MON-LB115 Ready-To-Use Glucagon for the Prevention of Exercise-Induced Hypoglycemia in a Clinical Research Setting

OBJECTIVE: A mini-dose of a novel ready-to-use liquid stable glucagon (RTUG; Xeris Pharmaceuticals) was evaluated for the prevention of exercise-induced hypoglycemia (EIH) during and after moderate-to-high intensity aerobic exercise, in both a clinical research center (CRC) and outpatient setting. The observations from the CRC setting are reported here. METHOD: A Phase 2 randomized, placebo-controlled, double-blind, two-treatment, crossover study enrolled 48 adults with Type 1 diabetes (T1D) treated with continuous subcutaneous insulin infusion, to evaluate the efficacy of pre-exercise RTUG in addition to standard of care basal insulin rate reduction. The CRC setting included 2 separate daytime exercise sessions 2 to 28 days apart. At 5 minutes prior to each exercise session, subjects reduced their basal rate of insulin infusion by 50% and self-administered placebo or RTUG 150 micrograms (μg) before performing 45 minutes of moderate-to-high intensity, aerobic exercise with a target of 80% maximum heart rate. Blood glucose was measured before, during, and after exercise to evaluate the incidence and severity of hypoglycemia. RESULT: Of the 45 subjects (93.8%) that completed both exercise sessions in the CRC, EIH occurred more in placebo (n=8) compared to RTUG (n=1). More subjects used glucose tablets to treat EIH in placebo (n=4) compared to RTUG (n=1). Placebo-treated participants consumed 7-fold greater glucose tablets during and after exercise, and experienced more episodes of post-exercise hyperglycemia (blood glucose >250 mg/dL), compared to RTUG. Treatment emergent adverse events with RTUG were comparable to placebo. RTUG 150 μg caused no edema, erythema, nor injection site reactions. RTUG was safe and well tolerated and no serious adverse events occurred. CONCLUSION:RTUG 150 μg adequately maintained euglycemia during and following prolonged, continuous, moderate-to-high intense aerobic exercise in the controlled CRC setting. When used prior to moderate-to-high intensity aerobic exercise, RTUG may reduce exercise-induced hypoglycemia in adults with T1D. These findings support the continued evaluation in the outpatient setting.