TY - JOUR
T1 - 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
T2 - An open-label, outpatient, single-center, crossover, randomized controlled trial
AU - Wilson, Leah M.
AU - Jacobs, Peter G.
AU - Ramsey, Katrina L.
AU - Resalat, Navid
AU - Reddy, Ravi
AU - Branigan, Deborah
AU - Leitschuh, Joseph
AU - Gabo, Virginia
AU - Guillot, Florian
AU - Senf, Brian
AU - El Youssef, Joseph
AU - Steineck, Isabelle Isa Kristin
AU - Tyler, Nichole S.
AU - Castle, Jessica R.
N1 - Funding Information:
was sponsored by Xeris Pharmaceuticals via a subaward from JDRF (Industry Discovery & Development Partnerships grant #15-2013-505). P.G.J. and J.R.C. have a financial interest in Pacific Diabetes Technologies, Inc., a company that may have a commercial interest in the results of this type of research and technology. This potential conflict of interest has been reviewed and man-agedbyOHSU.Inaddition,P.G.J.andJ.R.C.report research support from Xeris, Dexcom, and Tandem Diabetes Care. J.R.C. reports advisory board participation for Zealand Pharma, Novo Nordisk, and AstraZeneca, consulting for Dexcom, and a U.S. patent on the use of ferulic acid to stabilize glucagon. No other potential conflicts of interest relevant to the article were reported.
Funding Information:
This study was sponsored by Xeris Pharmaceuticals via a subaward from JDRF (Industry Discovery & Development Partnerships grant #15-2013-505). P.G.J. and J.R.C. have a financial interest in Pacific Diabetes Technologies, Inc., a company that may have a commercial interest in the results of this type of research and technology. This potential conflict of interest has been reviewed and managed by OHSU. In addition, P.G.J. and J.R.C. report research support from Xeris, Dexcom, and Tandem Diabetes Care. J.R.C. reports advisory board participation for Zealand Pharma, Novo Nordisk, and AstraZeneca, consulting for Dexcom, and a U.S. patent on the use of ferulic acid to stabilize glucagon. No other potential conflicts of interest relevant to the article were reported. The funder of the study had no role in the study design, data collection, data analysis, data interpretation, or writing of the report.
Publisher Copyright:
© 2020 by the American Diabetes Association.
PY - 2020/11
Y1 - 2020/11
N2 - 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 5 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 5 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 5 0.044). For the entire study duration, DH had 28.2% time in hyperglycemia vs. 25.1% for SH (P 5 0.044) and 34.7% for PLGS (P 5 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.
AB - 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 5 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 5 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 5 0.044). For the entire study duration, DH had 28.2% time in hyperglycemia vs. 25.1% for SH (P 5 0.044) and 34.7% for PLGS (P 5 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.
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U2 - 10.2337/dc19-2267
DO - 10.2337/dc19-2267
M3 - Article
C2 - 32907828
AN - SCOPUS:85093967814
SN - 1935-5548
VL - 43
SP - 2721
EP - 2729
JO - Diabetes Care
JF - Diabetes Care
IS - 11
ER -