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.

Abstract

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. In a 76-h, randomized, crossover, outpatient study, 23 participants with type 1 diabetes used three modes of the Oregon Artificial Pancreas system: <i>1</i>) dual-hormone (DH) closed-loop control, <i>2</i>) insulin-only single-hormone (SH) closed-loop control, and <i>3</i>) 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% VO_2max) to 4 h after. 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], <i>P</i> = 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, <i>P</i> = 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%, <i>P</i> = 0.044). For the entire study duration, DH had 28.2% time in hyperglycemia vs. 25.1% for SH (<i>P</i> = 0.044) and 34.7% for PLGS (<i>P</i> = 0.140). Four participants experienced nausea related to glucagon, leading three to withdraw from the study. The glucagon formulation demonstrated feasibility in a closed-loop system. The DH system reduced hypoglycemia during and after exercise, with some increase in hyperglycemia.