Dasiglucagon: A Next-Generation Glucagon Analog for Rapid and Effective Treatment of Severe Hypoglycemia Results of Phase 3 Randomized Double-Blind Clinical Trial

OBJECTIVE To evaluate the efficacy and safety of dasiglucagon – a ready-to-use, next-generation glucagon analog in aqueous formulation for subcutaneous dosing – for treatment of severe hypoglycemia in adults with type 1 diabetes. RESEARCH DESIGN AND METHODS This randomized, double-blind trial included 170 adult participants with type 1 diabetes, each randomized to receive a single subcutaneous dose of dasiglucagon 0.6 mg, placebo, or reconstituted glucagon 1 mg (2:1:1 randomization) during controlled insulin-induced hypoglycemia. The primary endpoint was time to plasma glucose recovery, defined as an increase of ≥20 mg/dL from baseline without rescue intravenous glucose. The primary comparison was dasiglucagon versus placebo; reconstituted lyophilized glucagon was included as reference. RESULTS Median (95% CI) time to recovery was 10 (10, 10) minutes for dasiglucagon compared to 40 (30, 40) minutes for placebo (P<0.001); the corresponding result for reconstituted glucagon was 12 (10, 12) minutes. In the dasiglucagon group, plasma glucose recovery was achieved within 15 minutes in all but one participant (99%), superior to placebo (2%; P<0.001) and similar to glucagon (95%). Similar outcomes were observed for the other investigated time points at 10, 20 and 30 minutes after dosing. The most frequent side effects were nausea and vomiting, as expected for glucagon treatment. CONCLUSIONS Dasiglucagon provided rapid and effective reversal of hypoglycemia in adults with type 1 diabetes, with safety and tolerability similar to that reported for reconstituted glucagon injection. The ready-to-use, aqueous formulation of dasiglucagon offers the potential to provide a rapid and reliable treatment for severe hypoglycemia.

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Randomized, double‐blind clinical trial comparing basal insulin peglispro and insulin glargine, in combination with prandial insulin lispro, in patients with type 1 diabetes: IMAGINE 3

Diabetes Obesity and Metabolism ◽

10.1111/dom.12698 ◽

2016 ◽

Vol 18 (11) ◽

pp. 1081-1088 ◽

Cited By ~ 29

Author(s):

R. M. Bergenstal ◽

H. Lunt ◽

E. Franek ◽

F. Travert ◽

J. Mou ◽

...

Keyword(s):

Clinical Trial ◽

Type 1 Diabetes ◽

Insulin Glargine ◽

Insulin Lispro ◽

Basal Insulin ◽

Double Blind ◽

Prandial Insulin ◽

Double Blind Clinical Trial

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Dasiglucagon, a next‐generation ready‐to‐use glucagon analog, for treatment of severe hypoglycemia in children and adolescents with type 1 diabetes: results of a phase 3, randomized controlled trial

Pediatric Diabetes ◽

10.1111/pedi.13220 ◽

2021 ◽

Author(s):

Tadej Battelino ◽

Ramin Tehranchi ◽

Timothy Bailey ◽

Klemen Dovc ◽

Anita Melgaard ◽

...

Keyword(s):

Randomized Controlled Trial ◽

Type 1 Diabetes ◽

Children And Adolescents ◽

Controlled Trial ◽

Severe Hypoglycemia ◽

Next Generation ◽

Phase 3 ◽

Randomized Controlled

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Dasiglucagon: A Next-Generation Glucagon Analog for Rapid and Effective Treatment of Severe Hypoglycemia Results of Phase 3 Randomized Double-Blind Clinical Trial

Diabetes Care ◽

10.2337/dc20-2995 ◽

2021 ◽

pp. dc202995

Author(s):

Thomas R. Pieber ◽

Ronnie Aronson ◽

Ulrike Hövelmann ◽

Julie Willard ◽

Leona Plum-Mörschel ◽

...

Keyword(s):

Clinical Trial ◽

Effective Treatment ◽

Severe Hypoglycemia ◽

Next Generation ◽

Phase 3 ◽

Double Blind ◽

Double Blind Clinical Trial

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131-OR: ADA Presidents’ Select Abstract: Effect of Insulin Degludec vs. Insulin Glargine U100 on Occurrence of Nocturnal Hypoglycemia Assessed by Nocturnal Plasma Glucose Profiles in People with Type 1 Diabetes Prone to Nocturnal Severe Hypoglycemia

Diabetes ◽

10.2337/db21-131-or ◽

2021 ◽

Vol 70 (Supplement 1) ◽

pp. 131-OR

Author(s):

JULIE M. BRØSEN ◽

RIKKE AGESEN ◽

PETER L. KRISTENSEN ◽

SR., AMRA CIRIC ALIBEGOVIC ◽

HENRIK U. ANDERSEN ◽

...

