Post-bariatric hypoglycemia (PBH) can threaten safety and reduce quality of life. Current therapies are incompletely effective.
Patients with PBH were enrolled in a double-blind, placebo-controlled, crossover trial to evaluate a closed-loop glucose-responsive automated glucagon delivery system designed to reduce severe hypoglycemia. A hypoglycemia detection and mitigation algorithm was embedded in the Artificial Pancreas System connected to a continuous glucose monitor (CGM, Dexcom) driving a patch infusion pump (Insulet) filled with liquid investigational glucagon (Xeris) or placebo (vehicle). Sensor/plasma glucose responses to mixed meal were assessed during two study visits. The system delivered up to two doses of study drug (300/150 μg glucagon or equal-volume vehicle) if triggered by the algorithm. Rescue dextrose was given for plasma glucose <55 mg/dL or neuroglycopenia.
Twelve participants (11F/1M, age 52+2, 8+1 years post-surgery, mean+SEM) completed all visits. Predictive hypoglycemia alerts prompted automated drug delivery post-meal, when sensor glucose was 114+7 vs. 121+5 mg/dL (p=0.39). Seven participants required rescue glucose after vehicle but not glucagon (p=0.008). Five participants had severe hypoglycemia (<55 mg/dL) after vehicle but not glucagon (p=0.03). Nadir plasma glucose was higher with glucagon vs. vehicle (67±3 vs. 59±2 mg/dL, p=0.004). Plasma glucagon rose after glucagon delivery (1231±187 vs. 16±1 pg/mL at 30 minutes, p=0.001). No rebound hyperglycemia occurred. Transient infusion site discomfort was reported with both glucagon (n=11/12) and vehicle (n=10/12). No other adverse events were observed.