Dual-Hormone Closed-Loop System Using a Liquid Stable Glucagon Formulation Versus Insulin-Only Closed-Loop System Compared With a Predictive Low Glucose Suspend System: An Open-Label, Outpatient, Single-Center, Crossover, Randomized Controlled Trial (original) (raw)

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Emerging Therapies: Drugs and Regimens| September 09 2020

Leah M. Wilson

;

1Harold Schnitzer Diabetes Health Center, Division of Endocrinology, Oregon Health & Science University, Portland, OR

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Peter G. Jacobs

;

2Artificial Intelligence for Medical Systems (AIMS) Lab, Department of Biomedical Engineering, Oregon Health & Science University, Portland, OR

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Katrina L. Ramsey;

3Oregon Clinical and Translational Research Institute Biostatistics and Design Program, Oregon Health & Science University & Portland State University School of Public Health, Portland, OR

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Navid Resalat;

2Artificial Intelligence for Medical Systems (AIMS) Lab, Department of Biomedical Engineering, Oregon Health & Science University, Portland, OR

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Ravi Reddy;

2Artificial Intelligence for Medical Systems (AIMS) Lab, Department of Biomedical Engineering, Oregon Health & Science University, Portland, OR

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Deborah Branigan;

1Harold Schnitzer Diabetes Health Center, Division of Endocrinology, Oregon Health & Science University, Portland, OR

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Joseph Leitschuh;

2Artificial Intelligence for Medical Systems (AIMS) Lab, Department of Biomedical Engineering, Oregon Health & Science University, Portland, OR

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Virginia Gabo;

1Harold Schnitzer Diabetes Health Center, Division of Endocrinology, Oregon Health & Science University, Portland, OR

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Florian Guillot;

1Harold Schnitzer Diabetes Health Center, Division of Endocrinology, Oregon Health & Science University, Portland, OR

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Brian Senf;

1Harold Schnitzer Diabetes Health Center, Division of Endocrinology, Oregon Health & Science University, Portland, OR

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Joseph El Youssef;

1Harold Schnitzer Diabetes Health Center, Division of Endocrinology, Oregon Health & Science University, Portland, OR

2Artificial Intelligence for Medical Systems (AIMS) Lab, Department of Biomedical Engineering, Oregon Health & Science University, Portland, OR

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Isabelle Isa Kristin Steineck

;

Isabelle Isa Kristin Steineck

4Steno Diabetes Center Copenhagen, Gentofte, Denmark

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Nichole S. Tyler;

2Artificial Intelligence for Medical Systems (AIMS) Lab, Department of Biomedical Engineering, Oregon Health & Science University, Portland, OR

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Jessica R. Castle

1Harold Schnitzer Diabetes Health Center, Division of Endocrinology, Oregon Health & Science University, Portland, OR

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Diabetes Care 2020;43(11):2721–2729

Citation

Leah M. Wilson, Peter G. Jacobs, Katrina L. Ramsey, Navid Resalat, Ravi Reddy, Deborah Branigan, Joseph Leitschuh, Virginia Gabo, Florian Guillot, Brian Senf, Joseph El Youssef, Isabelle Isa Kristin Steineck, Nichole S. Tyler, Jessica R. Castle; Dual-Hormone Closed-Loop System Using a Liquid Stable Glucagon Formulation Versus Insulin-Only Closed-Loop System Compared With a Predictive Low Glucose Suspend System: An Open-Label, Outpatient, Single-Center, Crossover, Randomized Controlled Trial. _Diabetes Care 1 November 2020; 43 (11): 2721–2729. https://doi.org/10.2337/dc19-2267

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OBJECTIVE

To assess the efficacy and feasibility of a dual-hormone (DH) closed-loop system with insulin and a novel liquid stable glucagon formulation compared with an insulin-only closed-loop system and a predictive low glucose suspend (PLGS) system.

RESEARCH DESIGN AND METHODS

In a 76-h, randomized, crossover, outpatient study, 23 participants with type 1 diabetes used three modes of the Oregon Artificial Pancreas system: 1) dual-hormone (DH) closed-loop control, 2) insulin-only single-hormone (SH) closed-loop control, and 3) PLGS system. The primary end point was percentage time in hypoglycemia (<70 mg/dL) from the start of in-clinic aerobic exercise (45 min at 60% VO2max) to 4 h after.

RESULTS

DH reduced hypoglycemia compared with SH during and after exercise (DH 0.0% [interquartile range 0.0–4.2], SH 8.3% [0.0–12.5], P = 0.025). There was an increased time in hyperglycemia (>180 mg/dL) during and after exercise for DH versus SH (20.8% DH vs. 6.3% SH, P = 0.038). Mean glucose during the entire study duration was DH, 159.2; SH, 151.6; and PLGS, 163.6 mg/dL. Across the entire study duration, DH resulted in 7.5% more time in target range (70–180 mg/dL) compared with the PLGS system (71.0% vs. 63.4%, P = 0.044). For the entire study duration, DH had 28.2% time in hyperglycemia vs. 25.1% for SH (P = 0.044) and 34.7% for PLGS (P = 0.140). Four participants experienced nausea related to glucagon, leading three to withdraw from the study.

CONCLUSIONS

The glucagon formulation demonstrated feasibility in a closed-loop system. The DH system reduced hypoglycemia during and after exercise, with some increase in hyperglycemia.

L.M.W. and P.G.J. share co-first authorship.

© 2020 by the American Diabetes Association

2020

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