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      A Randomized, Placebo-Controlled Double-Blind Trial of a Closed-Loop Glucagon System for Post-Bariatric Hypoglycemia

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          Abstract

          Background

          Post-bariatric hypoglycemia (PBH) can threaten safety and reduce quality of life. Current therapies are incompletely effective.

          Methods

          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.

          Findings

          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.

          Interpretation

          A CGM-guided closed-loop rescue system can detect imminent hypoglycemia and deliver glucagon, reducing severe hypoglycemia in PBH.

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          Author and article information

          Journal
          The Journal of Clinical Endocrinology & Metabolism
          The Endocrine Society
          0021-972X
          1945-7197
          November 12 2019
          Affiliations
          [1 ]Research Division, Joslin Diabetes Center
          [2 ]Harvard John A. Paulson School of Engineering and Applied Sciences, Harvard University
          [3 ]Xeris Pharmaceuticals, Inc
          Article
          10.1210/clinem/dgz197
          7174034
          31714583
          52b430d6-ab12-4616-823b-68e954884352
          © 2019

          https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model

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