Dual-hormone closed loop system using a liquid stable glucagon formulation versus insulin-only closed loop system compared to a predictive low glucose suspend system: an open label, outpatient, single center, crossover, randomized control trial

Objective: To assess the efficacy and feasibility of a dual-hormone 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 system.

Research Design and Methods: In a 76-hour, 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) predictive low glucose suspend (PLGS). The primary endpoint was percent time in hypoglycemia (<70 mg/dL) from start of in-clinic aerobic exercise (45mins at 60% VO_2max) to 4 hours after.

Results: DH reduced hypoglycemia compared with SH during and after exercise (DH 0.0% [0.0-4.2], SH 8.3% [0.0-12.5], p=0.025). There was an increased time in hyperglycemia (>180mg/dL) during and after exercise for DH vs 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, 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 versus 25.1% for SH (p=0.044) and 34.7% for PLGS (p=0.140). Four participants experienced nausea related to glucagon leading 3 to withdraw from the study.

Conclusions: The glucagon formulation demonstrated feasibility in a closed loop system. The dual-hormone system reduced hypoglycemia during and after exercise with some increase in hyperglycemia.