1260-OR: Fully Closed-Loop Delivery of Ultra-Rapid Insulin Lispro and Pramlintide vs. Carbohydrate Counting in Type 1 Diabetes: A Randomized, Crossover, Noninferiority Trial

Introduction and Objective: Carbohydrate counting remains a major burden in type 1 diabetes. We evaluated a novel fully closed-loop (FCL) insulin-and-pramlintide delivery system designed to eliminate carbohydrate counting. Methods: We conducted a randomized, crossover, noninferiority trial assessing 21 days of (i) hybrid closed-loop (HCL) insulin-and-placebo delivery with carbohydrate counting and FCL insulin-and-pramlintide delivery at (ii) an 8 µg/U ratio and (iii) 10 µg/U ratio in adults with type 1 diabetes. Ultra-rapid insulin lispro was used in all interventions. The primary outcome was time spent in the target glucose range (70-180 mg/dL), with a 5% noninferiority margin. Results: 26 participants completed the study (18 female, 35 (SD 15) years, HbA1c 7.2% (0.7)). Mean time in target range was 72.1% (SD 11.2) with HCL insulin-and-placebo, 71.1% (10.6) with FCL insulin-and-pramlintide 8 µg/U, and 71.2% (10.2) with FCL insulin-and-pramlintide 10 µg/U. Noninferiority was not achieved for either comparison (placebo vs. pramlintide 8 µg/U: p=0.0787; placebo vs. pramlintide 10 µg/U: p=0.0584). Median time below 3.9 mmol/L was low across all interventions (placebo: 0.9%; pramlintide 8 µg/U: 1.1%; pramlintide 10 µg/U: 1.4%). Total daily insulin dose decreased from 47.4 U (IQR 38.1-66.1) with placebo to 42.8 U (36.5-59.1) with pramlintide 8 µg/U (p<0.001) and 41.3 U (34.8-56.8) with pramlintide 10 µg/U (p<0.001). Gastrointestinal events occurred only during pramlintide interventions (8 µg/U: 6 (22%) mild, 1 (4%) moderate; 10 µg/U: 7 (26%) mild, 1 (4%) moderate). No episodes of severe hypoglycemia or diabetic ketoacidosis occurred. Conclusion: Fully automated insulin-and-pramlintide delivery achieved similar glycemic outcomes to HCL therapy with carbohydrate counting, though threshold of statistical noninferiority was not met. Disclosure J. Doumat: None. M. Tsoukas: Speaker's Bureau; Current; Novo Nordisk, Eli Lilly and Company, Abbott, Janssen Pharmaceuticals, Inc., Boehringer Ingelheim International GmbH. M. Pasqua: Speaker's Bureau; Ended; Sanofi, Medtronic, Abbott Diabetes. L. Legault: Research Support; Current; Novo Nordisk. Advisory Panel; Ended; Novo Nordisk Canada Inc. Advisory Panel; Current; Ypsomed AG. Speaker's Bureau; Current; Ypsomed AG. N. Garfield: None. G. Kemp: None. M. Odabassian: None. A. Haidar: Consultant; Current; Eli Lilly and Company, Abbott Diabetes. Research Support; Ended; Beta Bionics, Inc. Research Support; Current; Tandem Diabetes Care, Inc., Dexcom, Inc. Research Support; Ended; Ypsomed AG. Other - Speakers honorarium.; Current; SiBionics. Funding Breakthrough T1D (3-SRA-2021-1070-M-B)