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

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 mg dasiglucagon (D-80), or 120 mg dasiglucagon (D-120) 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 D-80, and in 4 after D-120 (CHO vs. D-80, P=0.096; CHO vs. D-120, P=0.034). Time spent in hypoglycemia (<3.9 mmol/L [70 mg/dL]) was 14%, 7%, and 6% for CHO, D-80, and D-120, 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, D-80, and D-120, respectively (CHO vs. D-80, P=0.006; CHO vs. D-120, 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.