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- Title
A Randomized, Placebo-Controlled Double-Blind Trial of a Closed-Loop Glucagon System for Postbariatric Hypoglycemia.
- Authors
Mulla, Christopher M; Zavitsanou, Stamatina; Laguna Sanz, Alejandro Jose; Pober, David; Richardson, Lauren; Walcott, Pamela; Arora, Ipsa; Newswanger, Brett; Cummins, Martin J; Prestrelski, Steve J; Doyle, Francis J; Dassau, Eyal; Patti, Mary Elizabeth
- Abstract
<bold>Background: </bold>Postbariatric hypoglycemia (PBH) can threaten safety and reduce quality of life. Current therapies are incompletely effective.<bold>Methods: </bold>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 2 study visits. The system delivered up to 2 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.<bold>Results: </bold>Twelve participants (11 females/1 male, age 52 ± 2, 8 ± 1 years postsurgery, mean ± SEM) completed all visits. Predictive hypoglycemia alerts prompted automated drug delivery postmeal, when sensor glucose was 114 ± 7 vs 121 ± 5 mg/dL (P = .39). Seven participants required rescue glucose after vehicle but not glucagon (P = .008). Five participants had severe hypoglycemia (<55 mg/dL) after vehicle but not glucagon (P = .03). Nadir plasma glucose was higher with glucagon vs vehicle (67 ± 3 vs 59 ± 2 mg/dL, P = .004). Plasma glucagon rose after glucagon delivery (1231 ± 187 vs 16 ± 1 pg/mL at 30 minutes, P = .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.<bold>Conclusion: </bold>A CGM-guided closed-loop rescue system can detect imminent hypoglycemia and deliver glucagon, reducing severe hypoglycemia in PBH.<bold>Clinical Trials Registration: </bold>NCT03255629.
- Subjects
CLOSED loop systems; HYPOGLYCEMIA; ARTIFICIAL pancreases; GLUCOSE analysis; GLUCAGON; CROSSOVER trials; GLYCOPYRROLATE
- Publication
Journal of Clinical Endocrinology & Metabolism, 2019, pN.PAG
- ISSN
0021-972X
- Publication type
journal article
- DOI
10.1210/clinem/dgz197