Keyword(s):

Type 1 Diabetes ◽

Insulin Glargine ◽

Plasma Glucose ◽

Severe Hypoglycemia ◽

Insulin Degludec ◽

Nocturnal Hypoglycemia ◽

Select Abstract ◽

Glucose Profiles

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Efficacy and safety of insulin glargine 300 U/mL (Gla-300) vs insulin glargine 100 U/mL (Gla-100) in children and adolescents (6–17 years) with type 1 diabetes: results of the EDITION JUNIOR randomized controlled trial

10.2337/figshare.12174711.v1 ◽

2020 ◽

Author(s):

Thomas Danne ◽

William V. Tamborlane ◽

Oleg A. Malievsky ◽

Denise R. Franco ◽

Tomoyuki Kawamura ◽

...

Keyword(s):

Type 1 Diabetes ◽

Insulin Glargine ◽

Children And Adolescents ◽

Plasma Glucose ◽

Therapeutic Option ◽

Controlled Trial ◽

Severe Hypoglycemia ◽

Efficacy And Safety ◽

Open Label

<a>Objective: To compare efficacy and safety of insulin glargine 300 U/mL (Gla-300) and 100 U/mL (Gla-100) in children and adolescents (6–17 years) with type 1 diabetes.</a> Study Design: EDITION JUNIOR was a non-inferiority, international, open-label, two-arm, parallel-group, phase 3b trial. Participants were randomized 1:1 to Gla-300 or Gla-100, titrated to achieve fasting self-monitored plasma glucose levels of 90–130 mg/dL (5.0–7.2 mmol/L), with continuation of prior prandial insulin. The primary endpoint was between-group difference in HbA1c change from baseline to Week 26. Other assessments included change in fasting plasma glucose (FPG), hypoglycemia, hyperglycemia with ketosis and adverse events. Results: In 463 randomized participants (Gla-300, n=233; Gla-100, n=230), comparable least squares (LS) mean (standard error) reductions in HbA1c were observed from baseline to Week 26 (−0.40 [0.06] % for both), with LS mean between-group difference of 0.004 % (95% CI: −0.17–0.18), confirming non-inferiority at the prespecified 0.3 % (3.3 mmol/mol) margin. Mean FPG change from baseline to Week 26 was also similar between groups. During the 6-month treatment period, incidence and event rates of severe or documented (≤70 mg/dL [≤3.9 mmol/L]) hypoglycemia were similar between groups. Incidence of severe hypoglycemia was 6.0% with Gla-300 and 8.8% with Gla-100 (relative risk 0.68 [95% CI: 0.35–1.30]). Incidence of any hyperglycemia with ketosis was 6.4% with Gla-300, 11.8% with Gla-100. Conclusions: Gla-300 provided similar glycemic control and safety profiles to Gla-100 in children and adolescents with type 1 diabetes, indicating that Gla-300 is a suitable therapeutic option in this population.

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Efficacy and safety of insulin glargine 300 U/mL (Gla-300) vs insulin glargine 100 U/mL (Gla-100) in children and adolescents (6–17 years) with type 1 diabetes: results of the EDITION JUNIOR randomized controlled trial

10.2337/figshare.12174711 ◽

2020 ◽

Author(s):

Thomas Danne ◽

William V. Tamborlane ◽

Oleg A. Malievsky ◽

Denise R. Franco ◽

Tomoyuki Kawamura ◽

...

Keyword(s):

Type 1 Diabetes ◽

Insulin Glargine ◽

Children And Adolescents ◽

Plasma Glucose ◽

Therapeutic Option ◽

Controlled Trial ◽

Severe Hypoglycemia ◽

Efficacy And Safety ◽

Open Label

<a>Objective: To compare efficacy and safety of insulin glargine 300 U/mL (Gla-300) and 100 U/mL (Gla-100) in children and adolescents (6–17 years) with type 1 diabetes.</a> Study Design: EDITION JUNIOR was a non-inferiority, international, open-label, two-arm, parallel-group, phase 3b trial. Participants were randomized 1:1 to Gla-300 or Gla-100, titrated to achieve fasting self-monitored plasma glucose levels of 90–130 mg/dL (5.0–7.2 mmol/L), with continuation of prior prandial insulin. The primary endpoint was between-group difference in HbA1c change from baseline to Week 26. Other assessments included change in fasting plasma glucose (FPG), hypoglycemia, hyperglycemia with ketosis and adverse events. Results: In 463 randomized participants (Gla-300, n=233; Gla-100, n=230), comparable least squares (LS) mean (standard error) reductions in HbA1c were observed from baseline to Week 26 (−0.40 [0.06] % for both), with LS mean between-group difference of 0.004 % (95% CI: −0.17–0.18), confirming non-inferiority at the prespecified 0.3 % (3.3 mmol/mol) margin. Mean FPG change from baseline to Week 26 was also similar between groups. During the 6-month treatment period, incidence and event rates of severe or documented (≤70 mg/dL [≤3.9 mmol/L]) hypoglycemia were similar between groups. Incidence of severe hypoglycemia was 6.0% with Gla-300 and 8.8% with Gla-100 (relative risk 0.68 [95% CI: 0.35–1.30]). Incidence of any hyperglycemia with ketosis was 6.4% with Gla-300, 11.8% with Gla-100. Conclusions: Gla-300 provided similar glycemic control and safety profiles to Gla-100 in children and adolescents with type 1 diabetes, indicating that Gla-300 is a suitable therapeutic option in this population.

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