Objective: A novel ready-to-use liquid stable glucagon (RTUG; Xeris Pharmaceuticals) was evaluated for safety and efficacy in the prevention of exercise induced hypoglycemia (EIH) during and after moderate-to-high intensity aerobic exercise.
Method: A Phase 2 randomized, placebo-controlled, double-blind, clinical research center (CRC) crossover stage, followed by a 12-week 3-arm parallel Outpatient stage, enrolled 48 adults with type 1 diabetes using an insulin pump. In the outpatient stage, subjects were assigned to RTUG 150 μg plus 50% basal insulin pump reduction, or RTUG 150 μg with no insulin change, or to placebo. Blood glucose was measured by blood glucose meter before, during, and after moderate-to-high intensity, aerobic exercise to evaluate the incidence and severity of hypoglycemia. Continuous glucose monitors were utilized in the CRC and Outpatient stage.
Result: Of the 48 subjects, 45 subjects (93.8%) completed multiple exercise sessions and have entered the ongoing outpatient stage. On average, subjects were 37 (±11.2) years old with an average BMI of 26.7 (±4.6), 52.1% male and 81.3% white. In the CRC stage, the placebo group experienced more EIH (16.7% vs. 2.1%), had 7-times higher glucose tablet utilization during and after exercise, resulting in more post-exercise hyperglycemia (blood glucose >250 mg/dL). To date, no SAEs have occurred, and RTUG 150 μg caused no edema, erythema, nor injection site reactions.
Conclusion: RTUG 150 μg maintained euglycemia during prolonged, continuous, intense aerobic exercise. In the CRC stage, RTUG was more effective than insulin reduction alone, to prevent EIH, and may result in less post-exercise hyperglycemia than ingestion of carbohydrate. Data from the ongoing Outpatient stage may support the use of RTUG to prevent EIH during and after aerobic exercise in real-world settings.
R. Aronson: Consultant; Self; AstraZeneca, Becton, Dickinson and Company, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Gilead Sciences, Inc., HTL Strefa, Janssen Pharmaceuticals, Inc., Merck & Co., Inc., Novo Nordisk Inc., Sanofi. Research Support; Self; AstraZeneca, Bausch Health, Bayer Inc., Becton, Dickinson and Company, Boehringer Ingelheim (Canada) Ltd., Dexcom, Inc., Eli Lilly and Company, Insulet Corporation, Janssen Pharmaceuticals, Inc., Kowa Company, Ltd., Medpace, Novo Nordisk Inc., Sanofi, Tandem Diabetes Care, Xeris Pharmaceuticals, Inc., Zealand Pharma A/S. M. Riddell: Advisory Panel; Self; Zucara Therapeutics Inc. Consultant; Self; Lilly Diabetes. Research Support; Self; Dexcom, Inc., Insulet Corporation. Speaker’s Bureau; Self; Medtronic, Novo Nordisk A/S. M.K. Junaidi: Employee; Self; Xeris Pharmaceuticals, Inc. N.C. Close: Employee; Self; EmpiriStat, Inc. D.J. Sequeira: Employee; Self; Xeris Pharmaceuticals, Inc.