Low-Dose Dasiglucagon Versus Oral Glucose for Prevention of Insulin-Induced Hypoglycemia in People With Type 1 Diabetes: A Phase 2, Randomized, Three-Arm Crossover Study

Diabetes Care. 2022 Jun 2;45(6):1391-1399. doi: 10.2337/dc21-2304.

Abstract

Objective: To compare the efficacy of low-dose subcutaneous dasiglucagon with oral glucose for prevention of insulin-induced hypoglycemia in people with type 1 diabetes.

Research design and methods: Twenty adults with type 1 diabetes using multiple daily injection or insulin pump therapy completed a phase 2, randomized, three-arm crossover study. On each study visit, an individualized subcutaneous insulin bolus was administered aiming for a plasma glucose (PG) concentration of 3.0 mmol/L (54 mg/dL). When a PG concentration of 4.5 mmol/L (81 mg/dL) was reached, 15 g oral glucose (CHO) from dextrose tablets, 80 µg dasiglucagon (D80), or 120 µg dasiglucagon (D120) was administered. PG was measured frequently for the following 180 min.

Results: Hypoglycemia (<3.9 mmol/L [70 mg/dL]) occurred in 10 participants after CHO, in 5 after D80, and in 4 after D120 (CHO vs. D80, P = 0.096; CHO vs. D120, P = 0.034). Time spent in hypoglycemia (<3.9 mmol/L [70 mg/dL]) was 14%, 7%, and 6% for CHO, D80, and D120, respectively (P = 0.273). The median time (95% CI) from intervention to first increase in PG of 1.1 mmol/L (20 mg/dL) was 30 (25-50), 15 (15-20), and 15 (15-20) minutes for CHO, D80, and D120, respectively (CHO vs. D80, P = 0.006; CHO vs. D120, P = 0.003). Episodes of nausea were numerically, but not significantly, higher after dasiglucagon administration. No significant differences in visual analog scale-assessed adverse effects were observed between interventions.

Conclusions: Low-dose dasiglucagon safely and effectively prevented insulin-induced hypoglycemia with a faster glucose-elevating profile than oral glucose.

Trial registration: ClinicalTrials.gov NCT04449692.

Publication types

  • Clinical Trial, Phase II
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Blood Glucose
  • Cross-Over Studies
  • Diabetes Mellitus, Type 1*
  • Glucagon / analogs & derivatives
  • Humans
  • Hypoglycemia* / chemically induced
  • Hypoglycemia* / prevention & control
  • Hypoglycemic Agents / adverse effects
  • Insulin / adverse effects

Substances

  • Blood Glucose
  • Hypoglycemic Agents
  • Insulin
  • dasiglucagon
  • Glucagon

Associated data

  • ClinicalTrials.gov/NCT04449692
  • figshare/10.2337/figshare.19403831