5 minutes off the median time it took for patients to achieve euglycemia following self-administration of the agent compared with the median lag using orally ingested carbohydrates, Christian Laugesen, MD, said at the American Diabetes Association (ADA) 82nd Scientific Sessions.

The median times to euglycemia were 16 minutes using dasiglucagon and 21 minutes with oral carbohydrates, said Laugesen, an endocrinologist at the Steno Diabetes Center in Copenhagen, Denmark.

"Every Minute Counts"

That time difference may seem modest, but it's clinically meaningful, he said. "When patients experience hypoglycemia symptoms, every minute counts," Laugesen stressed.

Success in resolving hypoglycemia occurred in 144 of 168 episodes (86%) while taking dasiglucagon and in 168 of 216 episodes (78%) using only carbohydrates, a significant difference.

Faster action and a higher rate of resolution may, in part, explain the high level of satisfaction with dasiglucagon by patients in the study. When the researchers asked participants at the end of the open-label study how likely they were to use dasiglucagon as part of their diabetes management, 88% said they would be very likely to continue using the agent, with an additional 8% saying that they would likely use it, Laugesen reported.

"Impressive" Patient Satisfaction

That's "an impressive level of patient satisfaction," commented Sadia Ali, MD, an endocrinologist at UT Southwestern Medical Center in Dallas, who was not involved with the study.

Another apparent advantage of dasiglucagon is that patients self-administer it with an autoinjector or prefilled syringe, giving patients tight control of their dosing. Patients are vulnerable to overdosing when self-administering fast-acting carbohydrates, which can result in weight gain when nonsevere hypoglycemic episodes are frequent, Ali noted.

"Hypoglycemia makes patients nervous, and that often makes patients overdo their carbohydrates," Ali said in an interview.

In the study, the only delivery mechanism patients could use was an autoinjector pen, which generally delivered an 80-µg subcutaneous dose. However, 24% of study participants self-administered more than one dose of dasiglucagon, and 25% supplemented their dasiglucagon treatment with carbohydrate ingestion, neither of which were protocol violations. The study design also allowed participants to use the two interventions to not only self-treat an incident episode of hypoglycemia, but also for prophylaxis to head-off anticipated episodes resulting from impending exercise.

The single-center study enrolled adults who were diagnosed with type 1 diabetes for at least 2 years, used both an insulin pump and continuous glucose monitoring, and maintained an A1c of no more than 8.5%. Participants also had to exercise at least twice a week and their glucose monitoring had to show at least four times during the 2 weeks prior to enrollment when their blood glucose fell below 3.9 mmol/L. The study excluded people who were taking any antidiabetes medication other than insulin, as well as those without awareness of their hypoglycemic episodes.

The 24 enrolled patients were an average age of 44 years, their average duration of type 1 diabetes was 23 years, most (58%) were women, average A1c was 7.3%, and average body mass index was 27.8 kg/m2.

A Nonsignificant Difference in the Primary Outcome

The study's primary outcome was time participants stayed in the target blood glucose range of 3.9-10.0 mmol/L during their 2 weeks on each of the two study regimens: either carbohydrate ingestion exclusively or dasiglucagon self-injections plus carbohydrate ingestion at the discretion of each participant. Following random assignment to either of the two groups, participants underwent a 3- to 7-day washout, followed by 2 weeks on the alternate regimen.

Time within the target blood glucose range occurred during 63.9% of the 2 weeks on dasiglucagon, and during 61.5% of the 2 weeks on carbohydrates only, a difference that was not significant. Time spent with a hypoglycemic episode with blood glucose below 3.9 mmol/L was 2.6% of the 2 weeks in the dasiglucagon group and 3.1% of the 2 weeks in the carbohydrates only group, also a nonsignificant difference.  

Total carbohydrate intake fell by 11% during the dasiglucagon-treatment period compared with the control period. Some adverse events were more common during dasiglucagon use. Nausea was reported by 33% of people during the dasiglucagon phase and 17% during the control phase. Headache was reported by 42% during the dasiglucagon phase and 33% during the control period. "Palpitations" affected 13% while taking dasiglucagon and 4% during the control phase.

Dasiglucagon was approved by the US Food and Drug Administration in 2021 for the treatment of severe hypoglycemia in people with diabetes age 6 years and older. The approval was based on results from three randomized, double-blind, placebo-controlled phase 3 studies of dasiglucagon in children age 6-17 years and adults with type 1 diabetes.

The study received funding and study drug from Zealand Pharma, the company that markets dasiglucagon (Zegalogue). Laugesen and Ali have reported no relevant financial relationships.

ADA 2022 Scientific Sessions. Abstract 257-OR. Presented June 6, 2022.

Mitchel L. Zoler is a reporter for Medscape and MDedge based in the Philadelphia area. @mitchelzoler

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