Safety and Performance of an Advanced Hybrid Closed-Loop (AHCL) Algorithm with Ultra-rapid Lispro (URLi) and Lispro

Tuning a multi-model predictive control AHCL algorithm to the PK/PD properties of URLi may result in improved performance vs Lispro with no increased safety concerns. This was a randomized, double-blind, inpatient, 2-period crossover study in 22 adults with T1D on insulin pumps. Each URLi and Lispro treatment period had a 4-day inpatient visit with insulin doses calculated using the tuned AHCL algorithm. To challenge the algorithm, tests included unannounced exercise, 1 hr delayed bolus, underbolus, and overbolus. Participants (59% male) had mean ±SD age 43.4±13.77 years, T1D duration 25.9±9.61 yrs, and HbA1c 7.6±0.47%. Mean time in range (TIR; 70-180 mg/dL) during the overall inpatient period: URLi 79.4%; Lispro 78.7 % (p=0.80) with a trend towards decreased time <70 mg/dl (1.5 vs 2.4, p=0.08) for URLi. URLi had a significant difference in Level 1 hypoglycemia (30 vs 55 events, p = 0.01) but not Level 2 (4 vs 9 events, p=0.3). TIRs were similar including during meal/challenge periods (Table) with a trend towards greater TIR during the postprandial period and reduced time <70 mg/dl during exercise for URLi. There was greater TIR during overbolus with Lispro. No severe hypoglycemia events occurred. Results suggest reduced hypoglycemia with URLi vs Lispro with comparable glycemic control. The AHCL algorithm showed promising glycemic performance in a supervised setting when used with URLi or Lispro. Disclosure R. Pollom: None. E. Dassau: Employee; Eli Lilly and Company, Stock/Shareholder; Eli Lilly and Company. M. Katz: Employee; Eli Lilly and Company, Stock/Shareholder; Eli Lilly and Company. L. Nosek: None. H. Coester: None. E. Zijlstra: Other Relationship; Eli Lilly and Company, Speaker's Bureau; Gan & Lee Pharmaceuticals, Novo Nordisk A/S. A. Ghosh: None. A. Haidar: Consultant; Eli Lilly and Company, Other Relationship; Bigfoot Biomedical, Inc., Research Support; Adocia, Dexcom, Inc., Tandem Diabetes Care, Inc. R. Jones: Employee; Eli Lilly and Company, Stock/Shareholder; Eli Lilly and Company. J. Leohr: None. S. E. Gleissner: None.