ABSTRACT
OBJECTIVE: To demonstrate bioequivalence and safety for a ready-to-use room-temperature liquid-stable glucagon administered subcutaneously (SC) through a glucagon autoinjector (GAI) or a glucagon vial and syringe kit (GVS), versus a glucagon prefilled syringe (G-PFS). METHODS: Healthy adults (N = 32) were randomly assigned to receive 1-mg glucagon as GAI or G-PFS, and then as the alternative three to seven days later. Other healthy adults (N = 40) were randomly assigned to receive 1-mg glucagon as GVS or G-PFS, and then as the alternative two days later. Samples for plasma glucagon were obtained through 240 minutes after glucagon injection. Bioequivalence was declared when the geometric mean estimate ratio of the area under-the-concentration-versus-time curve from 0 to 240 minutes (AUC0-240) and maximum concentration (Cmax) for plasma glucagon between treatment groups was contained within the bounds of 80% and 125%. Adverse events (AEs) were recorded. RESULTS: The 90% confidence intervals (CIs) for AUC0-240 and Cmax geometric mean ratios for G-PFS to GAI and GVS to G-PFS were contained within the bounds 80% to 125% (G-PFS:GAI AUC0-240 95.05%, 119.67% and Cmax 88.01%, 120.24%; GVS:G-PFS AUC0-240 87.39%, 100.66% and Cmax 89.08%, 106.08%). At least one AE occurred in 15.6% (5/32) participants with GAI, 25% (18/72) with G-PFS, and 32.5% (13/40) with GVS. Sixty-nine of 73 (94.5%) AEs were mild, and none were serious. Nausea was the most common (33/73 [45%]). CONCLUSIONS: Bioequivalence and safety were established after 1 mg of this ready-to-use room-temperature liquid-stable glucagon, administered SC to healthy adults, by autoinjector, prefilled syringe, or vial and syringe kit.
ABSTRACT
OBJECTIVE: To determine effect of mini-dose, ready-to-use glucagon on incidence of exercise-associated hypoglycemia (EAH) in adults with type 1 diabetes. RESEARCH DESIGN AND METHODS: Individuals initially participated in the in-clinic training phase for which they were randomly assigned to a crossover design: 150 µg glucagon (treatment arm A) or placebo (arm B) subcutaneously, immediately before exercise, plus 50% reduction in continuous subcutaneous insulin infusion (CSII) basal delivery rate. Completers were then rerandomly assigned in the 12-week outpatient investigational phase: arm A, B, or open-label C, 150 µg glucagon alone. Participants were to undertake their usual aerobic exercise at moderate to high intensity for 30 to 75 min in real-world settings. Data were analyzed for incidence of level 1 hypoglycemia based on self-monitoring blood glucose and for various secondary and exploratory end points. RESULTS: Of 48 participants who completed the training phase, 45 continued to the outpatient phase. For all exercise sessions in the outpatient phase (n = 795), incidence of level 1 hypoglycemia was lower in both glucagon arms (A, 12% [P < 0.0001]; C, 16% [P = 0.0032]) than in the placebo arm (B, 39%). Times below range, in range, and above range from 0 to 300 min did not significantly differ among treatment arms. Consumed grams of exercise carbohydrates were lower with glucagon use than with placebo use but did not reach statistical significance (P = 0.12). Adverse events were similar among treatment arms. CONCLUSIONS: Mini-dose glucagon with or without 50% reduction in CSII basal delivery rate may help to decrease EAH incidence in adults with type 1 diabetes.
