Effect of Mini-Dose Ready-to-Use Liquid Glucagon on Preventing Exercise-Associated Hypoglycemia in Adults With Type 1 Diabetes

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.

Conflict of interest statement

Duality of Interest. R.A. has received advisory fees from Sanofi, Novo Nordisk, Boehringer Ingelheim, Eli Lilly and Company, HTL-STREFA, Gilead Sciences, Merck, and Xeris Pharmaceuticals, Inc. and research funding from Novo Nordisk, AstraZeneca, Eli Lilly and Company, Zealand Pharma, Xeris Pharmaceuticals, Inc., Medpace, Kowa Pharmaceuticals, Insulet, Dexcom, and Bayer. M.C.R. has served in an advisory role for Xeris Pharmaceuticals, Inc., Zealand Pharma, Zucara Therapeutics, and Supersapiens; has received compensation as a speaker at scientific sessions, workshops, or both sponsored by Novo Nordisk, Eli Lilly and Company, Sanofi, Insulet, and Medtronic Diabetes; has received in-kind research support from Dexcom; and owns stock and shares with Supersapiens and Zucara Therapeutics. V.C. and M.K.J. are employees of Xeris Pharmaceuticals, Inc. No other potential conflicts of interest relevant to this article were reported.

© 2023 by the American Diabetes Association.

Figures

Graphical abstract

Figure 1

A: Box-and-whisker plot of the incidence rate of level 1 hypoglycemia (SMBG ≤70 mg/dL) among adults with type 1 diabetes for all exercise sessions and treatment arms (A [n = 16], B [n = 14], or C [n = 14]). B: Box-and-whisker plot of the incidence rate of level 2 hypoglycemia (SMBG <54 mg/dL) among adults with type 1 diabetes who met post hoc analysis criteria (A [n = 15], B [n = 14], or C [n = 13]). For each box, the horizontal line represents the median value and lower and upper boundaries represent 25th and 75th percentiles, respectively. Whiskers represent the extreme values that are not outliers. The circles indicate outliers. The diamond within each box represents the mean value. Incidence rate was determined by dividing the number of hypoglycemic events by the number of exercise sessions. Treatment arm A, mini-dose glucagon with 50% BRR. Treatment arm B, placebo with 50% BRR. Treatment arm C, mini-dose glucagon without BRR.